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Ageing (
BE) or aging (
AE) is the process of becoming
older
Older is the comparative form of "old".
It may also refer to:
Music:
* ''Older'' (album), the third studio album from George Michael (released in 1996)
** "Older" (George Michael song)
* "Older", a song on the 1999 album '' Long Tall Weekend'' ...
. The term refers mainly to
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
s, many other
animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
s, and
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
, whereas for example,
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
,
perennial plants
A perennial plant or simply perennial is a plant that lives more than two years. The term ('' per-'' + '' -ennial'', "through the years") is often used to differentiate a plant from shorter-lived annuals and biennials. The term is also widel ...
and some simple animals are potentially
biologically immortal. In a broader sense, ageing can refer to single cells within an organism which have
ceased dividing, or to the
population of a species.
In humans, ageing represents the accumulation of changes in a human being over time
and can encompass physical, psychological, and social changes. Reaction time, for example, may slow with age, while memories and general knowledge typically increase. Ageing increases the risk of human diseases such as
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
,
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
,
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
,
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
,
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
and
many more. Of the roughly 150,000 people who die each day across the globe, about two-thirds die from age-related causes.
Current
ageing theories are assigned to the damage concept, whereby the accumulation of damage (such as
DNA oxidation
DNA oxidation is the process of oxidative damage of deoxyribonucleic acid. As described in detail by Burrows et al., 8-oxo-2'-deoxyguanosine (8-oxo-dG) is the most common oxidative lesion observed in duplex DNA because guanine has a lower one-el ...
) may cause biological systems to fail, or to the programmed ageing concept, whereby the internal processes (epigenetic maintenance such as
DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
) inherently may cause ageing. Programmed ageing should not be confused with programmed cell death (
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
).
Obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
has been proposed to accelerate ageing, whereas dietary
calorie restriction
Calorie restriction (caloric restriction or energy restriction) is a dietary regimen that reduces intake of energy from caloric foods & beverages without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake b ...
in non-primate animals slows ageing while maintaining good health and body functions. In primates (including humans), such
life-extending effects remain uncertain.
Ageing versus immortality
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Human beings and members of other species, especially animals, age and die. Fungi, too, can age.
In contrast, many species can be considered potentially
immortal
Immortality is the ability to live forever, or eternal life.
Immortal or Immortality may also refer to:
Film
* ''The Immortals'' (1995 film), an American crime film
* ''Immortality'', an alternate title for the 1998 British film ''The Wisdom of ...
: for example,
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
fission to produce daughter cells,
strawberry
The garden strawberry (or simply strawberry; ''Fragaria × ananassa'') is a widely grown hybrid species of the genus '' Fragaria'', collectively known as the strawberries, which are cultivated worldwide for their fruit. The fruit is widely ap ...
plants grow runners to produce clones of themselves, and animals in the genus ''
Hydra'' have a regenerative ability by which they avoid dying of old age.
Early life forms on Earth, starting at least 3.7 billion years ago,
were single-celled organisms (an organism that consists of a single cell, unlike a multicellular organism that consists of multiple cells). Such organisms (
Prokaryote
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
s,
Protozoa
Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
ns,
algae
Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mic ...
) multiply by
fission into daughter cells(Daughter cells are cells that are the result of a single dividing parent cell. Two daughter cells are the result from the mitotic process while four cells are the result from the meiotic process. For organisms that reproduce via sexual reproduction, daughter cells result from meiosis); thus do not age and are potentially immortal under favorable conditions.
Ageing and mortality of the individual organism became possible with the
evolution of sexual reproduction
Sexual reproduction is an adaptive feature which is common to almost all multicellular organisms and various unicellular organisms, with some organisms being incapable of asexual reproduction. Currently the adaptive advantage of sexual reprodu ...
,
which occurred with the emergence of the fungal/animal kingdoms approximately a billion years ago, and the evolution of
seed-producing plants 320 million years ago. The sexual organism could henceforth pass on some of its genetic material to produce new individuals and could itself
become disposable with respect to the survival of its species.
This classic biological idea has however been perturbed recently by the discovery that the bacterium ''
E. coli'' may split into distinguishable daughter cells, which opens the theoretical possibility of "age classes" among bacteria.
Even within humans and other mortal species, there are cells with the potential for immortality: cancer cells which have lost the ability to die when maintained in a cell culture such as the
HeLa
HeLa (; also Hela or hela) is an immortalized cell line used in scientific research. It is the oldest and most commonly used human cell line. The line is derived from cervical cancer cells taken on February 8, 1951, named after Henrietta ...
cell line,
and specific
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
s such as
germ cell
Germ or germs may refer to:
Science
* Germ (microorganism), an informal word for a pathogen
* Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually
* Germ layer, a primary layer of cells that forms during emb ...
s (producing
ova
, abbreviated as OVA and sometimes as OAV (original animation video), are Japanese animated films and series made specially for release in home video formats without prior showings on television or in theaters, though the first part of an OVA s ...
and
spermatozoa
A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromosomes, ...
).
In artificial
cloning
Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, cl ...
, adult cells can be rejuvenated to embryonic status and then used to grow a new tissue or animal without ageing.
Normal human cells however die after about 50 cell divisions in laboratory culture (the
Hayflick Limit, discovered by
Leonard Hayflick
Leonard Hayflick (born 20 May 1928) is a Professor of Anatomy at the UCSF School of Medicine, and was Professor of Medical Microbiology at Stanford University School of Medicine. He is a past president of the Gerontological Society of America and ...
in 1961).
Signs
![Alzheimer's disease brain comparison](https://upload.wikimedia.org/wikipedia/commons/a/a5/Alzheimer%27s_disease_brain_comparison.jpg)
A number of characteristic ageing symptoms are experienced by a majority or by a significant proportion of humans during their lifetimes.
* Teenagers lose the young child's ability to
hear high-frequency sounds above 20 kHz.
*
Wrinkle
A wrinkle, also known as a rhytid, is a fold, ridge or crease in an otherwise smooth surface, such as on skin or fabric. Skin wrinkles typically appear as a result of ageing processes such as glycation, habitual sleeping positions, loss of ...
s develop mainly due to
photoageing, particularly affecting sun-exposed areas (face).
* After
peaking from the late teens to the late 20s, female fertility declines.
* After age 30 the mass of human body is decreased until 70 years and then shows damping oscillations.
* People over 35 years of age are at increasing risk for losing strength in the
ciliary muscle
The ciliary muscle is an intrinsic muscle of the eye formed as a ring of smooth muscleSchachar, Ronald A. (2012). "Anatomy and Physiology." (Chapter 4) . in the eye's middle layer, uvea ( vascular layer). It controls accommodation for viewing ...
of the eyes which leads to difficulty focusing on close objects, or
presbyopia
Presbyopia is physiological insufficiency of accommodation associated with the aging of the eye that results in progressively worsening ability to focus clearly on close objects. Also known as age-related farsightedness (or age-related long si ...
.
Most people experience
presbyopia
Presbyopia is physiological insufficiency of accommodation associated with the aging of the eye that results in progressively worsening ability to focus clearly on close objects. Also known as age-related farsightedness (or age-related long si ...
by age 45–50.
The cause is lens hardening by decreasing levels of
alpha-crystallin, a process which may be sped up by higher temperatures.
* Around age 50,
hair turns grey.
Pattern hair loss
Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ...
by the age of 50 affects about 30–50% of males and a quarter of females.
*
Menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
typically occurs between 44 and 58 years of age.
* In the 60–64 age cohort, the incidence of
osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
rises to 53%. Only 20% however report disabling osteoarthritis at this age.
* Almost half of people older than 75 have
hearing loss
Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...
(presbycusis) inhibiting spoken communication. Many vertebrates such as fish, birds and amphibians do not develop presbycusis in old age as they are able to regenerate their
cochlea
The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory org ...
r sensory cells, whereas mammals including humans have genetically lost this ability.
* By age 80, more than half of all Americans either have a
cataract
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
or have had
cataract surgery
Cataract surgery, also called lens replacement surgery, is the removal of the natural lens of the eye (also called "crystalline lens") that has developed an opacification, which is referred to as a cataract, and its replacement with an intra ...
.
*
Frailty, a syndrome of decreased strength, physical activity, physical performance and energy, affects 25% of those over 85.
Muscles have a reduced capacity of responding to exercise or injury and loss of muscle mass and strength (
sarcopenia
Sarcopenia is a type of muscle loss ( muscle atrophy) that occurs with aging and/or immobility. It is characterized by the degenerative loss of skeletal muscle mass, quality, and strength. The rate of muscle loss is dependent on exercise level, ...
) is common. Maximum oxygen utilization and maximum heart rate decline. Hand strength and mobility decrease.
*
Atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
is classified as an ageing disease.
It leads to cardiovascular disease (for example
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
and
heart attack
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
)
which globally is the most common cause of death. Vessel ageing causes vascular remodeling and loss of arterial elasticity and as a result causes the stiffness of the vasculature.
* Recent evidence suggests that age-related risk of death plateaus after age 105. The maximum human lifespan is suggested to be
115 years.
The oldest reliably recorded human was
Jeanne Calment
Jeanne Louise Calment (; 21 February 1875 – 4 August 1997) was a French supercentenarian and the oldest human whose age is documented, with a lifespan of 122 years and 164 days. Her longevity attracted media attention and medical studies ...
who died in 1997 at 122.
Dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
becomes more common with age.
About 3% of people between the ages of 65 and 74, 19% between 75 and 84, and nearly half of those over 85 years of age have dementia. The spectrum ranges from
mild cognitive impairment
Mild cognitive impairment (MCI) is a neurocognitive disorder which involves cognitive impairments beyond those expected based on an individual's age and education but which are not significant enough to interfere with instrumental activities o ...
to the neurodegenerative diseases of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
,
cerebrovascular disease
Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. Th ...
,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
and
Lou Gehrig's disease
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most com ...
. Furthermore, many types of
memory decline with ageing, but not
semantic memory
Semantic memory refers to general world knowledge that humans have accumulated throughout their lives. This general knowledge (word meanings, concepts, facts, and ideas) is intertwined in experience and dependent on culture. We can learn about n ...
or general knowledge such as vocabulary definitions, which typically increases or remains steady until late adulthood
(see
Ageing brain
Aging is a major risk factor for most common neurodegenerative diseases, including mild cognitive impairment, dementias including Alzheimer's disease, cerebrovascular disease, Parkinson's disease, and Lou Gehrig's disease. While much research has ...
).
Intelligence
Intelligence has been defined in many ways: the capacity for abstraction, logic, understanding, self-awareness, learning, emotional knowledge, reasoning, planning, creativity, critical thinking, and problem-solving. More generally, it can b ...
declines with age, though the rate varies depending on the
type and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in the rate of cognitive decline may therefore be explained in terms of people having different lengths of life.
There are changes to the brain: after 20 years of age there is a 10% reduction each decade in the total length of the brain's
myelinated
Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...
axons.
Age can result in
visual impairment
Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment ...
, whereby
non-verbal communication
Nonverbal communication (NVC) is the transmission of messages or signals through a nonverbal platform such as eye contact, facial expressions, gestures, posture, and body language. It includes the use of social cues, kinesics, distance ( prox ...
is reduced, which can lead to isolation and possible depression. Older adults, however, may not experience depression as much as younger adults, and were paradoxically found to have improved mood despite declining physical health.
Macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
causes vision loss and increases with age, affecting nearly 12% of those above the age of 80.
This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina.
Other visual diseases that often appear with age would be cataracts and glaucoma. A cataract occurs when the lens of the eye becomes cloudy making vision blurry and eventually causing blindness if untreated. They develop over time and are seen most often with those that are older. Cataracts can be treated through surgery. Glaucoma is another common visual disease that appears in older adults. Glaucoma is caused by damage to the optic nerve causing vision loss.
Glaucoma usually develops over time but there are variations to glaucoma, and some have sudden onset. There are a few procedures for glaucoma but there is no cure or fix for the damage once it has happened. Prevention is the best measure in the case of glaucoma.
A distinction can be made between "proximal ageing" (age-based effects that come about because of factors in the recent past) and "distal ageing" (age-based differences that can be traced to a cause in a person's early life, such as childhood
poliomyelitis
Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe sym ...
).
[
Ageing is among the greatest known risk factors for most human diseases.] Of the roughly 150,000 people who die each day across the globe, about two-thirds—100,000 per day—die from age-related causes. In industrialized nations, the proportion is higher, reaching 90%.
Biological basis
At present, researchers are only just beginning to understand the biological basis of ageing even in relatively simple and short-lived organisms such as yeast. Less still is known of mammalian ageing, in part due to the much longer lives of even small mammals such as the mouse (around 3 years). A model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
for the study of ageing is the nematode
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...
''C. elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
''. Thanks to its short lifespan of 2–3 weeks, our ability to easily perform genetic manipulations or to suppress gene activity with RNA interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...
, or other factors. Most known mutations and RNA interference targets that extend lifespan were first discovered in ''C. elegans''.
The factors proposed to influence biological ageing fall into two main categories, ''programmed'' and ''damage-related''. Programmed factors follow a biological timetable, perhaps one that might be a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. Damage-related factors include internal and environmental assaults to living organisms that induce cumulative damage at various levels. A third, novel, concept is that ageing is mediated by vicious cycles.
Molecular and cellular hallmarks of ageing
In a detailed review, Lopez-Otin and colleagues (2013), who discuss ageing through the lens of the damage theory, propose nine metabolic "hallmarks" of ageing in various organisms but especially mammals:
* genomic instability
Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneu ...
(mutations accumulated in nuclear DNA, in mtDNA, and in the nuclear lamina)
* telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
attrition (the authors note that artificial telomerase confers non-cancerous immortality to otherwise mortal cells)
* epigenetic alterations (including DNA methylation patterns, post-translational modification of histones, and chromatin remodelling)
* loss of proteostasis Proteostasis is the dynamic regulation of a balanced, functional proteome. The proteostasis network includes competing and integrated biological pathways within cells that control the biogenesis, folding, trafficking, and degradation of proteins ...
(protein folding and proteolysis)
* deregulated nutrient sensing (relating to the Growth hormone/Insulin-like growth factor 1 signalling pathway, which is the most conserved ageing-controlling pathway in evolution and among its targets are the FOXO
FOX (forkhead box) proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryonic ...
3/Sirtuin
Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins t ...
transcription factors and the mTOR
The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MT ...
complexes, probably responsive to caloric restriction
Calorie restriction (caloric restriction or energy restriction) is a dietary regimen that reduces intake of energy from caloric foods & beverages without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake be ...
)
* mitochondrial dysfunction (the authors point out however that a causal link between ageing and increased mitochondrial production of reactive oxygen species is no longer supported by recent research)
* cellular senescence
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approxi ...
(accumulation of no longer dividing cells in certain tissues, a process induced especially by p16INK4a
p16 (also known as p16INK4a, cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S p ...
/Rb and p19ARF/p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
to stop cancerous cells from proliferating)
* stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
exhaustion (in the authors' view caused by damage factors such as those listed above)
* altered intercellular communication (encompassing especially inflammation but possibly also other intercellular interactions
*inflammageing
Inflammaging (also known as inflamm-aging or inflamm-ageing) is a chronic, sterile low-grade inflammation that develops with advanced age, in the absence of overt infection, and may contribute to clinical manifestations of other age-related patho ...
, a chronic inflammatory phenotype in the elderly in the absence of viral infection, due to over-activation and a decrease in the precision of the innate immune system.
* dysbiosis of gut microbiome
A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably well ...
(e.g., loss of microbial diversity, expansion of enteropathogens, and altered vitamin B12 biosynthesis) is correlated with biological age rather than chronological age.
Metabolic pathways involved in ageing
There are three main metabolic pathways which can influence the rate of ageing, discussed below:
* the FOXO3
Forkhead box O3, also known as FOXO3 or FOXO3a, is a human protein encoded by the ''FOXO3'' gene.
Function
FOXO3 belongs to the O subclass of the forkhead family of transcription factors which are characterized by a distinct fork head DNA-bi ...
/Sirtuin
Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins t ...
pathway, probably responsive to caloric restriction
Calorie restriction (caloric restriction or energy restriction) is a dietary regimen that reduces intake of energy from caloric foods & beverages without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake be ...
* the Growth hormone/Insulin-like growth factor 1 signalling pathway
* the activity levels of the electron transport chain
An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
in mitochondria and (in plants) in chloroplasts.
It is likely that most of these pathways affect ageing separately, because targeting them simultaneously leads to additive increases in lifespan.
Programmed factors
The rate of ageing varies substantially across different species, and this, to a large extent, is genetically based. For example, numerous perennial plant
A perennial plant or simply perennial is a plant that lives more than two years. The term ('' per-'' + '' -ennial'', "through the years") is often used to differentiate a plant from shorter-lived annuals and biennials. The term is also wide ...
s ranging from strawberries and potatoes to willow trees
Willows, also called sallows and osiers, from the genus ''Salix'', comprise around 400 speciesMabberley, D.J. 1997. The Plant Book, Cambridge University Press #2: Cambridge. of typically deciduous trees and shrubs, found primarily on moist so ...
typically produce clones of themselves by vegetative reproduction
Vegetative reproduction (also known as vegetative propagation, vegetative multiplication or cloning) is any form of asexual reproduction occurring in plants in which a new plant grows from a fragment or cutting of the parent plant or spec ...
and are thus potentially immortal, while annual plants
An annual plant is a plant that completes its life cycle, from germination to the production of seeds, within one growing season, and then dies. The length of growing seasons and period in which they take place vary according to geographical ...
such as wheat and watermelons die each year and reproduce by sexual reproduction. In 2008 it was discovered that inactivation of only two genes in the annual plant ''Arabidopsis thaliana'' leads to its conversion into a potentially immortal perennial plant. The oldest animals known so far are 15,000-year-old Antarctic sponge
Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through t ...
s, which can reproduce both sexually and clonally.
Clonal immortality apart, there are certain species whose individual lifespans stand out among Earth's life-forms, including the bristlecone pine
The term bristlecone pine covers three species of pine tree (family Pinaceae, genus ''Pinus
A pine is any conifer tree or shrub in the genus ''Pinus'' () of the family Pinaceae. ''Pinus'' is the sole genus in the subfamily Pinoideae. T ...
at 5062 years or 5067 years,[ invertebrates like the ]hard clam
The hard clam ('' Mercenaria mercenaria''), also known as the round clam, hard-shell (or hard-shelled) clam, or the quahog, is an edible marine bivalve mollusk that is native to the eastern shores of North America and Central America from Prin ...
(known as ''quahog'' in New England) at 508 years, the Greenland shark
The Greenland shark (''Somniosus microcephalus''), also known as the gurry shark, grey shark, or by the Kalaallisut name ''eqalussuaq'', is a large shark of the family Somniosidae ("sleeper sharks"), closely related to the Pacific and souther ...
at 400 years, various deep-sea tube worms
A tubeworm is any worm-like sessility (zoology), sessile invertebrate that anchors its tail to an underwater surface and secretes around its body a mineral tube, into which it can withdraw its entire body.
Tubeworms are found among the following t ...
at over 300 years, fish like the sturgeon
Sturgeon is the common name for the 27 species of fish belonging to the family Acipenseridae. The earliest sturgeon fossils date to the Late Cretaceous
The Late Cretaceous (100.5–66 Ma) is the younger of two epochs into which the Cretace ...
and the rockfish
Rockfish is a common term for several species of fish, referring to their tendency to hide among rocks.
The name rockfish is used for many kinds of fish used for food. This common name belongs to several groups that are not closely related, and ca ...
, and the sea anemone
Sea anemones are a group of predation, predatory marine invertebrates of the order (biology), order Actiniaria. Because of their colourful appearance, they are named after the ''Anemone'', a terrestrial flowering plant. Sea anemones are classifi ...
and lobster
Lobsters are a family (biology), family (Nephropidae, Synonym (taxonomy), synonym Homaridae) of marine crustaceans. They have long bodies with muscular tails and live in crevices or burrows on the sea floor. Three of their five pairs of legs ...
. Such organisms are sometimes said to exhibit negligible senescence
Negligible senescence is a term coined by biogerontologist Caleb Finch to denote organisms that do not exhibit evidence of biological aging (senescence), such as measurable reductions in their reproductive capability, measurable functional decline ...
. The genetic aspect has also been demonstrated in studies of human centenarians
A centenarian is a person who has reached the age of 100 years. Because life expectancies worldwide are below 100 years, the term is invariably associated with longevity. In 2012, the United Nations estimated that there were 316,600 living centen ...
.
In laboratory settings, researchers have demonstrated that selected alterations in specific gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s can extend lifespan quite substantially in yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
and roundworms
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a broa ...
, less so in fruit flies
Fruit fly may refer to:
Organisms
* Drosophilidae, a family of small flies, including:
** ''Drosophila'', the genus of small fruit flies and vinegar flies
** ''Drosophila melanogaster'' or common fruit fly
** '' Drosophila suzukii'' or Asian frui ...
and less again in mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
. Some of the targeted genes have homologues across species and in some cases have been associated with human longevity. Studies by Becca Levy, an associate professor of epidemiology and psychology at the Yale School of Public Health
The Yale School of Public Health (YSPH) was founded in 1915 by Charles-Edward Amory Winslow and is one of the oldest public health masters programs in the United States. It is consistently rated among the best schools of public health in the co ...
, have found that positive beliefs about ageing may also increase life span.
* DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
: The strong effect of age on DNA methylation levels has been known since the late 1960s. Geneticist Steve Horvath hypothesised that DNA methylation age measures the cumulative effect of an epigenetic maintenance system but details are unknown. DNA methylation age of blood predicts all-cause mortality in later life. The epigenetic clock theory of ageing recognizes ageing as a by-product or unintended consequence of developmental and maintenance processes. Furthermore, prematurely aged mice can be rejuvenated and their lives extended by 30% by partially "resetting" the methylation pattern in their cells (a full reset leads to undesirable immortal cancer cells). This resetting into a juvenile state was experimentally achieved in 2016 by activating the four Yamanaka Yamanaka (written: ; lit: "middle of mountain") is a Japanese surname. Notable people with the surname include:
* Akira Joe Yamanaka, singer for the Flower Travellin' Band
* Akiko Yamanaka (born 1945), Japanese politician of the Liberal Democratic ...
DNA transcription factors – Sox2, Oct4
Oct-4 (octamer-binding transcription factor 4), also known as POU5F1 (POU domain, class 5, transcription factor 1), is a protein that in humans is encoded by the ''POU5F1'' gene. Oct-4 is a homeodomain transcription factor of the POU family. I ...
, Klf4 and c-Myc
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' ( MYC), ''l-myc'' ( MYCL), and ''n-myc'' ( MYCN). ''c-myc'' (also sometimes re ...
(which have previously been routinely used for producing young animals from cloned adult skin cells).
* Senescent cells: most of the cells with DNA damages that can't be fixed do apoptosis but some cells don't. Those cells are related to many diseases such as kidney failure and diabetes. In 2016, in a study, the removal of those cells in mice has extended their lifespans by 20% to 30%. Another study shows that this issue is related to the p16INK4a and β-galactosidase
β-Galactosidase (EC 3.2.1.23, lactase, beta-gal or β-gal; systematic name β-D-galactoside galactohydrolase), is a glycoside hydrolase enzyme that catalyzes hydrolysis of terminal non-reducing β-D-galactose residues in β-D-galactosides.
β ...
. Significant results have been obtained by some companies to extend mouse lifespan focusing on senescent cells.
* A variation in the gene FOXO3
Forkhead box O3, also known as FOXO3 or FOXO3a, is a human protein encoded by the ''FOXO3'' gene.
Function
FOXO3 belongs to the O subclass of the forkhead family of transcription factors which are characterized by a distinct fork head DNA-bi ...
A has a positive effect on the life expectancy of humans, and is found much more often in people living to 100 and beyond – moreover, this appears to be true worldwide. FOXO3A acts on the sirtuin
Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins t ...
family of genes which also have a significant effect on lifespan in yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
and in nematode
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...
s. Sirtuin in turn inhibits mTOR
The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MT ...
.
* Caloric restriction
Calorie restriction (caloric restriction or energy restriction) is a dietary regimen that reduces intake of energy from caloric foods & beverages without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake be ...
leads to longer lifespans in various species, an effect that is unclear, but probably mediated by the nutrient-sensing function of the mTOR pathway.
* mTOR
The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MT ...
, a protein that inhibits autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
, has been linked to ageing through the insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
signalling pathway. mTOR functions through nutrient and growth cues leading scientists to believe that dietary restriction and mTOR are related in terms of longevity. When organisms restrict their diet, mTOR activity is reduced, which allows an increased level of autophagy. This recycles old or damaged cell parts, which increases longevity and decreases the chances of being obese. This is thought to prevent spikes of glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
concentration in the blood, leading to reduced insulin signalling. This has been linked to less mTOR activation as well. Therefore, longevity has been connected to caloric restriction and insulin sensitivity inhibiting mTOR, which in turns allows autophagy to occur more frequently. It may be that mTOR inhibition and autophagy reduce the effects of reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
on the body, which damage DNA and other organic material, so longevity would be increased. In support of this contention are observations that several purported anti-ageing remedies such as rapamycin, metformin, berberine, 2-deoxyglucose, vitamin D3, aspirin and resveratrol were shown to suppress mTOR signaling and concurrently to reduce constitutive level of oxidative DNA damage induced by endogenous oxidants as well as to enhance the rate of autophagy
* A decreased Growth hormone/Insulin-like Growth Factor 1 signalling pathway has been associated with increased life span in various organisms including fruit flies, nematodes and mice. The precise mechanism by which decreased GH/IGF-1 signalling increases longevity is unknown, but various mouse strains with decreased GH and/or IGF-1 induced signalling share a similar phenotype which includes increased insulin sensitivity, enhanced stress resistance and protection from carcinogenesis. The studied mouse strains with decreased GH signalling showed between 20% and 68% increased longevity, and mouse strains with decreased IGF-1 induced signalling revealed a 19 to 33% increase in life span when compared to control mice.
* Over-expression of the Ras2 Ras2 is a ''Saccharomyces cerevisiae'' guanine nucleotide-binding protein (encoded by the RAS2 gene) which becomes activated by binding GTP when glucose is present in the environment. It affects growth regulation and starvation response.
Modifica ...
gene increases lifespan in yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
by 30%. A yeast mutant lacking the genes SCH9 and RAS1 has recently been shown to have a tenfold increase in lifespan under conditions of calorie restriction and is the largest increase achieved in any organism.
* Telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
s: In humans and other animals, cellular senescence
Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence inv ...
has been attributed to the shortening of telomeres at each cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
; when telomeres become too short, the cells senesce and die or cease multiplying. The length of telomeres is therefore the "molecular clock", predicted by Hayflick.[Bernstein C, Bernstein H. (1991) ''Aging, Sex, and DNA Repair''. Academic Press, San Diego. . pp. 314, 320, 326] However, telomere length in wild mouse strains is unrelated to lifespan, and mice lacking the enzyme telomerase do not have a dramatically reduced lifespan. Laboratory mice's telomeres are many times longer than human ones. Another caveat is that a study following nearly 1000 humans for ten years showed that while some humans do shorten their telomeres over time, a third of the participants did not.
** The theory would explain why the autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
disease, Huntington's disease
Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
, can persist even though it is inexorably lethal. Also, it has been suggested that some of the genetic variants that increase fertility in the young increase cancer risk in the old. Such variants occur in genes p53 and BRCA1.
** The reproductive-cell cycle theory argues that ageing is regulated specifically by reproductive hormones that act in an antagonistic pleiotropic
Pleiotropy (from Greek , 'more', and , 'way') occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic ge ...
manner via cell cycle signalling, promoting growth and development early in life to achieve reproduction, but becoming dysregulated later in life, driving senescence (dyosis) in a futile attempt to maintain reproductive ability. The endocrine dyscrasia that follows the loss of follicles with menopause, and the loss of Leydig and Sertoli cells during andropause, drive aberrant cell cycle signalling that leads to cell death and dysfunction, tissue dysfunction (disease) and ultimately death. Moreover, the hormones that regulate reproduction also regulate cellular metabolism, explaining the increases in fat deposition during pregnancy through to the deposition of centralised adiposity with the dysregulation of the HPG axis following menopause and during andropause (Atwood and Bowen, 2004). This theory, which introduced a new definition of ageing, has facilitated the conceptualisation of why and how ageing occurs at the evolutionary, physiological and molecular levels.
* Autoimmunity: The idea that ageing results from an increase in autoantibodies that attack the body's tissues. A number of diseases associated with ageing, such as atrophic gastritis
Atrophic gastritis is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion o ...
and Hashimoto's thyroiditis
Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...
, are probably autoimmune in this way. However, while inflammation is very much evident in old mammals, even completely immunodeficient
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
mice raised in pathogen-free laboratory conditions still experience senescence.
* The cellular balance between energy generation and consumption (energy homeostasis) requires tight regulation during ageing. In 2011, it was demonstrated that acetylation levels of AMP-activated protein kinase
5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cell ...
change with age in yeast and that preventing this change slows yeast ageing.
* Skin ageing is caused in part by TGF-β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
, which reduces the subcutaneous fat that gives skin a pleasant appearance and texture. TGF-β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
does this by blocking the conversion of dermal fibroblasts into fat cells
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...
; with fewer fat cells underneath to provide support, the skin becomes saggy and wrinkled. Subcutaneous fat also produces cathelicidin
Cathelicidin antimicrobial peptide (CAMP) is a polypeptide that is primarily stored in the lysosomes of macrophages and polymorphonuclear leukocytes (PMNs); in humans, the ''CAMP'' gene encodes the peptide precursor CAP-18 (18 kDa), which is proce ...
, which is a peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
that fights bacterial infections.
Evolution of ageing
Life span, like other phenotypes
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
, is selected for in evolution. Traits that benefit early survival and reproduction will be selected for even if they contribute to an earlier death. Such a genetic effect is called the antagonistic pleiotropy effect when referring to a gene (pleiotropy signifying the gene has a double function – enabling reproduction at a young age but costing the organism life expectancy in old age) and is called the disposable soma
The disposable soma theory of aging states that organisms age due to an evolutionary trade-off between growth, reproduction, and DNA repair maintenance. Formulated by Thomas Kirkwood, the disposable soma theory explains that an organism only has ...
effect when referring to an entire genetic programme (the organism diverting limited resources from maintenance to reproduction). The biological mechanisms which regulate lifespan probably evolved with the first multicellular organisms more than a billion years ago. However, even single-celled organisms such as yeast have been used as models in ageing, hence ageing has its biological roots much earlier than multi-cellularity.
Damage-related factors
* DNA damage theory of ageing: DNA damage is thought to be the common basis of both cancer and ageing, and it has been argued that intrinsic causes of DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
are the most important drivers of ageing. Genetic damage (aberrant structural alterations of the DNA), mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s (changes in the DNA sequence), and epimutations ( methylation of gene promoter regions or alterations of the DNA scaffolding which regulate gene expression), can cause abnormal gene expression. DNA damage causes the cells to stop dividing or induces apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
, often affecting stem cell pools and hence hindering regeneration. However, lifelong studies of mice suggest that most mutations happen during embryonic and childhood development, when cells divide often, as each cell division is a chance for errors in DNA replication.
* Genetic instability
Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneu ...
: Dogs annually lose approximately 3.3% of the DNA in their heart muscle cells while humans lose approximately 0.6% of their heart muscle DNA each year. These numbers are close to the ratio of the maximum longevities of the two species (120 years vs. 20 years, a 6/1 ratio). The comparative percentage is also similar between the dog and human for yearly DNA loss in the brain and lymphocytes. As stated by lead author, Bernard L. Strehler
Bernard Strehler (1925–2001) was an early biogerontologist. He published the book ''Time, Cells, and Aging''.
In 1949, he helped discover the firefly luciferin 2, which gives off light after being combined with ATP. In 1956, he switched to the ...
, "... genetic damage (particularly gene loss) is almost certainly (or probably the) central cause of ageing."
* Accumulation of waste:
** A buildup of waste products in cells presumably interferes with metabolism. For example, a waste product called lipofuscin
Lipofuscin is the name given to fine yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered to be one of the aging or "wear-and-tear" pigments, found in the liver, kidney, heart muscle, reti ...
is formed by a complex reaction in cells that binds fat to proteins. This waste accumulates in the cells as small granules, which increase in size as a person ages.
** The hallmark of ageing yeast cells appears to be overproduction of certain proteins.
** Autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Autophagy is enhanced in obese mice by caloric restriction, exercise, and a low fat diet (but in these mice is evidently not related with the activation of AMP-activated protein kinase
5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cell ...
, see above).
* Wear-and-tear theory: The very general idea that changes associated with ageing are the result of chance damage that accumulates over time.
* Accumulation of errors: The idea that ageing results from chance events that escape proof reading mechanisms, which gradually damages the genetic code.
* Heterochromatin loss, model of ageing.
* Transposable elements
A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Trans ...
in genome disintegration as the primary role in the mechanism of ageing.
* Cross-linkage: The idea that ageing results from accumulation of cross-linked
In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...
compounds that interfere with normal cell function.
* Studies of mtDNA mutator mice have shown that increased levels of somatic mtDNA mutations directly can cause a variety of ageing phenotypes. The authors propose that mtDNA mutations lead to respiratory-chain-deficient cells and thence to apoptosis and cell loss. They cast doubt experimentally however on the common assumption that mitochondrial mutations and dysfunction lead to increased generation of reactive oxygen species (ROS).
* Free-radical theory
In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron.
With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spo ...
: Damage by free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
s, or more generally reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
or oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
, create damage that may give rise to the symptoms we recognise as ageing. Michael Ristow's group has provided evidence that the effect of calorie restriction may be due to increased formation of free radicals
In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron.
With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spont ...
within the mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
, causing a secondary induction of increased antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
defence capacity.
*Mitochondrial theory of ageing
The mitochondrial theory of ageing has two varieties: free radical and non-free radical. The first is one of the variants of the free radical theory of ageing. It was formulated by J. Miquel and colleagues in 1980 and was developed in the works of ...
: free radicals
In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron.
With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spont ...
produced by mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
l activity damage cellular components, leading to ageing.
* DNA oxidation
DNA oxidation is the process of oxidative damage of deoxyribonucleic acid. As described in detail by Burrows et al., 8-oxo-2'-deoxyguanosine (8-oxo-dG) is the most common oxidative lesion observed in duplex DNA because guanine has a lower one-el ...
and caloric restriction: Caloric restriction reduces 8-OH-dG DNA damage in organs of ageing rats and mice. Thus, reduction of oxidative DNA damage is associated with a slower rate of ageing and increased lifespan. In a 2021 review article, Vijg stated that "Based on an abundance of evidence, DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
is now considered as the single most important driver of the degenerative processes that collectively cause aging."
Prevention and delay
Lifestyle
Caloric restriction
Calorie restriction (caloric restriction or energy restriction) is a dietary regimen that reduces intake of energy from caloric foods & beverages without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake be ...
substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases. Typically, this involves caloric intake of 60–70% of what an ''ad libitum
In music and other performing arts, the phrase (; from Latin for 'at one's pleasure' or 'as you desire'), often shortened to "ad lib" (as an adjective or adverb) or "ad-lib" (as a verb or noun), refers to various forms of improvisation.
The ...
'' animal would consume, while still maintaining proper nutrient intake. In rodents, this has been shown to increase lifespan by up to 50%; similar effects occur for yeast and ''Drosophila''. No lifespan data exist for humans on a calorie-restricted diet, but several reports support protection from age-related diseases. Two major ongoing studies on rhesus monkeys
The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies that are split between two groups, the Chinese-derived and the Indian-derived. Generally b ...
initially revealed disparate results; while one study, by the University of Wisconsin, showed that caloric restriction does extend lifespan, the second study, by the National Institute on Aging (NIA), found no effects of caloric restriction on longevity. Both studies nevertheless showed improvement in a number of health parameters. Notwithstanding the similarly low calorie intake, the diet composition differed between the two studies (notably a high sucrose
Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula .
For human consumption, sucrose is extracted and refined ...
content in the Wisconsin study), and the monkeys have different origins (India, China), initially suggesting that genetics and dietary composition, not merely a decrease in calories, are factors in longevity. However, in a comparative analysis in 2014, the Wisconsin researchers found that the allegedly non-starved NIA control monkeys in fact are moderately underweight when compared with other monkey populations, and argued this was due to the NIA's apportioned feeding protocol in contrast to Wisconsin's truly unrestricted ''ad libitum'' feeding protocol. They conclude that moderate calorie restriction rather than extreme calorie restriction is sufficient to produce the observed health and longevity benefits in the studied rhesus monkeys.
In his book ''How and Why We Age'', Hayflick says that caloric restriction may not be effective in humans, citing data from the Baltimore Longitudinal Study of Aging which shows that being thin does not favour longevity. However, there may be confounders, e.g. smoking reduces both appetite and lifespan. Similarly, it is sometimes claimed that moderate ''obesity'' in later life may improve survival, but newer research has identified confounding factors such as weight loss due to terminal disease. Once these factors are accounted for, the optimal body weight above age 65 corresponds to a leaner body mass index
Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...
of 23 to 27.
Alternatively, the benefits of dietary restriction can also be found by changing the macro nutrient profile to reduce protein intake without any changes to calorie level, resulting in similar increases in longevity. Dietary protein restriction not only inhibits mTOR activity but also IGF-1, two mechanisms implicated in ageing. Specifically, reducing leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...
intake is sufficient to inhibit mTOR activity, achievable through reducing animal food consumption.
The Mediterranean diet
The Mediterranean diet is a diet inspired by the eating habits of people who live near the Mediterranean Sea. When initially formulated in the 1960s, it drew on the cuisines of Greece, Italy, France and Spain. In decades since, it has also incor ...
is credited with lowering the risk of heart disease and early death. The major contributors to mortality risk reduction appear to be a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids, i.e., olive oil.
On the other hand, the consumption of certain foods such as sugar, refined carbohydrates, alcohol, processed meats and fried food, accelerates ageing.
The amount of sleep
Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a de ...
has an impact on mortality. People who live the longest report sleeping for six to seven hours each night. Lack of sleep (<5 hours) more than doubles the risk of death from cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
, but too much sleep (>9 hours) is associated with a doubling of the risk of death, though not primarily from cardiovascular disease. Sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality, though the cause is probably other factors such as depression and socioeconomic status, which would correlate statistically. Sleep monitoring of hunter-gatherer tribes from Africa and from South America has shown similar sleep patterns across continents: their average sleeping duration is 6.4 hours (with a summer/winter difference of 1 hour), afternoon naps (siesta
A ''siesta'' (from Spanish, pronounced and meaning "nap") is a short nap taken in the early afternoon, often after the midday meal. Such a period of sleep is a common tradition in some countries, particularly those in warm-weather zones. Th ...
s) are uncommon, and insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
is very rare (tenfold less than in industrial societies).
Physical exercise
Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness.
It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic ...
may increase life expectancy. People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active. Moderate levels of exercise have been correlated with preventing ageing and improving quality of life by reducing inflammatory potential. The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent
The metabolic equivalent of task (MET) is the objective measure of the ratio of the rate at which a person expends energy, relative to the mass of that person, while performing some specific physical activity compared to a reference, set by convent ...
(MET) minutes per week.[ For example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or bicycling for 25 minutes on a daily basis would ''together'' achieve about 3000 MET minutes a week.] Other research seems to suggest a relationship between regular physical exercise and cognitive functioning in old age.
Avoidance of chronic stress
Chronic stress is the physiological or psychological response induced by a long-term internal or external stressor. The stressor, either physically present or recollected, will produce the same effect and trigger a chronic stress response. There i ...
(as opposed to acute stress) is associated with a slower loss of telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
s in most but not all studies, and with decreased cortisol levels. A chronically high cortisol level compromises the immune system, causes cardiac damage/ arterosclerosis and is associated with facial ageing, and the latter in turn is a marker for increased morbidity and mortality. A meta-analysis shows that loneliness carries a higher mortality risk than smoking. Stress can be countered by social connection, spirituality, and (for men more clearly than for women) married life, all of which are associated with longevity.
Medical intervention
The following drugs and interventions have been shown to slow or reverse the biological effects of ageing in animal models, but none has yet been proven to do so in humans. In a critical review, Wolf (2021) points out that these commonly promulgated anti-ageing compounds (resveratrol, rapamycin, nicotinamide mononucleotide and metformin) all cause weight loss, a feature that is "downplayed" in many anti-ageing publications; it is therefore likely that the compounds only counteract the life-shortening effects of obesity, and would not benefit individuals who have normal body weight.
Scientists have begun to explore calorie-restriction mimetics-natural and synthetic drug compounds that might yield the same health effects as calorie restriction, without dieting. These investigations are still in their early stages. Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.
, metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
was under study for its potential effect on slowing ageing in the worm ''C.elegans'' and the cricket
Cricket is a bat-and-ball game played between two teams of eleven players on a field at the centre of which is a pitch with a wicket at each end, each comprising two bails balanced on three stumps. The batting side scores runs by striki ...
.[ Its effect on otherwise healthy humans is unknown.] In 2019, Fahy and colleagues reported that a two-year trial on nine humans using metformin to regenerate thymus tissue unexpectedly resulted in a reversal of ageing as measured by DNA methylation levels.
Rapamycin
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosi ...
was first shown to extend lifespan in eukaryotes in 2006 by Powers ''et al.'' who showed a dose-responsive effect of rapamycin on lifespan extension in yeast cells. In a 2009 study, the lifespans of mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
fed rapamycin were increased between 28 and 38% from the beginning of treatment, or 9 to 14% in total increased maximum lifespan. Of particular note, the treatment began in mice aged 20 months, the equivalent of 60 human years.[
*] Rapamycin has subsequently been shown to extend mouse lifespan in several separate experiments, and is now being tested for this purpose in nonhuman primates (the marmoset
The marmosets (), also known as zaris or sagoin, are 22 New World monkey species of the genera '' Callithrix'', '' Cebuella'', '' Callibella'', and ''Mico''. All four genera are part of the biological family Callitrichidae. The term "marmoset" ...
monkey).
Cancer geneticist Ronald A. DePinho
Ronald A. DePinho (born 1955) is an American physician and research scientist. He served as president of MD Anderson Cancer Center from 2011 to 2017. DePinho states that his concern for reducing the burden of cancer suffering became his life goal ...
and his colleagues published research on mice where telomerase
Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most euka ...
activity was first genetically removed. Then, after the mice had prematurely aged, they restored telomerase activity by reactivating the telomerase gene. As a result, the mice were rejuvenated: Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver, intestines and brain, recuperated from their degenerated state. " he findingoffers the possibility that normal human ageing could be slowed by reawakening the enzyme in cells where it has stopped working" says Ronald DePinho. However, activating telomerase in humans could potentially encourage the growth of tumours.
Most known genetic interventions in ''C. elegans'' increase lifespan by 1.5 to 2.5-fold. , the record for lifespan extension in C. ''elegans'' is a single-gene mutation which increases adult survival by tenfold. The strong conservation of some of the mechanisms of ageing discovered in model organisms imply that they may be useful in the enhancement of human survival. However, the benefits may not be proportional; longevity gains are typically greater in ''C. elegans'' than fruit flies, and greater in fruit flies than in mammals. One explanation for this is that mammals, being much longer-lived, already have many traits which promote lifespan.
Mitochondria-targeted antioxidant SkQ1 has been shown to extend the lifespan of mice.
Research projects and prizes
Some research effort is directed to slow ageing and extend healthy lifespan.
In 1993, the Established populations for epidemiologic studies of the elderly, also known as the Yale Health and Aging Study, showed the importance of physical activity and argued against negative stereotypes concerning old age.
Dr. David Snowdon's Nun Study on aging and Alzheimer's disease has many interesting discoveries about memory, the impact of positively expressed emotions and how to live a longer, higher quality life.
A paper published on 29 March 2022 by a group of scientists at Insilico Medicine, University of Chicago
The University of Chicago (UChicago, Chicago, U of C, or UChi) is a private research university in Chicago, Illinois. Its main campus is located in Chicago's Hyde Park neighborhood. The University of Chicago is consistently ranked among the b ...
, George Mason University
George Mason University (George Mason, Mason, or GMU) is a public research university in Fairfax County, Virginia with an independent City of Fairfax, Virginia postal address in the Washington, D.C. Metropolitan Area. The university was origin ...
, and University of Liverpool
, mottoeng = These days of peace foster learning
, established = 1881 – University College Liverpool1884 – affiliated to the federal Victoria Universityhttp://www.legislation.gov.uk/ukla/2004/4 University of Manchester Act 200 ...
demonstrated that there might be several alternative senolytic targets and pathways that can be targeted with small molecules drugs. They use artificial intelligence
Artificial intelligence (AI) is intelligence—perceiving, synthesizing, and inferring information—demonstrated by machines, as opposed to intelligence displayed by animals and humans. Example tasks in which this is done include speech re ...
models to yield a list of dual-purpose targets implicated in ageing and age-associated diseases. It may impact multiple age-associated diseases and retard ageing for extending healthspan.
The US National Institute on Aging
The National Institute on Aging (NIA) is a division of the U.S. National Institutes of Health (NIH), located in Bethesda, Maryland. The NIA itself is headquartered in Baltimore, Maryland.
The NIA leads a broad scientific effort to understand the ...
currently funds an intervention testing programme, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice. Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals and lax mouse husbandry conditions. The intervention testing programme aims to address this by conducting parallel experiments at three internationally recognised mouse ageing-centres, the Barshop Institute at UTHSCSA
The University of Texas Health Science Center at San Antonio (UT Health San Antonio) is a public academic health science center in San Antonio, Texas. It is part of the University of Texas System.
UT Health San Antonio is the largest health scie ...
, the University of Michigan
, mottoeng = "Arts, Knowledge, Truth"
, former_names = Catholepistemiad, or University of Michigania (1817–1821)
, budget = $10.3 billion (2021)
, endowment = $17 billion (2021)As o ...
at Ann Arbor and the Jackson Laboratory.
Several companies and organisations, such as Google Calico
Calico Life Sciences LLC is an Alphabet subsidiary responsible for health research and development, life sciences and biotechnology. Originating on September 18, 2013 prior to the Google restructuring and headed by Bill Maris with the goal ...
, Human Longevity
Human Longevity, Inc. is a San Diego-based venture launched by Craig Venter and Peter Diamandis in 2013. Its goal is to build the world's most comprehensive database on human genotypes and phenotypes, and then subject it to machine learning so tha ...
, Craig Venter
John Craig Venter (born October 14, 1946) is an American biotechnologist and businessman. He is known for leading one of the first draft sequences of the human genome and assembled the first team to transfect a cell with a synthetic chromosome. ...
, Gero, SENS Research Foundation
The SENS Research Foundation is a non-profit organization that does research programs and public relations work for the application of regenerative medicine to aging. It was founded in 2009, located in Mountain View, California, USA. The organiza ...
, and Science for Life Extension in Russia, declared stopping or delaying ageing as their goal.
Prizes for extending lifespan and slowing ageing in mammals exist. The Methuselah Foundation
The Methuselah Foundation is an American-based global non-profit organization, based in Springfield, Virginia, with a declared mission to "make 90 the new 50 by 2030" by supporting tissue engineering and regenerative medicine therapies. The orga ...
offers the Mprize. Recently, the $1 Million Palo Alto Longevity Prize was launched. It is a research incentive prize to encourage teams from all over the world to compete in an all-out effort to "hack the code" that regulates our health and lifespan. It was founded by Joon Yun
Anthony Joonkyoo "Joon" Yun (born 1967) is a Koreans, Korean-Americans, American physician, hedge fund, hedge-fund manager and investor.
Early life, education and early career
Yun was born in Seoul, South Korea. He attended St. Albans School ( ...
.
Society and culture
Different cultures express age in different ways. The age of an adult human is commonly measured in whole years since the day of birth. Arbitrary divisions set to mark periods of life may include: juvenile (via infancy, childhood
A child (plural, : children) is a human being between the stages of childbirth, birth and puberty, or between the Development of the human body, developmental period of infancy and puberty. The legal definition of ''child'' generally refers ...
, preadolescence
Preadolescence is a stage of human development following middle childhood and preceding adolescence.New Oxford American Dictionary. 2nd Edition. 2005. Oxford University Press. It commonly ends with the beginning of puberty. Preadolescence is ...
, adolescence
Adolescence () is a transitional stage of physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with the t ...
), early adulthood
Emerging adulthood refers to a phase of the life span between late adolescence and early adulthood, as initially proposed by Jeffrey Arnett in a 2000 article from the ''American Psychologist''. It primarily describes people living in developed co ...
, middle adulthood, and late adulthood. More casual terms may include "teenagers", " tweens", "twentysomething", "thirtysomething", etc. as well as "denarian", "vicenarian", "tricenarian", "quadragenarian", etc.
Most legal systems define a specific age for when an individual is allowed or obliged to do particular activities. These age specifications include voting age
A voting age is a minimum age established by law that a person must attain before they become eligible to vote in a public election. The most common voting age is 18 years; however, voting ages as low as 16 and as high as 25 currently exist
( ...
, drinking age
The legal drinking age is the minimum age at which a person can legally consume alcoholic beverages. The minimum age alcohol can be legally consumed can be different from the age when it can be purchased in some countries. These laws vary between ...
, age of consent, age of majority
The age of majority is the threshold of legal adulthood as recognized or declared in law. It is the moment when minors cease to be considered such and assume legal control over their persons, actions, and decisions, thus terminating the contr ...
, age of criminal responsibility, marriageable age, age of candidacy
Age of candidacy is the minimum age at which a person can legally hold certain elected government offices. In many cases, it also determines the age at which a person may be eligible to stand for an election or be granted ballot access.
The firs ...
, and mandatory retirement age
Mandatory retirement also known as forced retirement, enforced retirement or compulsory retirement, is the set age at which people who hold certain jobs or offices are required by industry custom or by law to leave their employment, or retire.
As ...
. Admission to a movie for instance, may depend on age according to a motion picture rating system
A motion picture content rating system classifies films based on their suitability for audiences due to their treatment of issues such as sex, violence, or substance abuse; their use of profanity; or other matters typically deemed unsuitable for c ...
. A bus fare might be discounted for the young or old. Each nation, government and non-governmental organisation has different ways of classifying age. In other words, chronological
Chronology (from Latin ''chronologia'', from Ancient Greek , ''chrónos'', "time"; and , '' -logia'') is the science of arranging events in their order of occurrence in time. Consider, for example, the use of a timeline or sequence of events. ...
ageing may be distinguished from "social ageing" (cultural age-expectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as it ages).
Ageism cost the United States $63 billion in one year according to a Yale School of Public Health
The Yale School of Public Health (YSPH) was founded in 1915 by Charles-Edward Amory Winslow and is one of the oldest public health masters programs in the United States. It is consistently rated among the best schools of public health in the co ...
study. In a UNFPA report about ageing in the 21st century, it highlighted the need to "Develop a new rights-based culture of ageing and a change of mindset and societal attitudes towards ageing and older persons, from welfare recipients to active, contributing members of society". UNFPA said that this "requires, among others, working towards the development of international human rights instruments and their translation into national laws and regulations and affirmative measures that challenge age discrimination and recognise older people as autonomous subjects". Older people's music participation contributes to the maintenance of interpersonal relationships and promoting successful ageing. At the same time, older persons can make contributions to society including caregiving and volunteering. For example, "A study of Bolivian migrants who admoved to Spain found that 69% left their children at home, usually with grandparents. In rural China, grandparents care for 38% of children aged under five whose parents have gone to work in cities."
Economics
Population ageing is the increase in the number and proportion of older people in society. Population ageing has three possible causes: migration, longer life expectancy
Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
(decreased death rate) and decreased birth rate. Ageing has a significant impact on society. Young people tend to have fewer legal privileges (if they are below the age of majority
The age of majority is the threshold of legal adulthood as recognized or declared in law. It is the moment when minors cease to be considered such and assume legal control over their persons, actions, and decisions, thus terminating the contr ...
), they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. Older people have different requirements from society and government, and frequently have differing values as well, such as for property and pension rights.
In the 21st century, one of the most significant population trends is ageing. Currently, over 11% of the world's current population are people aged 60 and older and the United Nations Population Fund
The United Nations Population Fund (UNFPA), formerly the United Nations Fund for Population Activities, is a UN agency aimed at improving reproductive and maternal health worldwide. Its work includes developing national healthcare strategies ...
(UNFPA) estimates that by 2050 that number will rise to approximately 22%. Ageing has occurred due to development which has enabled better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy has risen. Life expectancy at birth is over 80 now in 33 countries. Ageing is a "global phenomenon", that is occurring fastest in developing countries, including those with large youth populations, and poses social and economic challenges to the work which can be overcome with "the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits".
As life expectancy rises and birth rates
The birth rate for a given period is the total number of live human births per 1,000 population divided by the length of the period in years. The number of live births is normally taken from a universal registration system for births; populati ...
decline in developed countries, the median
In statistics and probability theory, the median is the value separating the higher half from the lower half of a data sample, a population, or a probability distribution. For a data set, it may be thought of as "the middle" value. The basic fe ...
age rises accordingly. According to the United Nations
The United Nations (UN) is an intergovernmental organization whose stated purposes are to maintain international peace and international security, security, develop friendly relations among nations, achieve international cooperation, and be ...
, this process is taking place in nearly every country in the world. A rising median age can have significant social and economic implications, as the workforce gets progressively older and the number of old workers and retirees grows relative to the number of young workers. Older people generally incur more health-related costs than do younger people in the workplace and can also cost more in worker's compensation and pension liabilities. In most developed countries an older workforce is somewhat inevitable. In the United States for instance, the Bureau of Labor Statistics
The Bureau of Labor Statistics (BLS) is a unit of the United States Department of Labor. It is the principal fact-finding agency for the U.S. government in the broad field of labor economics and statistics and serves as a principal agency of t ...
estimates that one in four American workers will be 55 or older by 2020.[
Among the most urgent concerns of older persons worldwide is income security. This poses challenges for governments with ageing populations to ensure investments in pension systems continues in order to provide economic independence and reduce poverty in old age. These challenges vary for developing and developed countries. UNFPA stated that, "Sustainability of these systems is of particular concern, particularly in developed countries, while social protection and old-age pension coverage remain a challenge for developing countries, where a large proportion of the labour force is found in the informal sector."]
The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age. In order to elevate this pressure "social protection floors must be implemented in order to guarantee income security and access to essential health and social services for all older persons and provide a safety net that contributes to the postponement of disability and prevention of impoverishment in old age".
It has been argued that population ageing has undermined economic development and can lead to lower inflation because elderly individuals care especially strongly about the value of their pensions and savings Evidence suggests that pensions, while making a difference to the well-being of older persons, also benefit entire families especially in times of crisis when there may be a shortage or loss of employment within households. A study by the Australian Government in 2003 estimated that "women between the ages of 65 and 74 years contribute A$16 billion per year in unpaid caregiving and voluntary work. Similarly, men in the same age group contributed A$10 billion per year."
Due to increasing share of the elderly in the population, health care expenditures will continue to grow relative to the economy in coming decades. This has been considered as a negative phenomenon and effective strategies like labour productivity enhancement should be considered to deal with negative consequences of ageing.
Sociology
In the field of sociology and mental health, ageing is seen in five different views: ageing as maturity, ageing as decline, ageing as a life-cycle event, ageing as generation, and ageing as survival. Positive correlates with ageing often include economics, employment, marriage, children, education, and sense of control, as well as many others. The social science of ageing includes disengagement theory, activity theory, selectivity theory, and continuity theory. Retirement
Retirement is the withdrawal from one's position or occupation or from one's active working life. A person may also semi-retire by reducing work hours or workload.
Many people choose to retire when they are elderly or incapable of doing their j ...
, a common transition faced by the elderly, may have both positive and negative consequences. As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of ageing and for instance a bio-techno-social definition of ageing has been suggested.
There is a current debate as to whether or not the pursuit of longevity
The word " longevity" is sometimes used as a synonym for "life expectancy" in demography. However, the term ''longevity'' is sometimes meant to refer only to especially long-lived members of a population, whereas ''life expectancy'' is always d ...
and the postponement of senescence are cost-effective health care goals given finite health care resources. Because of the accumulated infirmities of old age, bioethicist Ezekiel Emanuel
Ezekiel Jonathan "Zeke" Emanuel (born September 6, 1957) is an American oncologist, bioethicist and senior fellow at the Center for American Progress. He is the current Vice Provost for Global Initiatives at the University of Pennsylvania and chai ...
, opines that the pursuit of longevity via the compression of morbidity hypothesis is a "fantasy" and that human life is not worth living after age 75; longevity then should not be a goal of health care policy. This opinion has been contested by neurosurgeon and medical ethicist Miguel Faria, who states that life can be worthwhile during old age, and that longevity should be pursued in association with the attainment of quality of life. Faria claims that postponement of senescence as well as happiness and wisdom can be attained in old age in a large proportion of those who lead healthy lifestyles and remain intellectually active.
Health care demand
With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that:
"A life-cycle approach to health care – one that starts early, continues through the reproductive years and lasts into old age – is essential for the physical and emotional well-being of older persons, and, indeed, all people. Public policies and programmes should additionally address the needs of older impoverished people who cannot afford health care."
Many societies in Western Europe and Japan have ageing populations. While the effects on society are complex, there is a concern about the impact on health care demand. The large number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in ageing societies can be organised under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.
However, the annual growth in national health spending is not mainly due to increasing demand from ageing populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients. A number of health problems become more prevalent as people get older. These include mental health problems as well as physical health problems, especially dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
.
It has been estimated that population ageing only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3% since 1970. In addition, certain reforms to the Medicare system in the United States decreased elderly spending on home health care by 12.5% per year between 1996 and 2000.
Self-perception
Beauty standards
Physical attractiveness is the degree to which a person's physical features are considered aesthetically pleasing or beautiful. The term often implies sexual attractiveness or desirability, but can also be distinct from either. There are many ...
have evolved over time, and as scientific research in cosmeceuticals has increased, the industry has also expanded; the kinds of products they produce (such as serums and creams) have gradually gained popularity and become a part of many people's personal care routine. The cosmeceutical industry is currently the fastest growing beauty industry, with a market size of $49.5 billion for the year 2018.
The increase in demand for cosmeceuticals has led scientists to find ingredients for these products in unorthodox places. For example, the secretion of cryptomphalus aspersa (or brown garden snail) has been found to have antioxidant properties, increase skin cell proliferation, as well as increase extracellular proteins such as collagen and fibronectin (important proteins for cell proliferation). Another substance used to prevent the physical manifestations of ageing is onobotulinumtoxinA, the toxin injected for Botox.
Generally, aversion to aging is a Western attitude. However, in other places around the world, old age is celebrated and honored. In Korea, for example, a special party called hwangap is held to celebrate and congratulate an individual for turning 60 years old. In China, respect for elderly is often the basis for how a community is organized and has been at the foundation of Chinese culture and morality for thousands of years. Older people are respected for their wisdom and most important decisions have traditionally not been made without consulting them. This is a similar case for most Asian countries such as the Philippines, Thailand, Vietnam, Singapore, etc.
Positive self-perceptions of ageing are associated with better mental and physical health and well-being. Positive self-perception of health has been correlated with higher well-being and reduced mortality among the elderly. Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better as than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status. This finding is generally stronger for men than women,[ though this relationship is not universal across all studies and may only be true in some circumstances.][
As people age, subjective health remains relatively stable, even though objective health worsens.] In fact, perceived health improves with age when objective health is controlled in the equation. This phenomenon is known as the "paradox of ageing". This may be a result of social comparison
Social comparison theory, initially proposed by social psychologist Leon Festinger in 1954, centers on the belief that there is a drive within individuals to gain accurate self-evaluations. The theory explains how individuals evaluate their own o ...
; for instance, the older people get, the more they may consider themselves in better health than their same-aged peers. Elderly people often associate their functional and physical decline with the normal ageing process.
One way to help younger people experience what it feels like to be older is through an ageing suit. There are several different kinds of suits including the GERT (named as a reference to gerontology), the R70i exoskeleton, and the AGNES (Age Gain Now Empathy Suit) suits. These suits create the feelings of the effects of ageing by adding extra weight and increased pressure in certain points like the wrists, ankles and other joints. In addition, the various suits have different ways to impair vision and hearing to simulate the loss of these senses. To create the loss of feeling in hands that the elderly experience, special gloves are a part of the uniforms.
Use of these suits may help to increase the amount of empathy felt for the elderly and could be considered particularly useful for those who are either learning about ageing, or those who work with the elderly, such as nurses or care center staff.
Empathy is another field that could benefit from the empathy these suits may cause. When designers understand what it feels like to have the impairments of old age, they can better design buildings, packaging, or even tools to help with the simple day-to-day tasks that are more difficult with less dexterity. Designing with the elderly in mind may help to reduce the negative feelings that are associated with the loss of abilities that the elderly face.
Successful ageing
The concept of ''successful ageing'' can be traced back to the 1950s and was popularized in the 1980s. Traditional definitions of successful ageing have emphasized absence of physical and cognitive disabilities. In their 1987 article, Rowe and Kahn characterized successful ageing as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement. The study cited previous was also done back in 1987 and therefore, these factors associated with successful aging have probably been changed. With the current knowledge, scientists started to focus on learning about the effect spirituality in successful aging. There are some differences in cultures which of these components are the most important. Most often across cultures social engagement was the most highly rated but depending on the culture the definition of successful ageing changes.
Cultural references
The ancient Greek dramatist Euripides
Euripides (; grc, Εὐριπίδης, Eurīpídēs, ; ) was a tragedian
Tragedy (from the grc-gre, τραγῳδία, ''tragōidia'', ''tragōidia'') is a genre of drama based on human suffering and, mainly, the terrible or sorrowful e ...
(5th century BC) describes the multiple-headed mythological monster Hydra as having a regenerative capacity which makes it immortal, which is the historical background to the name of the biological genus Hydra. The Book of Job
The Book of Job (; hbo, אִיּוֹב, ʾIyyōḇ), or simply Job, is a book found in the Ketuvim ("Writings") section of the Hebrew Bible (Tanakh), and is the first of the Poetic Books in the Old Testament of the Christian Bible. Scholars ar ...
(c. 6th century BC) describes human lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing vegetative regeneration.[Job 14:5–7 ''A man's days are numbered. You know the number of his months. He cannot live longer than the time You have set. So now look away from him that he may rest, until he has lived the time set for him like a man paid to work. For there is hope for a tree, when it is cut down, that it will grow again, and that its branches will not stop growing'']
See also
* Ageing brain
Aging is a major risk factor for most common neurodegenerative diseases, including mild cognitive impairment, dementias including Alzheimer's disease, cerebrovascular disease, Parkinson's disease, and Lou Gehrig's disease. While much research has ...
* Ageing movement control
* Ageing of Europe
The ageing of Europe, also known as the greying of Europe, is a demographic phenomenon in Europe characterised by a decrease in fertility, a decrease in mortality rate, and a higher life expectancy among European populations. Low birth rates an ...
* Ageing studies
Ageing studies (or age studies) is a field of theoretically, politically, and empirically engaged cultural analysis that was developed by scholars from many different disciplines. Over the past fifteen years the field of ageing studies has flouris ...
* Anti-ageing movement
The anti-aging movement is a social movement devoted to eliminating or reversing aging, or reducing the effects of it. A substantial portion of the attention of the movement is on the possibilities for life extension, but there is also interest ...
* Biodemography of human longevity
Biodemography is a multidisciplinary approach, integrating biological knowledge (studies on human biology and animal models) with demographic research on human longevity and survival. Biodemographic studies are important for understanding the driv ...
* Biogerontology
Biogerontology is the sub-field of gerontology concerned with the biological aging process, its evolutionary origins, and potential means to intervene in the process. The term "biogerontology" was coined by S. Rattan, and came in regular use wit ...
* Biological immortality
* Biomarkers of ageing
Biomarkers of aging are biomarkers that could predict functional capacity at some later age better than chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological ...
* Clinical geropsychology #REDIRECT Clinical geropsychology
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* Death
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
* DNA damage theory of aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear ...
* Epigenetic clock
* Evolution of ageing
Enquiry into the evolution of ageing, or aging, aims to explain why a detrimental process such as ageing would evolve, and why there is so much variability in the lifespans of organisms. The classical theories of evolution (mutation accumulation, ...
* Genetics of ageing
Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.
The first mutation found to increase longevity in an animal was the '' ...
* Gerontechnology
Gerontechnology is an inter- and multidisciplinary academic and professional field combining gerontology and technology. Sustainability of an aging society depends upon our effectiveness in creating technological environments, including assistive ...
* Gerontology
* Gerascophobia
Gerascophobia is an abnormal or incessant fear of growing older or ageing (senescence).
Background
Gerascophobia is a clinical phobia generally classified under specific phobias or fears of a single specific panic trigger. Gerascophobia may be ...
* List of life extension-related topics
Following is a list of topics related to life extension:
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* ACE inhibitor
* Actuarial escape velocity
* Adenosine triphosphate (ATP)
* Advanced Cell Technology Corporation
* Aerobic exercise
* Age-adjusted life expectancy
* Ageles ...
* Longevity
The word " longevity" is sometimes used as a synonym for "life expectancy" in demography. However, the term ''longevity'' is sometimes meant to refer only to especially long-lived members of a population, whereas ''life expectancy'' is always d ...
* Mitochondrial theory of ageing
The mitochondrial theory of ageing has two varieties: free radical and non-free radical. The first is one of the variants of the free radical theory of ageing. It was formulated by J. Miquel and colleagues in 1980 and was developed in the works of ...
* Neuroscience of ageing
* Old age
Old age refers to ages nearing or surpassing the life expectancy of human beings, and is thus the end of the human life cycle. Terms and euphemisms for people at this age include old people, the elderly (worldwide usage), OAPs (British usage ...
* Population ageing
Population ageing is an increasing median age in a population because of declining fertility rates and rising life expectancy. Most countries have rising life expectancy and an ageing population, trends that emerged first in developed countries b ...
* Progeria
Progeria is a specific type of progeroid syndrome, also known as Hutchinson–Gilford syndrome. A single gene mutation is responsible for progeria. The gene, known as lamin A (LMNA), makes a protein necessary for holding the Nucleus of the cell ...
* Rejuvenation
Rejuvenation is a medical discipline focused on the practical reversal of the aging process.
Rejuvenation is distinct from life extension. Life extension strategies often study the causes of aging and try to oppose those causes in order to slow ...
* Stem cell theory of ageing
* Supercentenarian
A supercentenarian (sometimes hyphenated as super-centenarian) is a person who has reached the age of 110 years. This age is achieved by about one in 1,000 centenarians. Supercentenarians typically live a life free of major age-related diseases u ...
* Transgenerational design
Transgenerational design is the practice of making products and environments compatible with those physical and sensory impairments associated with human aging and which limit major activities of daily living. The term ''transgenerational design ...
References
External links
Ageing and Death in Folklore
Age Calculator Online
Global AgeWatch
Statistics on population ageing and life expectancy
* HelpAge International and UNFPA (2012)
Ageing in the 21st Century – A Celebration and a Challenge.
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Gerontology
Old age