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 a limited amount of resources that it can allocate to its various
cellular processes
The cell is the basic structural and functional unit of life forms. Every cell consists of a cytoplasm enclosed within a membrane, and contains many biomolecules such as proteins, DNA and RNA, as well as many small molecules of nutrients and ...
. Therefore, a greater investment in growth and reproduction would result in reduced investment in DNA repair maintenance, leading to increased
cellular damage,
shortened telomeres, accumulation of
mutations, compromised
stem cells
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 of ...
, and ultimately,
senescence. Although many models, both animal and human, have appeared to support this theory, parts of it are still controversial.
Specifically, while the
evolutionary trade-off between
growth and aging has been well established,
the relationship between reproduction and aging is still without
scientific consensus, and the cellular mechanisms largely undiscovered.
Background and history
British biologist Thomas Kirkwood first proposed the disposable soma theory of aging in a 1977
''Nature'' review article.
The theory was inspired by
Leslie Orgel's Error Catastrophe Theory of Aging, which was published fourteen years earlier, in 1963. Orgel believed that the process of aging arose due to mutations acquired during the replication process, and Kirkwood developed the disposable soma theory in order to mediate Orgel's work with
evolutionary genetics
Population genetics is a subfield of genetics that deals with genetic differences within and between populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and popu ...
.
Principles
The disposable soma theory of aging posits that there is a trade-off in
resource allocation
In economics, resource allocation is the assignment of available resources to various uses. In the context of an entire economy, resources can be allocated by various means, such as markets, or planning.
In project management, resource allocati ...
between
somatic maintenance and
reproductive investment. Too low an investment in self-repair would be evolutionarily unsound, as the organism would likely die before reproductive age. However, too high an investment in self-repair would also be
evolutionarily unsound due to the fact that one's
offspring would likely die before reproductive age. Therefore, there is a compromise and resources are partitioned accordingly. However, this compromise is thought to damage somatic repair systems, which can lead to
progressive cellular damage and senescence. Repair costs can be categorized into three groups: (1) the costs of increased
durability of nonrenewable parts; (2) the costs of maintenance involving
cell renewal, and (3) the costs of intracellular maintenance. In a nutshell,
aging and decline is essentially a trade-off for increased reproductive robustness in youth.
Mechanisms
Growth and somatic maintenance
Much research has been done on the antagonistic effects of increased growth on lifespan. Specifically, the hormone
insulin-like growth factor 1
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.
IGF-1 is a protein that in humans ...
(IGF-1), binds to a cell receptor, leading to a
phosphorylation cascade
A phosphorylation cascade is a sequence of signaling pathway events where one enzyme phosphorylates another, causing a chain reaction leading to the phosphorylation of thousands of proteins. This can be seen in signal transduction of hormone mess ...
. This cascade results in kinases phosphorylating
forkhead transcription factor (FOXO), deactivating it. Deactivation of FOXO results in an inability to express genes involved in responding to
oxidative stress response, such as
antioxidants
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 lubricants, ...
,
chaperones, and
heat-shock proteins
Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...
.
Additionally, uptake of IGF-1 stimulates the
mTOR
The mammalian target of 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 ''MTOR'' gene. ...
pathway, which activates protein synthesis (and therefore growth) through upregulation of the translation-promoting
S6K1
Ribosomal protein S6 kinase beta-1 (S6K1), also known as p70S6 kinase (p70S6K, p70-S6K), is an enzyme (specifically, a protein kinase) that in humans is encoded by the ''RPS6KB1'' gene. It is a serine/threonine kinase that acts downstream of PIP3 ...
, and also inhibits
autophagy, a process necessary for recycling of damaged cellular products. Decline of autophagy causes
neurodegeneration,
protein aggregation
In molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate (i.e., accumulate and clump together) either intra- or extracellularly. Protein aggregates have been implicated in a wi ...
and
premature aging
Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term ''progeroid syndrome'' does not necessarily imply progeria (Hutchinson–Gilford ...
. Lastly, studies have also indicated that the mTOR pathway also alters
immune responses
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
and stimulates
cyclin-dependent kinase (CDK) inhibitors such as
p16
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 ...
and
p21. This leads to alteration of the
stem-cell niche and results in
stem cell exhaustion, another theorized mechanism of aging.
Reproduction and somatic maintenance
While reproduction inhibits lifespan with regard to multicellular organisms, the precise mechanism responsible for this effect remains unclear. Although many models do illustrate an inverse relationship, and the theory makes sense from an evolutionary perspective,
the cellular mechanisms have yet to be explored. However, with regards to
cellular replication, the progressive shortening of telomeres is a mechanism which
limits the amount of generations of a single cell may undergo. Furthermore, in unicellular organisms like ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
'', the formation of
extrachromosomal rDNA circle
Extrachromosomal rDNA circles (aka ERC) are pieces of extrachromosomal circular DNA (eccDNA) derived from ribosomal DNA (rDNA). Initially found in baker's yeast, these self-replicating circles are suggested to contribute to their aging and found i ...
s (ERCs) in mother cells (but not daughter cells) upon every subsequent division is an identifiable type of DNA damage that is associated with replication. These ERCs accumulate over time and eventually trigger replicative senescence and death of the mother cell.
Evidence
Growth and aging
There is a large body of evidence indicating the negative effects of growth on longevity across many species. As a general rule, individuals of a smaller size generally live longer than larger individuals of the same species.
Animal models
In
dwarf
Dwarf or dwarves may refer to:
Common uses
*Dwarf (folklore), a being from Germanic mythology and folklore
* Dwarf, a person or animal with dwarfism
Arts, entertainment, and media Fictional entities
* Dwarf (''Dungeons & Dragons''), a humanoid ...
models of
mice, such Snell or Ames mice, mutations have arisen, either rendering them incapable of producing IGF-1 or unable to have adequate receptors for IGF-1 uptake. Furthermore, mice injected with growth hormone have been shown to have progressive weight loss, roughing of the coat,
curvature of the spine
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not ty ...
,
enlargement of the organs, kidney lesions and
increased cancer risk. This effect is also seen in different breeds of
dogs, where smaller breeds of dogs typically live significantly longer compared to their larger counterparts. Selectively bred for their small size, smaller dog breeds like the
Chihuahua (average lifespan of 15–20 years) have the B/B genotype for the IGF-1
haplotype, reducing the amount of IGF-1 produced. Conversely, large dogs like the
Great Dane
The Great Dane is a large sized dog breed originating from Germany. The Great Dane descends from hunting dogs from the Middle Ages used to hunt wild boar and deer, and as guardians of German nobility. It is one of the largest breeds in the worl ...
(average lifespan of 6–8 years) are
homozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
for the IGF-1 I
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
, which increases the amount of IGF-1 production.
Human models
Initially, it was believed that growth hormone actually prolonged lifespan due to a 1990 study that indicated that injection of
growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
to men over 60 years of age appeared to reverse various
biomarkers
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, pa ...
implicated in aging, such as
decreased muscle mass, bone density, skin thickness, and increased adipose tissue. However, a 1999 study found that administering growth hormone also significantly increased
mortality rate
Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of d ...
. Recent
genomic studies have confirmed that the genes involved in growth hormone uptake and signaling are largely conserved across a plethora of species, such as yeast, nematodes, fruit flies, mice and humans. These studies have also shown that individuals with
Laron syndrome
Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1; somatomedin) production in response t ...
, an
autosomal recessive disorder resulting in dwarfism due to defects in growth hormone receptors, have increased lifespan. Additionally, these individuals have much lower
incidences of age-related diseases such as
type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...
and cancer. Lastly, 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 ...
around the world are disproportionately of
short stature
Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ' ...
, and have low levels of IGF-1.
Reproduction and aging
Numerous studies have found that lifespan is inversely correlated with both the total amount of offspring birthed, as well as the age at which females first gives birth, also known as primiparity.
Additionally, it has been found that
reproduction is a costly mechanism that alters the
metabolism of fat.
Lipids
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
invested in reproduction would be unable to be allocated to support mechanisms involved in somatic maintenance.
Animal models
The disposable soma theory has been consistent with the majority of animal models. It was found in numerous animal studies that
castration
Castration is any action, surgical, chemical, or otherwise, by which an individual loses use of the testicles: the male gonad. Surgical castration is bilateral orchiectomy (excision of both testicles), while chemical castration uses pharma ...
or
genetic deformities of
reproduction organs was
correlated
In statistics, correlation or dependence is any statistical relationship, whether causal or not, between two random variables or bivariate data. Although in the broadest sense, "correlation" may indicate any type of association, in statistic ...
with increased lifespan. Moreover, in
red squirrels
The red squirrel (''Sciurus vulgaris'') is a species of tree squirrel in the genus ''Sciurus'' common throughout Europe and Asia. The red squirrel is an arboreal, primarily herbivorous rodent.
In Great Britain, Ireland, and in Italy numbers ...
, it was found that females with an early primiparity achieved the highest immediate and lifetime reproductive success. However, it was also found that these same individuals had a decreased median and maximum lifespan. Specifically squirrels who mated earlier had a 22.4% rate of mortality until two years of age compared to a 16.5% rate of mortality in late breeders. In addition, these squirrels had an average maximum lifespan of 1035 days compared to an average maximum lifespan of 1245 days for squirrels that bred later.
In another study, researchers selectively bred
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 ...
over three years to develop two different
strain
Strain may refer to:
Science and technology
* Strain (biology), variants of plants, viruses or bacteria; or an inbred animal used for experimental purposes
* Strain (chemistry), a chemical stress of a molecule
* Strain (injury), an injury to a mu ...
s, an early-reproducing strain and a late-reproducing strain. The late-reproducing line had a significantly longer lifespan than the early-reproducing line. Even more telling was that when the researchers introduced a mutation in the
ovarian-associated gene ''ovoD1'', resulting in defective
oogenesis, the differences in lifespan between the two lines disappeared. The researchers in this case concluded that "aging has evolved primarily because of the damaging effects of reproduction earlier in life".
Prominent aging researcher
Steven Austad also performed a large-scale
ecological
Ecology () is the study of the relationships between living organisms, including humans, and their physical environment. Ecology considers organisms at the individual, population, community, ecosystem, and biosphere level. Ecology overlaps wi ...
study on the
coast
The coast, also known as the coastline or seashore, is defined as the area where land meets the ocean, or as a line that forms the boundary between the land and the coastline. The Earth has around of coastline. Coasts are important zones in ...
of
Georgia
Georgia most commonly refers to:
* Georgia (country), a country in the Caucasus region of Eurasia
* Georgia (U.S. state), a state in the Southeast United States
Georgia may also refer to:
Places
Historical states and entities
* Related to the ...
in 1993. Austad isolated two
opossum populations, one from the
predator
Predation is a biological interaction where one organism, the predator, kills and eats another organism, its prey. It is one of a family of common feeding behaviours that includes parasitism and micropredation (which usually do not kill th ...
-infested mainland and one from the predator-absent nearby island of
Sapelo. According to the disposable soma theory, a
genetically isolated population subject to low environmentally-induced mortality would evolve delayed reproduction and aging. This is because without the pressure of predation, it would be evolutionarily advantageous to allocate more resources to somatic maintenance than reproduction, as early offspring mortality would be low. As predicted, even after controlling for predation, the isolated population had a longer lifespan, delayed primiparity, and reduced aging biomarkers such as tail
collagen cross-linking.
Human models
In general, only a few studies exist in human models. It was found that
castrated men live longer than their
fertile counterparts. Further studies found that in British women, primiparity was earliest in women who died early and latest in women who died at the oldest ages. Furthermore, increased number of children birthed was associated with a decreased lifespan. A final study found that female centenarians were more likely to have children in later life compared average, especially past the age of 40. The researchers discovered that 19.2% of female centenarians had their first child after the age of 40, compared to 5.5% of the rest of the female population.
Relationship between cell damage and aging
![Naked Mole Rat Eating](https://upload.wikimedia.org/wikipedia/commons/c/cf/Naked_Mole_Rat_Eating.jpg)
There are numerous studies that support cellular damage, often due to a lack of somatic maintenance mechanisms, as a primary determinant for aging, and these studies have given rise to the
free radical theory of aging and the
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 D ...
. One study found that the cells of short-living rodents ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' show much greater
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 replication, DNA or viral repl ...
rates and a general lack of genome surveillance compared to human cells and are far more susceptible to
oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
.
Other studies have been conducted on the
naked mole rat
The naked mole-rat (''Heterocephalus glaber''), also known as the sand puppy, is a burrowing rodent native to the Horn of Africa and parts of Kenya, notably in Somali regions. It is closely related to the blesmols and is the only species in the ...
, a rodent species with remarkable longevity (30 years), capable of outliving the
brown rat
The brown rat (''Rattus norvegicus''), also known as the common rat, street rat, sewer rat, wharf rat, Hanover rat, Norway rat, Norwegian rat and Parisian rat, is a widespread species of common rat. One of the largest muroids, it is a brown o ...
(3 years) by
ten-fold. Additionally, almost no incidence of cancer has ever been detected in naked mole rats. Nearly all of the differences found between these two organisms, which are otherwise rather genetically similar, was in somatic maintenance. Naked mole rats were found to have higher levels of
superoxide dismutase, a
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 ...
clearing
antioxidant. In addition, naked mole rats had higher levels of
base excision repair
Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from t ...
, DNA damage response signaling,
homologous recombination repair
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
,
mismatch repair
DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage.
Mismatch ...
,
nucleotide excision repair, and
non-homologous end joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direc ...
. In fact, many of these processes were near or exceeded human levels. Proteins from naked mole rats were also more resistant to
oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
,
misfolding
Protein folding is the physical process by which a protein chain is Translation (biology), translated to its native protein tertiary structure, three-dimensional structure, typically a "folded" Protein structure, conformation by which the prote ...
,
ubiquitination
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
, and had increased
translational fidelity.
Further studies have been conducted on patients with
Hutchinson-Gilford Progeria Syndrome (HGPS), a condition that leads to premature aging. Patients with HGPS typically age about seven times faster than average and usually succumb to the disease in their early teens. Patients with HGPS have cellular defects, specifically in the
lamin proteins, which regulate the organization of the
lamina
Lamina may refer to:
Science and technology
* Planar lamina, a two-dimensional planar closed surface with mass and density, in mathematics
* Laminar flow, (or streamline flow) occurs when a fluid flows in parallel layers, with no disruption betwee ...
and
nuclear envelope for
mitosis. A-type
lamin
Lamins, also known as nuclear lamins are fibrous proteins in type V intermediate filaments, providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form t ...
s promote genetic stability by maintaining levels of proteins that have key roles in the repair processes of
non-homologous end joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direc ...
and
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
. Mouse cells deficient for maturation of prelamin A show increased
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 d ...
and chromosome aberrations and have increased sensitivity to DNA damaging agents.
Lastly, as mentioned previously, it has been found that the suppression of autophagy is associated with reduced lifespan, while stimulation is associated with extended lifespan. Activated in times of
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 ...
, autophagy is a process that prevents cellular damage through clearance and
recycling
Recycling is the process of converting waste materials into new materials and objects. The recovery of energy from waste materials is often included in this concept. The recyclability of a material depends on its ability to reacquire the p ...
of damaged proteins and
organelles
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' th ...
.
Criticism
One of the main weaknesses of the disposable soma theory is that it does not postulate any specific cellular mechanisms to which an organism shifts energy to somatic repair over reproduction. Instead, it only offers an
evolutionary perspective on why aging may occur due to reproduction. Therefore, parts of it are rather limited outside of the field of
evolutionary biology
Evolutionary biology is the subfield of biology that studies the evolutionary processes ( natural selection, common descent, speciation) that produced the diversity of life on Earth. It is also defined as the study of the history of life ...
.
Caloric restriction
![Soma Disposable](https://upload.wikimedia.org/wikipedia/commons/c/c7/Soma_Disposable.png)
Critics have pointed out the supposed
inconsistencies of the disposable soma theory due to the observed effects of caloric restriction, which is correlated with increased lifespan. Although it activates autophagy, according to classical disposable soma principles, with less
caloric intake
The calorie is a unit of energy. For historical reasons, two main definitions of "calorie" are in wide use. The large calorie, food calorie, or kilogram calorie was originally defined as the amount of heat needed to raise the temperature of on ...
, there would less total energy to be distributed towards somatic maintenance, and decreased lifespan would be observed (or at least the positive autophagic effects would be balanced out). However, Kirkwood, alongside his collaborator Darryl P. Shanley, assert that caloric restriction triggers an adaptive mechanism which causes the organism to shift a higher proportion of resources to somatic maintenance, away from reproduction. This theory is supported by multiple studies, which show that caloric restriction typically results in
impaired fertility, but leave an otherwise healthy organism. Evolutionarily, an organism would want to delay reproduction to when resources were more plentiful. During a resource-barren period, it would evolutionarily unwise to invest resources in progeny that would be unlikely to survive in
famine
A famine is a widespread scarcity of food, caused by several factors including war, natural disasters, crop failure, population imbalance, widespread poverty, an economic catastrophe or government policies. This phenomenon is usually accompani ...
. Mechanistically, the
NAD-dependent
deacetylase Sirtuin 1 (SIRT-1) is upregulated during low-nutrient periods. SIRT-1 increases
insulin sensitivity
Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar) ...
, decreases the amount of
inflammatory cytokine An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule (a cytokine) that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include int ...
s, stimulates autophagy, and activates FOXO, the aforementioned protein involved in activating stress response genes. SIRT-1 is also found to result in decreased fertility.
In additional to differential
partitioning of energy allocation during caloric restriction, less caloric intake would result in less metabolic waste in the forms of
free radicals like
hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%â ...
,
superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
and
hydroxyl radicals
The hydroxyl radical is the diatomic molecule . The hydroxyl radical is very stable as a dilute gas, but it decays very rapidly in the condensed phase. It is pervasive in some situations. Most notably the hydroxyl radicals are produced from the ...
, which damage important cellular components, particularly
mitochondria. Elevated levels of free radicals in mice has been correlated with neurodegeneration,
myocardial injury,
severe anemia, and premature death.
No changes were observed in the spontaneous
chromosomal
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
mutation frequency of dietary restricted mice (aged 6 and 12 months) compared to ''ad libitum'' fed control mice. Thus dietary restriction appears to have no appreciable effect on spontaneous mutation in chromosomal DNA, and the increased longevity of dietary restricted mice apparently is not attributable to reduced chromosomal mutation frequency.
The grandmother hypothesis
Another primary criticism of the disposable soma theory is that it fails to account for why women tend to live longer than their male counterparts. Afterall, females invest significantly more resources into reproduction and according to the classical disposable soma principles, this would compromise energy diverted to somatic maintenance. However, this can be reconciled with the
grandmother hypothesis
The grandmother hypothesis is a hypothesis to explain the existence of menopause in human life history by identifying the adaptive value of extended kin networking. It builds on the previously postulated " mother hypothesis" which states that as m ...
. The Grandmother Hypothesis states that
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 ...
comes about into older women in order to restrict the time of reproduction as a protective mechanism. This would allow women to live longer and increase the amount of care they could provide to their
grandchildren
Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Ideall ...
, increasing their evolutionary fitness. And so, although women do invest a greater proportion of resources into reproduction during their
fertile years, their overall reproductive period is significantly shorter than men, who are able of reproduction during and even beyond
middle age. Additionally, males invest more resources into growth compare to females, which is correlated with decreased lifespan. Other variables such as increased
testosterone levels in males are not accounted for. Increased testosterone is often associated with reckless behaviour, which may lead to a high accidental death rate.
Contradicting models
A few
contradicting animal models weaken the validity of the disposable soma theory. This includes studies done on the aforementioned naked mole rats. In these studies, it was found that reproductive naked mole rats actually show significantly increased lifespans compared to non-reproductive individuals, which contradicts the principles of disposable soma. However, although these naked mole rats are
mammalian
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...
, they are highly atypical in terms of aging studies and may not serve as the best model for humans. For example, naked mole rats have a disproportionately high longevity quotient and live in
eusocial societies, where breeding is usually designated to a
queen
Queen or QUEEN may refer to:
Monarchy
* Queen regnant, a female monarch of a Kingdom
** List of queens regnant
* Queen consort, the wife of a reigning king
* Queen dowager, the widow of a king
* Queen mother, a queen dowager who is the mother ...
.
Sex biases and environment
The disposable soma theory is tested disproportionately on female organisms for the relationship between reproduction and aging, as
females carry a greater burden in reproduction. Additionally, for the relationship between growth and aging, studies are disproportionately conducted on males, to minimize the
hormonal fluctuations that occur with
menstrual cycling. Lastly,
genetic and
environmental factors, rather than reproductive patterns, may explain the variations in human lifespan. For example, studies have shown that
poorer individuals, to whom nutritious food and
medical care
Health care or healthcare is the improvement of health via the prevention, diagnosis, treatment, amelioration or cure of disease, illness, injury, and other physical and mental impairments in people. Health care is delivered by health p ...
is less accessible, typically have higher birth rates and earlier primiparity.
References
External links
Calorie restriction
Calorie Restriction Society
Biology of aging
€”Includes a discussion of the free radical theory of aging
{{DEFAULTSORT:Free-Radical Theory
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Evolution
Proximate theories of biological ageing
Senescence
Theories of ageing
Theories of biological ageing