Senescent
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Senescent
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 involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle. Senescence is the inevitable fate of almost all multicellular organisms with germ-soma separation, but it can be delayed. The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats, and the existence of species having negligible senescence and potentially immortal organisms such as '' Hydra'', have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases. Environmental factors may affect aging – for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body may ...
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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 approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence", or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things. The physiological importance for cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair. Senescent cells contribute to the aging phenotype, including frailty syndrom ...
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Hallmarks Of Aging
The hallmarks of aging are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first enumerated in a landmark paper in 2013 to conceptualize the essence of biological aging and its underlying mechanisms. Overview Over time, almost all living organisms experience a gradual and irreversible increase in senescence and an associated loss of proper function of the bodily systems. As aging is the primary risk factor for major human diseases, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases, it is important to describe and classify the types of changes that it entails. The nine hallmarks of aging are grouped into three categories as follows: Primary hallmarks (causes of damage) * Genome instability * Telomere shortening * Epigenetic alterations * Loss of proteostasis Antagonistic hallmarks (respon ...
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Aging
Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants 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, Alzheimer's disease, diabetes, cardiovascular disease, stroke 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 ox ...
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Ann Pouder
American supercentenarians are citizens or residents of the United States who have attained or surpassed 110 years of age. , the Gerontology Research Group (GRG) had validated the longevity claims of 782 American supercentenarians. As of , it lists the oldest living American-born person as Spanish emigrant María Branyas Morera (born in San Francisco, California on March 4, 1907), aged . The oldest American resident is listed as Edie Ceccarelli (born in Willits, California on February 5, 1908), aged . The longest-lived person ever from the United States is Sarah Knauss, of Hollywood, Luzerne County, Pennsylvania, who died on December 30, 1999, aged 119 years and 97 days. 100 oldest known Americans Below is a list of the 100 longest lived American supercentenarians according to the GRG and reliable sourcing. Biographies Ann Pouder Ann Pouder (née Ann Marie Alexander; April 8, 1807 – July 10, 1917) was one of the first modern recognized supercentenarians, living to ...
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Skin Aging
The human skin is the outer covering of the body and is the largest organ of the integumentary system. The skin has up to seven layers of ectodermal tissue guarding muscles, bones, ligaments and internal organs. Human skin is similar to most of the other mammals' skin, and it is very similar to pig skin. Though nearly all human skin is covered with hair follicles, it can appear hairless. There are two general types of skin, hairy and glabrous skin (hairless). The adjective ''cutaneous'' literally means "of the skin" (from Latin ''cutis'', skin). Because it interfaces with the environment, skin plays an important immunity role in protecting the body against pathogens and excessive water loss. Its other functions are insulation, temperature regulation, sensation, synthesis of vitamin D, and the protection of vitamin B folates. Severely damaged skin will try to heal by forming scar tissue. This is often discoloured and depigmented. In humans, skin pigmentation (affected by m ...
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Nutrient Sensing
Nutrient sensing is a cell's ability to recognize and respond to fuel substrates such as glucose. Each type of fuel used by the cell requires an alternate pathway of utilization and accessory molecules. In order to conserve resources a cell will only produce molecules that it needs at the time. The level and type of fuel that is available to a cell will determine the type of enzymes it needs to express from its genome for utilization. Receptors on the cell membrane's surface designed to be activated in the presence of specific fuel molecules communicate to the cell nucleus via a means of cascading interactions. In this way the cell is aware of the available nutrients and is able to produce only the molecules specific to that nutrient type. Nutrient Sensing in Mammalian Cells A rapid and efficient response to disturbances in nutrient levels is crucial for the survival of organisms from bacteria to humans. Cells have therefore evolved a host of molecular pathways that can sense ...
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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 present within and outside the cell. Loss of proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes, as well as aggregation-associated degenerative disorders. Therapeutic restoration of proteostasis may treat or resolve these pathologies. Cellular proteostasis is key to ensuring successful development, healthy aging, resistance to environmental stresses, and to minimize homeostatic perturbations from pathogens such as viruses. Cellular mechanisms for maintaining proteostasis include regulated protein translation, chaperone assisted protein folding, and protein degradation pathways. Adjusting each of these mechanisms based on the need f ...
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Epigenetics
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in addition to" the traditional genetic basis for inheritance. Epigenetics most often involves changes that affect the regulation of gene expression, but the term can also be used to describe any heritable phenotypic change. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors, or be part of normal development. The term also refers to the mechanism of changes: functionally relevant alterations to the genome that do not involve mutation of the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression c ...
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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 most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break. Discovery In the early 1970s, Soviet theorist Alexei Olovnikov first recognized that chromosomes could not completely replicate their ends; this is known as the "end replication problem". Building on this, and accommodating Leonard Hayflick's idea of limited somatic cell division, Olovnikov suggested that DNA sequences are lost every time a cell replicates until the loss reaches a critical level, at which point cell division end ...
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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 aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy. The sources of genome instability have only recently begun to be elucidated. A high frequency of externally caused DNA damage can be one source of genome instability since DNA damage can cause inaccurate translesion DNA synthesis past the damage or errors in repair, leading to mutation. Another source of genome instability may be epigenetic or mutational reductions in expression of DNA repair genes. Because endogenous (metabolically-caused) DNA damage is very fr ...
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Heart 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, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis. The underlying mechanisms vary depending on the disease. It is estimated that dietary risk factors are associated with 53% of CVD deaths. Coronary artery disease, stroke, and peripheral artery disease involve atherosclerosis. This may be caused by high blood pressure, smoking, diabetes mellitus, lack of exercise, obesity, high blood cholesterol, poor diet, excessive alcohol consumption, and poor sleep, among other things. High blood pressure is estimated to account for approximatel ...
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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 bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of ...
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