fbpx
Wikipedia

Senescence

January 09, 2024

This article is about the aging of whole organisms including animals. For aging specifically in humans, see Aging. For plants, see Plant senescence. For cells that stop dividing, see Cellular senescence. For bacteria, see Bacterial senescence.

Senescence (/sɪˈnɛsəns/) 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 later part of an organism's life cycle.[1][2] However, the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can extend lifespans by 50% in rats, the existence of species having negligible senescence, and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.

Supercentenarian Ann Pouder (8 April 1807 – 10 July 1917) photographed on her 110th birthday. A heavily lined face is common in human senescence.

Environmental factors may affect aging – for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body may age at different rates and distinctly, including the brain, the cardiovascular system, and muscle. Similarly, functions may distinctly decline with aging, including movement control and memory. Two organisms of the same species can also age at different rates, making biological aging and chronological aging distinct concepts.

Definition and characteristics edit

Organismal senescence is the aging of whole organisms. Actuarial senescence can be defined as an increase in mortality and/or a decrease in fecundity with age. The Gompertz–Makeham law of mortality says that the age-dependent component of the mortality rate increases exponentially with age.

Aging is characterized by the declining ability to respond to stress, increased homeostatic imbalance, and increased risk of aging-associated diseases including cancer and heart disease. Aging has been defined as "a progressive deterioration of physiological function, an intrinsic age-related process of loss of viability and increase in vulnerability."[3]

In 2013, a group of scientists defined nine hallmarks of aging that are common between organisms with emphasis on mammals:

In a decadal update, three hallmarks have been added, totaling 12 proposed hallmarks:

The environment induces damage at various levels, e.g. damage to DNA, and damage to tissues and cells by oxygen radicals (widely known as free radicals), and some of this damage is not repaired and thus accumulates with time.[6] Cloning from somatic cells rather than germ cells may begin life with a higher initial load of damage. Dolly the sheep died young from a contagious lung disease, but data on an entire population of cloned individuals would be necessary to measure mortality rates and quantify aging.[citation needed]

The evolutionary theorist George Williams wrote, "It is remarkable that after a seemingly miraculous feat of morphogenesis, a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed."[7]

Variation among species edit

Further information: Longevity § Non-human biological longevity

Different speeds with which mortality increases with age correspond to different maximum life span among species. For example, a mouse is elderly at 3 years, a human is elderly at 80 years,[8] and ginkgo trees show little effect of age even at 667 years.[9]

Almost all organisms senesce, including bacteria which have asymmetries between "mother" and "daughter" cells upon cell division, with the mother cell experiencing aging, while the daughter is rejuvenated.[10][11] There is negligible senescence in some groups, such as the genus Hydra.[12] Planarian flatworms have "apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult stem cells."[13] These planarians are not biologically immortal, but rather their death rate slowly increases with age. Organisms that are thought to be biologically immortal would, in one instance, be Turritopsis dohrnii, also known as the "immortal jellyfish", due to its ability to revert to its youth when it undergoes stress during adulthood.[14] The reproductive system is observed to remain intact, and even the gonads of Turritopsis dohrnii are existing.[15]

Some species exhibit "negative senescence", in which reproduction capability increases or is stable, and mortality falls with age, resulting from the advantages of increased body size during aging.[16]

Theories of aging edit

More than 300 different theories have been posited to explain the nature (mechanisms) and causes (reasons for natural emergence or factors) of aging.[17][additional citation(s) needed] Good theories would both explain past observations and predict the results of future experiments. Some of the theories may complement each other, overlap, contradict, or may not preclude various other theories.[citation needed]

Theories of aging fall into two broad categories, evolutionary theories of aging and mechanistic theories of aging. Evolutionary theories of aging primarily explain why aging happens,[18] but do not concern themselves with the molecular mechanism(s) that drive the process. All evolutionary theories of aging rest on the basic mechanisms that the force of natural selection declines with age.[19][20] Mechanistic theories of aging can be divided into theories that propose aging is programmed, and damage accumulation theories, i.e. those that propose aging to be caused by specific molecular changes occurring over time.

This section is an excerpt from Stem cell theory of aging § Other theories of aging.[edit]
The aging process can be explained with different theories. These are evolutionary theories, molecular theories, system theories and cellular theories. The evolutionary theory of ageing was first proposed in the late 1940s and can be explained briefly by the accumulation of mutations (evolution of ageing), disposable soma and antagonistic pleiotropy hypothesis. The molecular theories of ageing include phenomena such as gene regulation (gene expression), codon restriction, error catastrophe, somatic mutation, accumulation of genetic material (DNA) damage (DNA damage theory of aging) and dysdifferentiation. The system theories include the immunologic approach to ageing, rate-of-living and the alterations in neuroendocrinal control mechanisms. (See homeostasis). Cellular theory of ageing can be categorized as telomere theory, free radical theory (free-radical theory of aging) and apoptosis. The stem cell theory of aging is also a sub-category of cellular theories.

Evolutionary aging theories edit

Main article: Evolution of ageing

Antagonistic pleiotropy edit

Main article: Antagonistic pleiotropy hypothesis

One theory was proposed by George C. Williams[7] and involves antagonistic pleiotropy. A single gene may affect multiple traits. Some traits that increase fitness early in life may also have negative effects later in life. But, because many more individuals are alive at young ages than at old ages, even small positive effects early can be strongly selected for, and large negative effects later may be very weakly selected against. Williams suggested the following example: Perhaps a gene codes for calcium deposition in bones, which promotes juvenile survival and will therefore be favored by natural selection; however, this same gene promotes calcium deposition in the arteries, causing negative atherosclerotic effects in old age. Thus, harmful biological changes in old age may result from selection for pleiotropic genes that are beneficial early in life but harmful later on. In this case, selection pressure is relatively high when Fisher's reproductive value is high and relatively low when Fisher's reproductive value is low.

Cancer versus cellular senescence tradeoff theory of aging edit

Main article: Immunosenescence

Senescent cells within a multicellular organism can be purged by competition between cells, but this increases the risk of cancer. This leads to an inescapable dilemma between two possibilities—the accumulation of physiologically useless senescent cells, and cancer—both of which lead to increasing rates of mortality with age.[2]

Disposable soma edit

Main article: Disposable soma theory of aging

The disposable soma theory of aging was proposed by Thomas Kirkwood in 1977.[1][21] The theory suggests that aging occurs due to a strategy in which an individual only invests in maintenance of the soma for as long as it has a realistic chance of survival.[22] A species that uses resources more efficiently will live longer, and therefore be able to pass on genetic information to the next generation. The demands of reproduction are high, so less effort is invested in repair and maintenance of somatic cells, compared to germline cells, in order to focus on reproduction and species survival.[23]

Programmed aging theories edit

Programmed theories of aging posit that aging is adaptive, normally invoking selection for evolvability or group selection.

The reproductive-cell cycle theory suggests that aging is regulated by changes in hormonal signaling over the lifespan.[24]

Damage accumulation theories edit

The free radical theory of aging edit

Main article: Free-radical theory of aging

One of the most prominent theories of aging was first proposed by Harman in 1956.[25] It posits that free radicals produced by dissolved oxygen, radiation, cellular respiration and other sources cause damage to the molecular machines in the cell and gradually wear them down. This is also known as oxidative stress.

There is substantial evidence to back up this theory. Old animals have larger amounts of oxidized proteins, DNA and lipids than their younger counterparts.[26][27]

Chemical damage edit

 
Elderly Klamath woman photographed by Edward S. Curtis in 1924
See also: DNA damage theory of aging

One of the earliest aging theories was the Rate of Living Hypothesis described by Raymond Pearl in 1928[28] (based on earlier work by Max Rubner), which states that fast basal metabolic rate corresponds to short maximum life span.

While there may be some validity to the idea that for various types of specific damage detailed below that are by-products of metabolism, all other things being equal, a fast metabolism may reduce lifespan, in general this theory does not adequately explain the differences in lifespan either within, or between, species. Calorically restricted animals process as much, or more, calories per gram of body mass, as their ad libitum fed counterparts, yet exhibit substantially longer lifespans.[citation needed] Similarly, metabolic rate is a poor predictor of lifespan for birds, bats and other species that, it is presumed, have reduced mortality from predation, and therefore have evolved long lifespans even in the presence of very high metabolic rates.[29] In a 2007 analysis it was shown that, when modern statistical methods for correcting for the effects of body size and phylogeny are employed, metabolic rate does not correlate with longevity in mammals or birds.[30]

With respect to specific types of chemical damage caused by metabolism, it is suggested that damage to long-lived biopolymers, such as structural proteins or DNA, caused by ubiquitous chemical agents in the body such as oxygen and sugars, are in part responsible for aging. The damage can include breakage of biopolymer chains, cross-linking of biopolymers, or chemical attachment of unnatural substituents (haptens) to biopolymers.[citation needed] Under normal aerobic conditions, approximately 4% of the oxygen metabolized by mitochondria is converted to superoxide ion, which can subsequently be converted to hydrogen peroxide, hydroxyl radical and eventually other reactive species including other peroxides and singlet oxygen, which can, in turn, generate free radicals capable of damaging structural proteins and DNA.[6] Certain metal ions found in the body, such as copper and iron, may participate in the process. (In Wilson's disease, a hereditary defect that causes the body to retain copper, some of the symptoms resemble accelerated senescence.) These processes termed oxidative stress are linked to the potential benefits of dietary polyphenol antioxidants, for example in coffee,[31] and tea.[32] However their typically positive effects on lifespans when consumption is moderate[33][34][35] have also been explained by effects on autophagy,[36] glucose metabolism[37] and AMPK.[38]

Sugars such as glucose and fructose can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts, in a process called glycation. These adducts can further rearrange to form reactive species, which can then cross-link the structural proteins or DNA to similar biopolymers or other biomolecules such as non-structural proteins. People with diabetes, who have elevated blood sugar, develop senescence-associated disorders much earlier than the general population, but can delay such disorders by rigorous control of their blood sugar levels. There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation.

Free radicals can damage proteins, lipids or DNA. Glycation mainly damages proteins. Damaged proteins and lipids accumulate in lysosomes as lipofuscin. Chemical damage to structural proteins can lead to loss of function; for example, damage to collagen of blood vessel walls can lead to vessel-wall stiffness and, thus, hypertension, and vessel wall thickening and reactive tissue formation (atherosclerosis); similar processes in the kidney can lead to kidney failure. Damage to enzymes reduces cellular functionality. Lipid peroxidation of the inner mitochondrial membrane reduces the electric potential and the ability to generate energy. It is probably no accident that nearly all of the so-called "accelerated aging diseases" are due to defective DNA repair enzymes.[39][40]

DNA damage was proposed in a 2021 review to be the underlying cause of aging because of the mechanistic link of DNA damage to nearly every aspect of the aging phenotype.[41] DNA damage-induced epigenetic alterations, such as DNA methylation and many histone modifications, appear to be of particular importance to the aging process.[41] Evidence for the theory that DNA damage is the fundamental cause of aging was first reviewed in 1981.[42]

It is believed that the impact of alcohol on aging can be partly explained by alcohol's activation of the HPA axis, which stimulates glucocorticoid secretion, long-term exposure to which produces symptoms of aging.[43]

Mutation accumulation edit

Main article: Mutation accumulation theory

Natural selection can support lethal and harmful alleles, if their effects are felt after reproduction. The geneticist J. B. S. Haldane wondered why the dominant mutation that causes Huntington's disease remained in the population, and why natural selection had not eliminated it. The onset of this neurological disease is (on average) at age 45 and is invariably fatal within 10–20 years. Haldane assumed that, in human prehistory, few survived until age 45. Since few were alive at older ages and their contribution to the next generation was therefore small relative to the large cohorts of younger age groups, the force of selection against such late-acting deleterious mutations was correspondingly small. Therefore, a genetic load of late-acting deleterious mutations could be substantial at mutation–selection balance. This concept came to be known as the selection shadow.[44]

Peter Medawar formalised this observation in his mutation accumulation theory of aging.[45][46] "The force of natural selection weakens with increasing age—even in a theoretically immortal population, provided only that it is exposed to real hazards of mortality. If a genetic disaster... happens late enough in individual life, its consequences may be completely unimportant". Age-independent hazards such as predation, disease, and accidents, called 'extrinsic mortality', mean that even a population with negligible senescence will have fewer individuals alive in older age groups.

Other damage edit

A study concluded that retroviruses in the human genomes can become awakened from dormant states and contribute to aging which can be blocked by neutralizing antibodies, alleviating "cellular senescence and tissue degeneration and, to some extent, organismal aging".[47]

Stem cell theories of aging edit

This section is an excerpt from Stem cell theory of aging.[edit]

The stem cell theory of aging postulates that the aging process is the result of the inability of various types of stem cells to continue to replenish the tissues of an organism with functional differentiated cells capable of maintaining that tissue's (or organ's) original function. Damage and error accumulation in genetic material is always a problem for systems regardless of the age. The number of stem cells in young people is very much higher than older people and thus creates a better and more efficient replacement mechanism in the young contrary to the old. In other words, aging is not a matter of the increase in damage, but a matter of failure to replace it due to a decreased number of stem cells. Stem cells decrease in number and tend to lose the ability to differentiate into progenies or lymphoid lineages and myeloid lineages.

Maintaining the dynamic balance of stem cell pools requires several conditions. Balancing proliferation and quiescence along with homing (See niche) and self-renewal of hematopoietic stem cells are favoring elements of stem cell pool maintenance while differentiation, mobilization and senescence are detrimental elements. These detrimental effects will eventually cause apoptosis.

There are also several challenges when it comes to therapeutic use of stem cells and their ability to replenish organs and tissues. First, different cells may have different lifespans even though they originate from the same stem cells (See T-cells and erythrocytes), meaning that aging can occur differently in cells that have longer lifespans as opposed to the ones with shorter lifespans. Also, continual effort to replace the somatic cells may cause exhaustion of stem cells.[48]
Hematopoietic stem cell aging
Hematopoietic stem cells (HSCs) regenerate the blood system throughout life and maintain homeostasis.[49] DNA strand breaks accumulate in long term HSCs during aging.[50][51] This accumulation is associated with a broad attenuation of DNA repair and response pathways that depends on HSC quiescence.[51] DNA ligase 4 (Lig4) has a highly specific role in the repair of double-strand breaks by non-homologous end joining (NHEJ). Lig4 deficiency in the mouse causes a progressive loss of HSCs during aging.[52] These findings suggest that NHEJ is a key determinant of the ability of HSCs to maintain themselves over time.[52]
Hematopoietic stem cell diversity aging
A study showed that the clonal diversity of stem cells that produce blood cells gets drastically reduced around age 70 to a faster-growing few, substantiating a novel theory of ageing which could enable healthy aging.[53][54]
Hematopoietic mosaic loss of chromosome Y
A 2022 study showed that blood cells' loss of the Y chromosome in a subset of cells, called 'mosaic loss of chromosome Y' (mLOY) and reportedly affecting at least 40% of 70 years-old men to some degree, contributes to fibrosis, heart risks, and mortality in a causal way.[55][56]

Biomarkers of aging edit

Main article: Biomarkers of aging

If different individuals age at different rates, then fecundity, mortality, and functional capacity might be better predicted by biomarkers than by chronological age.[57][58] However, graying of hair,[59] face aging, skin wrinkles and other common changes seen with aging are not better indicators of future functionality than chronological age. Biogerontologists have continued efforts to find and validate biomarkers of aging, but success thus far has been limited.

Levels of CD4 and CD8 memory T cells and naive T cells have been used to give good predictions of the expected lifespan of middle-aged mice.[60]

Aging clocks edit

There is interest in an epigenetic clock as a biomarker of aging, based on its ability to predict human chronological age.[61] Basic blood biochemistry and cell counts can also be used to accurately predict the chronological age.[62] It is also possible to predict the human chronological age using the transcriptomic aging clocks.[63]

There is research and development of further biomarkers, detection systems and software systems to measure biological age of different tissues or systems or overall. For example, a deep learning (DL) software using anatomic magnetic resonance images estimated brain age with relatively high accuracy, including detecting early signs of Alzheimer's disease and varying neuroanatomical patterns of neurological aging,[64] and a DL tool was reported as to calculate a person's inflammatory age based on patterns of systemic age-related inflammation.[65]

Aging clocks have been used to evaluate impacts of interventions on humans, including combination therapies.[66][additional citation(s) needed]

Genetic determinants of aging edit

Main article: Genetics of aging

A number of genetic components of aging have been identified using model organisms, ranging from the simple budding yeast Saccharomyces cerevisiae to worms such as Caenorhabditis elegans and fruit flies (Drosophila melanogaster). Study of these organisms has revealed the presence of at least two conserved aging pathways.

Gene expression is imperfectly controlled, and it is possible that random fluctuations in the expression levels of many genes contribute to the aging process as suggested by a study of such genes in yeast.[67] Individual cells, which are genetically identical, nonetheless can have substantially different responses to outside stimuli, and markedly different lifespans, indicating the epigenetic factors play an important role in gene expression and aging as well as genetic factors. There is research into epigenetics of aging.

The ability to repair DNA double-strand breaks declines with aging in mice[68] and humans.[69]

A set of rare hereditary (genetics) disorders, each called progeria, has been known for some time. Sufferers exhibit symptoms resembling accelerated aging, including wrinkled skin. The cause of Hutchinson–Gilford progeria syndrome was reported in the journal Nature in May 2003.[70] This report suggests that DNA damage, not oxidative stress, is the cause of this form of accelerated aging.

A study indicates that aging may shift activity toward short genes or shorter transcript length and that this can be countered by interventions.[71]

Healthspans and aging in society edit

 
Past and projected age of the human world population through time as of 2021[72]
 
Healthspan-lifespan gap (LHG)[72]
 
Healthspan extension relies on the unison of social, clinical and scientific programs or domains of work.[72]

Healthspan can broadly be defined as the period of one's life that one is healthy, such as free of significant diseases[73] or declines of capacities (e.g. of senses, muscle, endurance and cognition).

These paragraphs are an excerpt from Global health § Multimorbidity, age-related diseases and aging.[edit]
With aging populations, there is a rise of age-related diseases which puts major burdens on healthcare systems as well as contemporary economies or contemporary economics and their appendant societal systems. Healthspan extension and anti-aging research seek to extend the span of health in the old as well as slow aging or its negative impacts such as physical and mental decline. Modern anti-senescent and regenerative technology with augmented decision making could help "responsibly bridge the healthspan-lifespan gap for a future of equitable global wellbeing".[74] Aging is "the most prevalent risk factor for chronic disease, frailty and disability, and it is estimated that there will be over 2 billion persons age > 60 by the year 2050", making it a large global health challenge that demands substantial (and well-orchestrated or efficient) efforts, including interventions that alter and target the inborn aging process.[75]

Biological aging or the LHG comes with a great cost burden to society, including potentially rising health care costs (also depending on types and costs of treatments).[72][76] This, along with global quality of life or wellbeing, highlight the importance of extending healthspans.[72]

Many measures that may extend lifespans may simultaneously also extend healthspans, albeit that is not necessarily the case, indicating that "lifespan can no longer be the sole parameter of interest" in related research.[77] While recent life expectancy increases were not followed by "parallel" healthspan expansion,[72] awareness of the concept and issues of healthspan lags as of 2017.[73] Scientists have noted that "[c]hronic diseases of aging are increasing and are inflicting untold costs on human quality of life".[76]

Interventions edit

This section is an excerpt from Life extension.[edit]

Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled limit of 125 years.[78] Several researchers in the area, along with "life extensionists", "immortalists", or "longevists" (those who wish to achieve longer lives themselves), postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement (such as with artificial organs or xenotransplantations) will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition (agerasia[79]). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.

The sale of purported anti-aging products such as supplements and hormone replacement is a lucrative global industry. For example, the industry that promotes the use of hormones as a treatment for consumers to slow or reverse the aging process in the US market generated about $50 billion of revenue a year in 2009.[80] The use of such hormone products has not been proven to be effective or safe.[80][81][82][83]

See also edit

References edit

  1. ^ a b Kirkwood, T. B. L. (1977). "Evolution of ageing". Nature. 270 (5635): 301–304. Bibcode:1977Natur.270..301K. doi:10.1038/270301a0. ISSN 0028-0836. PMID 593350. S2CID 492012. from the original on 15 November 2023. Retrieved 31 January 2022.
  2. ^ a b Nelson P, Masel J (December 2017). "Intercellular competition and the inevitability of multicellular aging". Proceedings of the National Academy of Sciences of the United States of America. 114 (49): 12982–12987. Bibcode:2017PNAS..11412982N. doi:10.1073/pnas.1618854114. PMC 5724245. PMID 29087299.
  3. ^ "Aging and Gerontology Glossary". from the original on 19 October 2019. Retrieved 26 February 2011.
  4. ^ López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (June 2013). "The hallmarks of aging". Cell. 153 (6): 1194–217. doi:10.1016/j.cell.2013.05.039. PMC 3836174. PMID 23746838.
  5. ^ López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido (19 January 2023). "Hallmarks of aging: An expanding universe". Cell. 186 (2): 243–278. doi:10.1016/j.cell.2022.11.001. ISSN 0092-8674. PMID 36599349. S2CID 255394876. from the original on 17 February 2023. Retrieved 17 February 2023.
  6. ^ a b Holmes GE, Bernstein C, Bernstein H (September 1992). "Oxidative and other DNA damages as the basis of aging: a review". Mutat. Res. 275 (3–6): 305–15. doi:10.1016/0921-8734(92)90034-m. PMID 1383772.
  7. ^ a b Williams GC (1957). "Pleiotropy, natural selection, and the evolution of senescence". Evolution. 11 (4): 398–411. doi:10.2307/2406060. JSTOR 2406060.
  8. ^ Austad SN (February 2009). "Comparative biology of aging". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 64 (2): 199–201. doi:10.1093/gerona/gln060. PMC 2655036. PMID 19223603.
  9. ^ Wang L, Cui J, Jin B, Zhao J, Xu H, Lu Z, et al. (January 2020). "Multifeature analyses of vascular cambial cells reveal longevity mechanisms in old Ginkgo biloba trees". Proceedings of the National Academy of Sciences of the United States of America. 117 (4): 2201–2210. Bibcode:2020PNAS..117.2201W. doi:10.1073/pnas.1916548117. PMC 6995005. PMID 31932448.
  10. ^ Ackermann M, Stearns SC, Jenal U (June 2003). "Senescence in a bacterium with asymmetric division". Science. 300 (5627): 1920. doi:10.1126/science.1083532. PMID 12817142. S2CID 34770745.
  11. ^ Stewart EJ, Madden R, Paul G, Taddei F (February 2005). "Aging and death in an organism that reproduces by morphologically symmetric division". PLOS Biology. 3 (2): e45. doi:10.1371/journal.pbio.0030045. PMC 546039. PMID 15685293.
  12. ^ Dańko MJ, Kozłowski J, Schaible R (October 2015). "Unraveling the non-senescence phenomenon in Hydra". Journal of Theoretical Biology. 382: 137–49. Bibcode:2015JThBi.382..137D. doi:10.1016/j.jtbi.2015.06.043. PMID 26163368.
  13. ^ Tan TC, Rahman R, Jaber-Hijazi F, Felix DA, Chen C, Louis EJ, Aboobaker A (March 2012). "Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms". Proceedings of the National Academy of Sciences of the United States of America. 109 (11): 4209–14. Bibcode:2012PNAS..109.4209T. doi:10.1073/pnas.1118885109. PMC 3306686. PMID 22371573.
  14. ^ Lisenkova AA, Grigorenko AP, Tyazhelova TV, Andreeva TV, Gusev FE, Manakhov AD, et al. (February 2017). "Complete mitochondrial genome and evolutionary analysis of Turritopsis dohrnii, the "immortal" jellyfish with a reversible life-cycle". Molecular Phylogenetics and Evolution. 107: 232–238. doi:10.1016/j.ympev.2016.11.007. PMID 27845203.
  15. ^ Piraino S, Boero F, Aeschbach B, Schmid V (June 1996). "Reversing the Life Cycle: Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula (Cnidaria, Hydrozoa)". The Biological Bulletin. 190 (3): 302–312. doi:10.2307/1543022. JSTOR 1543022. PMID 29227703.
  16. ^ Vaupel JW, Baudisch A, Dölling M, Roach DA, Gampe J (June 2004). "The case for negative senescence". Theoretical Population Biology. 65 (4): 339–51. doi:10.1016/j.tpb.2003.12.003. PMID 15136009.
  17. ^ Viña J, Borrás C, Miquel J (2007). "Theories of ageing". IUBMB Life. 59 (4–5): 249–54. doi:10.1080/15216540601178067. PMID 17505961.
  18. ^ Kirkwood, Thomas B. L.; Austad, Steven N. (2000). "Why do we age?". Nature. 408 (6809): 233–238. Bibcode:2000Natur.408..233K. doi:10.1038/35041682. ISSN 0028-0836. PMID 11089980. S2CID 2579770. from the original on 15 November 2023. Retrieved 31 January 2022.
  19. ^ Medawar, Peter Brian, Sir (1952). An unsolved problem of biology. Published for the College by H. K. Lewis & Co. Ltd. OCLC 869293719. from the original on 15 November 2023. Retrieved 31 January 2022.{{cite book}}: CS1 maint: multiple names: authors list (link)
  20. ^ Rose, Michael R. (1991). Evolutionary biology of aging. Oxford University Press. ISBN 1-4237-6520-6. OCLC 228167629. from the original on 15 November 2023. Retrieved 31 January 2022.
  21. ^ Kirkwood, Tom (2006). Time of Our Lives : the Science of Human Aging. Oxford University Press. ISBN 978-0-19-802939-7. OCLC 437175125. from the original on 15 November 2023. Retrieved 31 January 2022.
  22. ^ Hammers M, Richardson DS, Burke T, Komdeur J (September 2013). "The impact of reproductive investment and early-life environmental conditions on senescence: support for the disposable soma hypothesis". Journal of Evolutionary Biology. 26 (9): 1999–2007. doi:10.1111/jeb.12204. hdl:11370/9cc6749c-f67d-40ab-a253-a06650c32102. PMID 23961923. S2CID 46466320.
  23. ^ Kirkwood TB, Rose MR (April 1991). "Evolution of senescence: late survival sacrificed for reproduction". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 332 (1262): 15–24. Bibcode:1991RSPTB.332...15K. doi:10.1098/rstb.1991.0028. PMID 1677205.
  24. ^ Atwood CS, Bowen RL (2011). "The reproductive-cell cycle theory of aging: an update". Experimental Gerontology. 46 (2–3): 100–7. doi:10.1016/j.exger.2010.09.007. PMID 20851172. S2CID 20998909.
  25. ^ Harman D (July 1956). "Aging: a theory based on free radical and radiation chemistry". Journal of Gerontology. 11 (3): 298–300. doi:10.1093/geronj/11.3.298. hdl:2027/mdp.39015086547422. PMID 13332224.
  26. ^ Stadtman ER (August 1992). "Protein oxidation and aging". Science. 257 (5074): 1220–4. Bibcode:1992Sci...257.1220S. doi:10.1126/science.1355616. PMID 1355616. from the original on 31 July 2021. Retrieved 21 July 2021.
  27. ^ Sohal RS, Agarwal S, Dubey A, Orr WC (August 1993). "Protein oxidative damage is associated with life expectancy of houseflies". Proceedings of the National Academy of Sciences of the United States of America. 90 (15): 7255–9. Bibcode:1993PNAS...90.7255S. doi:10.1073/pnas.90.15.7255. PMC 47115. PMID 8346242.
  28. ^ Pearl R (1928). The Rate of Living, Being an Account of Some Experimental Studies on the Biology of Life Duration. New York: Alfred A. Knopf.[page needed]
  29. ^ Brunet-Rossinni AK, Austad SN (2004). "Ageing studies on bats: a review". Biogerontology. 5 (4): 211–22. doi:10.1023/B:BGEN.0000038022.65024.d8. PMID 15314271. S2CID 22755811.
  30. ^ de Magalhães JP, Costa J, Church GM (February 2007). "An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 62 (2): 149–60. CiteSeerX 10.1.1.596.2815. doi:10.1093/gerona/62.2.149. PMC 2288695. PMID 17339640.
  31. ^ Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R (May 2012). "Association of coffee drinking with total and cause-specific mortality". The New England Journal of Medicine. 366 (20): 1891–904. doi:10.1056/NEJMoa1112010. PMC 3439152. PMID 22591295.
  32. ^ Yang Y, Chan SW, Hu M, Walden R, Tomlinson B (2011). "Effects of some common food constituents on cardiovascular disease". ISRN Cardiology. 2011: 397136. doi:10.5402/2011/397136. PMC 3262529. PMID 22347642.
  33. ^ Poole, Robin; Kennedy, Oliver J.; Roderick, Paul; Fallowfield, Jonathan A.; Hayes, Peter C.; Parkes, Julie (22 November 2017). "Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes". BMJ. 359: j5024. doi:10.1136/bmj.j5024. ISSN 0959-8138. PMC 5696634. PMID 29167102.
  34. ^ O'Keefe, James H.; DiNicolantonio, James J.; Lavie, Carl J. (1 May 2018). "Coffee for Cardioprotection and Longevity". Progress in Cardiovascular Diseases. 61 (1): 38–42. doi:10.1016/j.pcad.2018.02.002. ISSN 0033-0620. PMID 29474816.
  35. ^ Grosso, Giuseppe; Godos, Justyna; Galvano, Fabio; Giovannucci, Edward L. (21 August 2017). "Coffee, Caffeine, and Health Outcomes: An Umbrella Review". Annual Review of Nutrition. 37 (1): 131–156. doi:10.1146/annurev-nutr-071816-064941. ISSN 0199-9885. PMID 28826374.
  36. ^ Dirks-Naylor, Amie J. (15 December 2015). "The benefits of coffee on skeletal muscle". Life Sciences. 143: 182–186. doi:10.1016/j.lfs.2015.11.005. ISSN 0024-3205. PMID 26546720.
  37. ^ Reis, Caio E. G.; Dórea, José G.; da Costa, Teresa H. M. (1 July 2019). "Effects of coffee consumption on glucose metabolism: A systematic review of clinical trials". Journal of Traditional and Complementary Medicine. 9 (3): 184–191. doi:10.1016/j.jtcme.2018.01.001. ISSN 2225-4110. PMC 6544578. PMID 31193893.
  38. ^ Loureiro, Laís Monteiro Rodrigues; Reis, Caio Eduardo Gonçalves; Costa, Teresa Helena Macedo da (1 May 2018). "Effects of Coffee Components on Muscle Glycogen Recovery: A Systematic Review". International Journal of Sport Nutrition and Exercise Metabolism. 28 (3): 284–293. doi:10.1123/ijsnem.2017-0342. ISSN 1543-2742. PMID 29345166.
  39. ^ Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). "Cancer and aging as consequences of un-repaired DNA damage.". In Kimura H, Suzuki A (eds.). New Research on DNA Damage. Nova Science Publishers. pp. 1–47. ISBN 978-1604565812. from the original on 15 November 2023. Retrieved 4 February 2016.
  40. ^ Pan MR, Li K, Lin SY, Hung WC (May 2016). "Connecting the Dots: From DNA Damage and Repair to Aging". International Journal of Molecular Sciences. 17 (5): 685. doi:10.3390/ijms17050685. PMC 4881511. PMID 27164092.
  41. ^ a b Schumacher, Björn; Pothof, Joris; Vijg, Jan; Hoeijmakers, Jan H. J. (April 2021). "The central role of DNA damage in the ageing process". Nature. 592 (7856): 695–703. doi:10.1038/s41586-021-03307-7. ISSN 1476-4687. PMC 9844150. PMID 33911272.
  42. ^ Gensler, H. L.; Bernstein, H. (September 1981). "DNA damage as the primary cause of aging". The Quarterly Review of Biology. 56 (3): 279–303. doi:10.1086/412317. ISSN 0033-5770. PMID 7031747. S2CID 20822805.
  43. ^ Spencer RL, Hutchison KE (1999). (PDF). Alcohol Research & Health. 23 (4): 272–83. PMC 6760387. PMID 10890824. Archived from the original (PDF) on 11 December 2018. Retrieved 8 April 2008.
  44. ^ Fabian D, Flatt T (2011). "The Evolution of Aging". Scitable. Nature Publishing Group. from the original on 31 March 2019. Retrieved 10 December 2014.
  45. ^ Medawar PB (1946). "Old age and natural death". Modern Quarterly. 1: 30–56.
  46. ^ Medawar PB (1952). An Unsolved Problem of Biology. London: H. K. Lewis & Co. Ltd.[page needed]
  47. ^ Liu, Xiaoqian; Liu, Zunpeng; Wu, Zeming; Ren, Jie; Fan, Yanling; Sun, Liang; Cao, Gang; Niu, Yuyu; Zhang, Baohu; Ji, Qianzhao; Jiang, Xiaoyu; Wang, Cui; Wang, Qiaoran; Ji, Zhejun; Li, Lanzhu; Esteban, Concepcion Rodriguez; Yan, Kaowen; Li, Wei; Cai, Yusheng; Wang, Si; Zheng, Aihua; Zhang, Yong E.; Tan, Shengjun; Cai, Yingao; Song, Moshi; Lu, Falong; Tang, Fuchou; Ji, Weizhi; Zhou, Qi; Belmonte, Juan Carlos Izpisua; Zhang, Weiqi; Qu, Jing; Liu, Guang-Hui (19 January 2023). "Resurrection of endogenous retroviruses during aging reinforces senescence". Cell. 186 (2): 287–304.e26. doi:10.1016/j.cell.2022.12.017. ISSN 0092-8674. PMID 36610399. S2CID 232060038.
    • Expert explanation of the study: "Aging and Retroviruses". Science. from the original on 17 February 2023. Retrieved 17 February 2023.
  48. ^ Smith J., A., Daniel R. "Stem Cells and Aging: A Chicken-Or-Egg Issue?". Aging and Disease. 2012 Jun, Vol. 3, Number 3; 260–268.
  49. ^ Mahla RS (2016). "Stem cells application in regenerative medicine and disease threpeutics". International Journal of Cell Biology. 2016 (7): 19. doi:10.1155/2016/6940283. PMC 4969512. PMID 27516776.
  50. ^ Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL (2007). "Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age". Nature. 447 (7145): 725–9. Bibcode:2007Natur.447..725R. doi:10.1038/nature05862. PMID 17554309. S2CID 4416445.
  51. ^ a b Beerman I, Seita J, Inlay MA, Weissman IL, Rossi DJ (2014). "Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle". Cell Stem Cell. 15 (1): 37–50. doi:10.1016/j.stem.2014.04.016. PMC 4082747. PMID 24813857.
  52. ^ a b Nijnik A, Woodbine L, Marchetti C, Dawson S, Lambe T, Liu C, Rodrigues NP, Crockford TL, Cabuy E, Vindigni A, Enver T, Bell JI, Slijepcevic P, Goodnow CC, Jeggo PA, Cornall RJ (2007). "DNA repair is limiting for haematopoietic stem cells during ageing". Nature. 447 (7145): 686–90. Bibcode:2007Natur.447..686N. doi:10.1038/nature05875. PMID 17554302. S2CID 4332976.
  53. ^ "Research may reveal why people can suddenly become frail in their 70s". The Guardian. 1 June 2022. Retrieved 18 July 2022.
  54. ^ Mitchell, Emily; Spencer Chapman, Michael; Williams, Nicholas; Dawson, Kevin J.; Mende, Nicole; Calderbank, Emily F.; Jung, Hyunchul; Mitchell, Thomas; Coorens, Tim H. H.; Spencer, David H.; Machado, Heather; Lee-Six, Henry; Davies, Megan; Hayler, Daniel; Fabre, Margarete A.; Mahbubani, Krishnaa; Abascal, Federico; Cagan, Alex; Vassiliou, George S.; Baxter, Joanna; Martincorena, Inigo; Stratton, Michael R.; Kent, David G.; Chatterjee, Krishna; Parsy, Kourosh Saeb; Green, Anthony R.; Nangalia, Jyoti; Laurenti, Elisa; Campbell, Peter J. (June 2022). "Clonal dynamics of haematopoiesis across the human lifespan". Nature. 606 (7913): 343–350. Bibcode:2022Natur.606..343M. doi:10.1038/s41586-022-04786-y. ISSN 1476-4687. PMC 9177428. PMID 35650442.
  55. ^ Kolata, Gina (14 July 2022). "As Y Chromosomes Vanish With Age, Heart Risks May Grow". The New York Times. Retrieved 21 August 2022.
  56. ^ Sano, Soichi; Horitani, Keita; Ogawa, Hayato; Halvardson, Jonatan; Chavkin, Nicholas W.; Wang, Ying; Sano, Miho; Mattisson, Jonas; Hata, Atsushi; Danielsson, Marcus; Miura-Yura, Emiri; Zaghlool, Ammar; Evans, Megan A.; Fall, Tove; De Hoyos, Henry N.; Sundström, Johan; Yura, Yoshimitsu; Kour, Anupreet; Arai, Yohei; Thel, Mark C.; Arai, Yuka; Mychaleckyj, Josyf C.; Hirschi, Karen K.; Forsberg, Lars A.; Walsh, Kenneth (15 July 2022). "Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality". Science. 377 (6603): 292–297. Bibcode:2022Sci...377..292S. doi:10.1126/science.abn3100. ISSN 0036-8075. PMC 9437978. PMID 35857592.
  57. ^ Gasmi A, Chirumbolo S, Peana M, Mujawdiya PK, Dadar M, Menzel A, Bjørklund G (17 September 2020). "Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures". Current Medicinal Chemistry. 28 (8): 1471–1488. doi:10.2174/0929867327999200917150652. PMID 32942969. S2CID 221789280.
  58. ^ Baker GT, Sprott RL (1988). "Biomarkers of aging". Experimental Gerontology. 23 (4–5): 223–39. doi:10.1016/0531-5565(88)90025-3. PMID 3058488. S2CID 31039588. from the original on 24 October 2021. Retrieved 12 July 2019.
  59. ^ Van Neste D, Tobin DJ (2004). "Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging". Micron. 35 (3): 193–200. doi:10.1016/j.micron.2003.11.006. PMID 15036274.
  60. ^ Miller RA (April 2001). "Biomarkers of aging: prediction of longevity by using age-sensitive T-cell subset determinations in a middle-aged, genetically heterogeneous mouse population". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 56 (4): B180-6. doi:10.1093/gerona/56.4.b180. PMC 7537444. PMID 11283189.
  61. ^ Horvath S (2013). "DNA methylation age of human tissues and cell types". Genome Biology. 14 (10): R115. doi:10.1186/gb-2013-14-10-r115. PMC 4015143. PMID 24138928.
  62. ^ Putin E, Mamoshina P, Aliper A, Korzinkin M, Moskalev A, Kolosov A, et al. (May 2016). "Deep biomarkers of human aging: Application of deep neural networks to biomarker development". Aging. 8 (5): 1021–33. doi:10.18632/aging.100968. PMC 4931851. PMID 27191382.
  63. ^ Peters MJ, Joehanes R, Pilling LC, Schurmann C, Conneely KN, Powell J, et al. (October 2015). "The transcriptional landscape of age in human peripheral blood". Nature Communications. 6: 8570. Bibcode:2015NatCo...6.8570.. doi:10.1038/ncomms9570. PMC 4639797. PMID 26490707.
  64. ^ Yin, Chenzhong; Imms, Phoebe; Cheng, Mingxi; et al. (10 January 2023). "Anatomically interpretable deep learning of brain age captures domain-specific cognitive impairment". Proceedings of the National Academy of Sciences. 120 (2): e2214634120. Bibcode:2023PNAS..12014634Y. doi:10.1073/pnas.2214634120. ISSN 0027-8424. PMC 9926270. PMID 36595679.
    • University press release: "How old is your brain, really? AI-powered analysis accurately reflects risk of cognitive decline and Alzheimer's disease". University of Southern California via medicalxpress.com. from the original on 17 February 2023. Retrieved 17 February 2023.
    • News article about the study: "KI kann wahres Alter des Hirns bestimmen". Deutschlandfunk Nova (in German). from the original on 17 February 2023. Retrieved 17 February 2023.
  65. ^ Sayed, Nazish; Huang, Yingxiang; Nguyen, Khiem; Krejciova-Rajaniemi, Zuzana; Grawe, Anissa P.; Gao, Tianxiang; Tibshirani, Robert; Hastie, Trevor; Alpert, Ayelet; Cui, Lu; Kuznetsova, Tatiana; Rosenberg-Hasson, Yael; Ostan, Rita; Monti, Daniela; Lehallier, Benoit; Shen-Orr, Shai S.; Maecker, Holden T.; Dekker, Cornelia L.; Wyss-Coray, Tony; Franceschi, Claudio; Jojic, Vladimir; Haddad, François; Montoya, José G.; Wu, Joseph C.; Davis, Mark M.; Furman, David (July 2021). "An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging". Nature Aging. 1 (7): 598–615. doi:10.1038/s43587-021-00082-y. ISSN 2662-8465. PMC 8654267. PMID 34888528.
    • News article about the study: "Tool that calculates immune system age could predict frailty and disease". New Atlas. 13 July 2021. from the original on 26 July 2021. Retrieved 26 July 2021.
  66. ^ Fitzgerald, K. N.; Hodges, R.; Hanes, D.; Stack, E.; Cheishvili, D.; Szyf, M.; Henkel, J.; Twedt, M. W.; Giannopoulou, D.; Herdell, J.; Logan, S.; Bradley, R. (2021). "Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial". Aging. 13 (7): 9419–9432. doi:10.18632/aging.202913. PMC 8064200. PMID 33844651. from the original on 2 June 2021. Retrieved 28 June 2021.
  67. ^ Ryley J, Pereira-Smith OM (2006). "Microfluidics device for single cell gene expression analysis in Saccharomyces cerevisiae". Yeast. 23 (14–15): 1065–73. doi:10.1002/yea.1412. PMID 17083143. S2CID 31356425.
  68. ^ Vaidya A, Mao Z, Tian X, Spencer B, Seluanov A, Gorbunova V (July 2014). "Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age". PLOS Genet. 10 (7): e1004511. doi:10.1371/journal.pgen.1004511. PMC 4102425. PMID 25033455.
  69. ^ Li Z, Zhang W, Chen Y, Guo W, Zhang J, Tang H, Xu Z, Zhang H, Tao Y, Wang F, Jiang Y, Sun FL, Mao Z (November 2016). "Impaired DNA double-strand break repair contributes to the age-associated rise of genomic instability in humans". Cell Death Differ. 23 (11): 1765–77. doi:10.1038/cdd.2016.65. PMC 5071568. PMID 27391797.
  70. ^ Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL (May 2003). "A progeroid syndrome in mice is caused by defects in A-type lamins". Nature. 423 (6937): 298–301. Bibcode:2003Natur.423..298M. doi:10.1038/nature01631. PMID 12748643. S2CID 4360055. from the original on 30 May 2022. Retrieved 21 July 2021.
  71. ^ Stoeger, Thomas; Grant, Rogan A.; McQuattie-Pimentel, Alexandra C.; Anekalla, Kishore R.; Liu, Sophia S.; Tejedor-Navarro, Heliodoro; Singer, Benjamin D.; Abdala-Valencia, Hiam; Schwake, Michael; Tetreault, Marie-Pier; Perlman, Harris; Balch, William E.; Chandel, Navdeep S.; Ridge, Karen M.; Sznajder, Jacob I.; Morimoto, Richard I.; Misharin, Alexander V.; Budinger, G. R. Scott; Nunes Amaral, Luis A. (December 2022). "Aging is associated with a systemic length-associated transcriptome imbalance". Nature Aging. 2 (12): 1191–1206. doi:10.1038/s43587-022-00317-6. ISSN 2662-8465. PMC 10154227. PMID 37118543.
    • University press release: "Aging is driven by unbalanced genes, finds AI analysis of multiple species". Northwestern University via phys.org. from the original on 2 February 2023. Retrieved 18 January 2023.
    • News article about the study: Kwon, Diana. "Aging Is Linked to More Activity in Short Genes Than in Long Genes". Scientific American. from the original on 17 January 2023. Retrieved 18 January 2023.
  72. ^ a b c d e f Garmany, Armin; Yamada, Satsuki; Terzic, Andre (23 September 2021). "Longevity leap: mind the healthspan gap". npj Regenerative Medicine. 6 (1): 57. doi:10.1038/s41536-021-00169-5. ISSN 2057-3995. PMC 8460831. PMID 34556664.
    • Non-profit hospital press release: Buckles, Susan. "A regenerative reset for aging » Center for Regenerative Biotherapeutics". Mayo Clinic. from the original on 1 March 2023. Retrieved 1 March 2023.
  73. ^ a b "Healthspan is more important than lifespan, so why don't more people know about it? | Institute for Public Health | Washington University in St. Louis". publichealth.wustl.edu. from the original on 1 March 2023. Retrieved 1 March 2023.
  74. ^ Garmany A, Yamada S, Terzic A (September 2021). "Longevity leap: mind the healthspan gap". npj Regenerative Medicine. 6 (1): 57. doi:10.1038/s41536-021-00169-5. PMC 8460831. PMID 34556664.
  75. ^ Farrelly C (November 2022). "Aging, Equality and the Human Healthspan". HEC Forum: 1–19. doi:10.1007/s10730-022-09499-3. PMC 9644010. PMID 36348214.
  76. ^ a b Hansen, Malene; Kennedy, Brian K. (1 August 2016). "Does Longer Lifespan Mean Longer Healthspan?". Trends in Cell Biology. 26 (8): 565–568. doi:10.1016/j.tcb.2016.05.002. ISSN 0962-8924. PMC 4969078. PMID 27238421.
  77. ^ Bansal, Ankita; Zhu, Lihua J.; Yen, Kelvin; Tissenbaum, Heidi A. (20 January 2015). "Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants". Proceedings of the National Academy of Sciences. 112 (3): E277-86. Bibcode:2015PNAS..112E.277B. doi:10.1073/pnas.1412192112. ISSN 0027-8424. PMC 4311797. PMID 25561524.
  78. ^ Turner BS (2009). Can We Live Forever? A Sociological and Moral Inquiry. Anthem Press. p. 3.
  79. ^ "agerasia". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
  80. ^ a b Japsen B (15 June 2009). "AMA report questions science behind using hormones as anti-aging treatment". The Chicago Tribune. Retrieved 17 July 2009.
  81. ^ Holliday R (April 2009). "The extreme arrogance of anti-aging medicine". Biogerontology. 10 (2): 223–228. doi:10.1007/s10522-008-9170-6. PMID 18726707. S2CID 764136.
  82. ^ Olshansky SJ, Hayflick L, Carnes BA (August 2002). "Position statement on human aging". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 57 (8): B292–B297. CiteSeerX 10.1.1.541.3004. doi:10.1093/gerona/57.8.B292. PMID 12145354.
  83. ^ Warner H, Anderson J, Austad S, Bergamini E, Bredesen D, Butler R, et al. (November 2005). "Science fact and the SENS agenda. What can we reasonably expect from ageing research?". EMBO Reports. 6 (11): 1006–1008. doi:10.1038/sj.embor.7400555. PMC 1371037. PMID 16264422.

External links edit

 
Look up senescence in Wiktionary, the free dictionary.
 
Wikimedia Commons has media related to Senescence.

January 09, 2024
senescence, this, article, about, aging, whole, organisms, including, animals, aging, specifically, humans, aging, plants, plant, senescence, cells, that, stop, dividing, cellular, senescence, bacteria, bacterial, senescence, biological, aging, gradual, deteri. This article is about the aging of whole organisms including animals For aging specifically in humans see Aging For plants see Plant senescence For cells that stop dividing see Cellular senescence For bacteria see Bacterial senescence Senescence s ɪ ˈ n ɛ s e n s 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 later part of an organism s life cycle 1 2 However the resulting effects of senescence can be delayed The 1934 discovery that calorie restriction can extend lifespans by 50 in rats the existence of species having negligible senescence and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age related diseases Rare human mutations can cause accelerated aging diseases Supercentenarian Ann Pouder 8 April 1807 10 July 1917 photographed on her 110th birthday A heavily lined face is common in human senescence Environmental factors may affect aging for example overexposure to ultraviolet radiation accelerates skin aging Different parts of the body may age at different rates and distinctly including the brain the cardiovascular system and muscle Similarly functions may distinctly decline with aging including movement control and memory Two organisms of the same species can also age at different rates making biological aging and chronological aging distinct concepts Contents 1 Definition and characteristics 2 Variation among species 3 Theories of aging 3 1 Evolutionary aging theories 3 1 1 Antagonistic pleiotropy 3 1 2 Cancer versus cellular senescence tradeoff theory of aging 3 1 3 Disposable soma 3 2 Programmed aging theories 3 3 Damage accumulation theories 3 3 1 The free radical theory of aging 3 3 2 Chemical damage 3 3 3 Mutation accumulation 3 3 4 Other damage 3 4 Stem cell theories of aging 4 Biomarkers of aging 4 1 Aging clocks 5 Genetic determinants of aging 6 Healthspans and aging in society 7 Interventions 8 See also 9 References 10 External linksDefinition and characteristics editOrganismal senescence is the aging of whole organisms Actuarial senescence can be defined as an increase in mortality and or a decrease in fecundity with age The Gompertz Makeham law of mortality says that the age dependent component of the mortality rate increases exponentially with age Aging is characterized by the declining ability to respond to stress increased homeostatic imbalance and increased risk of aging associated diseases including cancer and heart disease Aging has been defined as a progressive deterioration of physiological function an intrinsic age related process of loss of viability and increase in vulnerability 3 In 2013 a group of scientists defined nine hallmarks of aging that are common between organisms with emphasis on mammals genomic instability telomere attrition epigenetic alterations loss of proteostasis deregulated nutrient sensing mitochondrial dysfunction cellular senescence stem cell exhaustion altered intercellular communication 4 In a decadal update three hallmarks have been added totaling 12 proposed hallmarks disabled macroautophagy chronic inflammation dysbiosis 5 The environment induces damage at various levels e g damage to DNA and damage to tissues and cells by oxygen radicals widely known as free radicals and some of this damage is not repaired and thus accumulates with time 6 Cloning from somatic cells rather than germ cells may begin life with a higher initial load of damage Dolly the sheep died young from a contagious lung disease but data on an entire population of cloned individuals would be necessary to measure mortality rates and quantify aging citation needed The evolutionary theorist George Williams wrote It is remarkable that after a seemingly miraculous feat of morphogenesis a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed 7 Variation among species editFurther information Longevity Non human biological longevity Different speeds with which mortality increases with age correspond to different maximum life span among species For example a mouse is elderly at 3 years a human is elderly at 80 years 8 and ginkgo trees show little effect of age even at 667 years 9 Almost all organisms senesce including bacteria which have asymmetries between mother and daughter cells upon cell division with the mother cell experiencing aging while the daughter is rejuvenated 10 11 There is negligible senescence in some groups such as the genus Hydra 12 Planarian flatworms have apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult stem cells 13 These planarians are not biologically immortal but rather their death rate slowly increases with age Organisms that are thought to be biologically immortal would in one instance be Turritopsis dohrnii also known as the immortal jellyfish due to its ability to revert to its youth when it undergoes stress during adulthood 14 The reproductive system is observed to remain intact and even the gonads of Turritopsis dohrnii are existing 15 Some species exhibit negative senescence in which reproduction capability increases or is stable and mortality falls with age resulting from the advantages of increased body size during aging 16 Theories of aging editThis section needs expansion You can help by adding to it March 2023 More than 300 different theories have been posited to explain the nature mechanisms and causes reasons for natural emergence or factors of aging 17 additional citation s needed Good theories would both explain past observations and predict the results of future experiments Some of the theories may complement each other overlap contradict or may not preclude various other theories citation needed Theories of aging fall into two broad categories evolutionary theories of aging and mechanistic theories of aging Evolutionary theories of aging primarily explain why aging happens 18 but do not concern themselves with the molecular mechanism s that drive the process All evolutionary theories of aging rest on the basic mechanisms that the force of natural selection declines with age 19 20 Mechanistic theories of aging can be divided into theories that propose aging is programmed and damage accumulation theories i e those that propose aging to be caused by specific molecular changes occurring over time This section is an excerpt from Stem cell theory of aging Other theories of aging edit The aging process can be explained with different theories These are evolutionary theories molecular theories system theories and cellular theories The evolutionary theory of ageing was first proposed in the late 1940s and can be explained briefly by the accumulation of mutations evolution of ageing disposable soma and antagonistic pleiotropy hypothesis The molecular theories of ageing include phenomena such as gene regulation gene expression codon restriction error catastrophe somatic mutation accumulation of genetic material DNA damage DNA damage theory of aging and dysdifferentiation The system theories include the immunologic approach to ageing rate of living and the alterations in neuroendocrinal control mechanisms See homeostasis Cellular theory of ageing can be categorized as telomere theory free radical theory free radical theory of aging and apoptosis The stem cell theory of aging is also a sub category of cellular theories Evolutionary aging theories edit Main article Evolution of ageing Antagonistic pleiotropy edit Main article Antagonistic pleiotropy hypothesis One theory was proposed by George C Williams 7 and involves antagonistic pleiotropy A single gene may affect multiple traits Some traits that increase fitness early in life may also have negative effects later in life But because many more individuals are alive at young ages than at old ages even small positive effects early can be strongly selected for and large negative effects later may be very weakly selected against Williams suggested the following example Perhaps a gene codes for calcium deposition in bones which promotes juvenile survival and will therefore be favored by natural selection however this same gene promotes calcium deposition in the arteries causing negative atherosclerotic effects in old age Thus harmful biological changes in old age may result from selection for pleiotropic genes that are beneficial early in life but harmful later on In this case selection pressure is relatively high when Fisher s reproductive value is high and relatively low when Fisher s reproductive value is low Cancer versus cellular senescence tradeoff theory of aging edit Main article Immunosenescence Senescent cells within a multicellular organism can be purged by competition between cells but this increases the risk of cancer This leads to an inescapable dilemma between two possibilities the accumulation of physiologically useless senescent cells and cancer both of which lead to increasing rates of mortality with age 2 Disposable soma edit Main article Disposable soma theory of aging The disposable soma theory of aging was proposed by Thomas Kirkwood in 1977 1 21 The theory suggests that aging occurs due to a strategy in which an individual only invests in maintenance of the soma for as long as it has a realistic chance of survival 22 A species that uses resources more efficiently will live longer and therefore be able to pass on genetic information to the next generation The demands of reproduction are high so less effort is invested in repair and maintenance of somatic cells compared to germline cells in order to focus on reproduction and species survival 23 Programmed aging theories edit Programmed theories of aging posit that aging is adaptive normally invoking selection for evolvability or group selection The reproductive cell cycle theory suggests that aging is regulated by changes in hormonal signaling over the lifespan 24 Damage accumulation theories edit The free radical theory of aging edit Main article Free radical theory of aging One of the most prominent theories of aging was first proposed by Harman in 1956 25 It posits that free radicals produced by dissolved oxygen radiation cellular respiration and other sources cause damage to the molecular machines in the cell and gradually wear them down This is also known as oxidative stress There is substantial evidence to back up this theory Old animals have larger amounts of oxidized proteins DNA and lipids than their younger counterparts 26 27 Chemical damage edit This section may be too long to read and navigate comfortably Please consider splitting content into sub articles condensing it or adding subheadings Please discuss this issue on the article s talk page March 2023 nbsp Elderly Klamath woman photographed by Edward S Curtis in 1924See also DNA damage theory of aging One of the earliest aging theories was the Rate of Living Hypothesis described by Raymond Pearl in 1928 28 based on earlier work by Max Rubner which states that fast basal metabolic rate corresponds to short maximum life span While there may be some validity to the idea that for various types of specific damage detailed below that are by products of metabolism all other things being equal a fast metabolism may reduce lifespan in general this theory does not adequately explain the differences in lifespan either within or between species Calorically restricted animals process as much or more calories per gram of body mass as their ad libitum fed counterparts yet exhibit substantially longer lifespans citation needed Similarly metabolic rate is a poor predictor of lifespan for birds bats and other species that it is presumed have reduced mortality from predation and therefore have evolved long lifespans even in the presence of very high metabolic rates 29 In a 2007 analysis it was shown that when modern statistical methods for correcting for the effects of body size and phylogeny are employed metabolic rate does not correlate with longevity in mammals or birds 30 With respect to specific types of chemical damage caused by metabolism it is suggested that damage to long lived biopolymers such as structural proteins or DNA caused by ubiquitous chemical agents in the body such as oxygen and sugars are in part responsible for aging The damage can include breakage of biopolymer chains cross linking of biopolymers or chemical attachment of unnatural substituents haptens to biopolymers citation needed Under normal aerobic conditions approximately 4 of the oxygen metabolized by mitochondria is converted to superoxide ion which can subsequently be converted to hydrogen peroxide hydroxyl radical and eventually other reactive species including other peroxides and singlet oxygen which can in turn generate free radicals capable of damaging structural proteins and DNA 6 Certain metal ions found in the body such as copper and iron may participate in the process In Wilson s disease a hereditary defect that causes the body to retain copper some of the symptoms resemble accelerated senescence These processes termed oxidative stress are linked to the potential benefits of dietary polyphenol antioxidants for example in coffee 31 and tea 32 However their typically positive effects on lifespans when consumption is moderate 33 34 35 have also been explained by effects on autophagy 36 glucose metabolism 37 and AMPK 38 Sugars such as glucose and fructose can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts in a process called glycation These adducts can further rearrange to form reactive species which can then cross link the structural proteins or DNA to similar biopolymers or other biomolecules such as non structural proteins People with diabetes who have elevated blood sugar develop senescence associated disorders much earlier than the general population but can delay such disorders by rigorous control of their blood sugar levels There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation Free radicals can damage proteins lipids or DNA Glycation mainly damages proteins Damaged proteins and lipids accumulate in lysosomes as lipofuscin Chemical damage to structural proteins can lead to loss of function for example damage to collagen of blood vessel walls can lead to vessel wall stiffness and thus hypertension and vessel wall thickening and reactive tissue formation atherosclerosis similar processes in the kidney can lead to kidney failure Damage to enzymes reduces cellular functionality Lipid peroxidation of the inner mitochondrial membrane reduces the electric potential and the ability to generate energy It is probably no accident that nearly all of the so called accelerated aging diseases are due to defective DNA repair enzymes 39 40 DNA damage was proposed in a 2021 review to be the underlying cause of aging because of the mechanistic link of DNA damage to nearly every aspect of the aging phenotype 41 DNA damage induced epigenetic alterations such as DNA methylation and many histone modifications appear to be of particular importance to the aging process 41 Evidence for the theory that DNA damage is the fundamental cause of aging was first reviewed in 1981 42 It is believed that the impact of alcohol on aging can be partly explained by alcohol s activation of the HPA axis which stimulates glucocorticoid secretion long term exposure to which produces symptoms of aging 43 Mutation accumulation edit Main article Mutation accumulation theory Natural selection can support lethal and harmful alleles if their effects are felt after reproduction The geneticist J B S Haldane wondered why the dominant mutation that causes Huntington s disease remained in the population and why natural selection had not eliminated it The onset of this neurological disease is on average at age 45 and is invariably fatal within 10 20 years Haldane assumed that in human prehistory few survived until age 45 Since few were alive at older ages and their contribution to the next generation was therefore small relative to the large cohorts of younger age groups the force of selection against such late acting deleterious mutations was correspondingly small Therefore a genetic load of late acting deleterious mutations could be substantial at mutation selection balance This concept came to be known as the selection shadow 44 Peter Medawar formalised this observation in his mutation accumulation theory of aging 45 46 The force of natural selection weakens with increasing age even in a theoretically immortal population provided only that it is exposed to real hazards of mortality If a genetic disaster happens late enough in individual life its consequences may be completely unimportant Age independent hazards such as predation disease and accidents called extrinsic mortality mean that even a population with negligible senescence will have fewer individuals alive in older age groups Other damage edit A study concluded that retroviruses in the human genomes can become awakened from dormant states and contribute to aging which can be blocked by neutralizing antibodies alleviating cellular senescence and tissue degeneration and to some extent organismal aging 47 Stem cell theories of aging edit This section is an excerpt from Stem cell theory of aging edit The stem cell theory of aging postulates that the aging process is the result of the inability of various types of stem cells to continue to replenish the tissues of an organism with functional differentiated cells capable of maintaining that tissue s or organ s original function Damage and error accumulation in genetic material is always a problem for systems regardless of the age The number of stem cells in young people is very much higher than older people and thus creates a better and more efficient replacement mechanism in the young contrary to the old In other words aging is not a matter of the increase in damage but a matter of failure to replace it due to a decreased number of stem cells Stem cells decrease in number and tend to lose the ability to differentiate into progenies or lymphoid lineages and myeloid lineages Maintaining the dynamic balance of stem cell pools requires several conditions Balancing proliferation and quiescence along with homing See niche and self renewal of hematopoietic stem cells are favoring elements of stem cell pool maintenance while differentiation mobilization and senescence are detrimental elements These detrimental effects will eventually cause apoptosis There are also several challenges when it comes to therapeutic use of stem cells and their ability to replenish organs and tissues First different cells may have different lifespans even though they originate from the same stem cells See T cells and erythrocytes meaning that aging can occur differently in cells that have longer lifespans as opposed to the ones with shorter lifespans Also continual effort to replace the somatic cells may cause exhaustion of stem cells 48 Hematopoietic stem cell agingHematopoietic stem cells HSCs regenerate the blood system throughout life and maintain homeostasis 49 DNA strand breaks accumulate in long term HSCs during aging 50 51 This accumulation is associated with a broad attenuation of DNA repair and response pathways that depends on HSC quiescence 51 DNA ligase 4 Lig4 has a highly specific role in the repair of double strand breaks by non homologous end joining NHEJ Lig4 deficiency in the mouse causes a progressive loss of HSCs during aging 52 These findings suggest that NHEJ is a key determinant of the ability of HSCs to maintain themselves over time 52 Hematopoietic stem cell diversity agingA study showed that the clonal diversity of stem cells that produce blood cells gets drastically reduced around age 70 to a faster growing few substantiating a novel theory of ageing which could enable healthy aging 53 54 Hematopoietic mosaic loss of chromosome YA 2022 study showed that blood cells loss of the Y chromosome in a subset of cells called mosaic loss of chromosome Y mLOY and reportedly affecting at least 40 of 70 years old men to some degree contributes to fibrosis heart risks and mortality in a causal way 55 56 Biomarkers of aging editMain article Biomarkers of aging If different individuals age at different rates then fecundity mortality and functional capacity might be better predicted by biomarkers than by chronological age 57 58 However graying of hair 59 face aging skin wrinkles and other common changes seen with aging are not better indicators of future functionality than chronological age Biogerontologists have continued efforts to find and validate biomarkers of aging but success thus far has been limited Levels of CD4 and CD8 memory T cells and naive T cells have been used to give good predictions of the expected lifespan of middle aged mice 60 Aging clocks edit This section needs expansion You can help by adding to it March 2023 There is interest in an epigenetic clock as a biomarker of aging based on its ability to predict human chronological age 61 Basic blood biochemistry and cell counts can also be used to accurately predict the chronological age 62 It is also possible to predict the human chronological age using the transcriptomic aging clocks 63 There is research and development of further biomarkers detection systems and software systems to measure biological age of different tissues or systems or overall For example a deep learning DL software using anatomic magnetic resonance images estimated brain age with relatively high accuracy including detecting early signs of Alzheimer s disease and varying neuroanatomical patterns of neurological aging 64 and a DL tool was reported as to calculate a person s inflammatory age based on patterns of systemic age related inflammation 65 Aging clocks have been used to evaluate impacts of interventions on humans including combination therapies 66 additional citation s needed Genetic determinants of aging editMain article Genetics of aging A number of genetic components of aging have been identified using model organisms ranging from the simple budding yeast Saccharomyces cerevisiae to worms such as Caenorhabditis elegans and fruit flies Drosophila melanogaster Study of these organisms has revealed the presence of at least two conserved aging pathways Gene expression is imperfectly controlled and it is possible that random fluctuations in the expression levels of many genes contribute to the aging process as suggested by a study of such genes in yeast 67 Individual cells which are genetically identical nonetheless can have substantially different responses to outside stimuli and markedly different lifespans indicating the epigenetic factors play an important role in gene expression and aging as well as genetic factors There is research into epigenetics of aging The ability to repair DNA double strand breaks declines with aging in mice 68 and humans 69 A set of rare hereditary genetics disorders each called progeria has been known for some time Sufferers exhibit symptoms resembling accelerated aging including wrinkled skin The cause of Hutchinson Gilford progeria syndrome was reported in the journal Nature in May 2003 70 This report suggests that DNA damage not oxidative stress is the cause of this form of accelerated aging A study indicates that aging may shift activity toward short genes or shorter transcript length and that this can be countered by interventions 71 Healthspans and aging in society edit nbsp Past and projected age of the human world population through time as of 2021 72 nbsp Healthspan lifespan gap LHG 72 nbsp Healthspan extension relies on the unison of social clinical and scientific programs or domains of work 72 Healthspan can broadly be defined as the period of one s life that one is healthy such as free of significant diseases 73 or declines of capacities e g of senses muscle endurance and cognition These paragraphs are an excerpt from Global health Multimorbidity age related diseases and aging edit With aging populations there is a rise of age related diseases which puts major burdens on healthcare systems as well as contemporary economies or contemporary economics and their appendant societal systems Healthspan extension and anti aging research seek to extend the span of health in the old as well as slow aging or its negative impacts such as physical and mental decline Modern anti senescent and regenerative technology with augmented decision making could help responsibly bridge the healthspan lifespan gap for a future of equitable global wellbeing 74 Aging is the most prevalent risk factor for chronic disease frailty and disability and it is estimated that there will be over 2 billion persons age gt 60 by the year 2050 making it a large global health challenge that demands substantial and well orchestrated or efficient efforts including interventions that alter and target the inborn aging process 75 Biological aging or the LHG comes with a great cost burden to society including potentially rising health care costs also depending on types and costs of treatments 72 76 This along with global quality of life or wellbeing highlight the importance of extending healthspans 72 Many measures that may extend lifespans may simultaneously also extend healthspans albeit that is not necessarily the case indicating that lifespan can no longer be the sole parameter of interest in related research 77 While recent life expectancy increases were not followed by parallel healthspan expansion 72 awareness of the concept and issues of healthspan lags as of 2017 73 Scientists have noted that c hronic diseases of aging are increasing and are inflicting untold costs on human quality of life 76 Interventions editThis section is an excerpt from Life extension edit Life extension is the concept of extending the human lifespan either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally settled limit of 125 years 78 Several researchers in the area along with life extensionists immortalists or longevists those who wish to achieve longer lives themselves postulate that future breakthroughs in tissue rejuvenation stem cells regenerative medicine molecular repair gene therapy pharmaceuticals and organ replacement such as with artificial organs or xenotransplantations will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition agerasia 79 The ethical ramifications if life extension becomes a possibility are debated by bioethicists The sale of purported anti aging products such as supplements and hormone replacement is a lucrative global industry For example the industry that promotes the use of hormones as a treatment for consumers to slow or reverse the aging process in the US market generated about 50 billion of revenue a year in 2009 80 The use of such hormone products has not been proven to be effective or safe 80 81 82 83 See also editAnti aging movement Antimuscarinics Dementia DNA repair Geriatrics Gerontology Heavy metals Homeostatic capacity Immortality Index of topics related to life extension Mitohormesis Old age Phenoptosis Plant senescence Programmed cell death Strategies for engineered negligible senescence SENS Sub lethal damage Transgenerational design Timeline of senescence researchReferences edit a b Kirkwood T B L 1977 Evolution of ageing Nature 270 5635 301 304 Bibcode 1977Natur 270 301K doi 10 1038 270301a0 ISSN 0028 0836 PMID 593350 S2CID 492012 Archived from the original on 15 November 2023 Retrieved 31 January 2022 a b Nelson P Masel J December 2017 Intercellular competition and the inevitability of multicellular aging Proceedings of the National Academy of Sciences of the United States of America 114 49 12982 12987 Bibcode 2017PNAS 11412982N doi 10 1073 pnas 1618854114 PMC 5724245 PMID 29087299 Aging and Gerontology Glossary Archived from the original on 19 October 2019 Retrieved 26 February 2011 Lopez Otin C Blasco MA Partridge L Serrano M Kroemer G June 2013 The hallmarks of aging Cell 153 6 1194 217 doi 10 1016 j cell 2013 05 039 PMC 3836174 PMID 23746838 Lopez Otin Carlos Blasco Maria A Partridge Linda Serrano Manuel Kroemer Guido 19 January 2023 Hallmarks of aging An expanding universe Cell 186 2 243 278 doi 10 1016 j cell 2022 11 001 ISSN 0092 8674 PMID 36599349 S2CID 255394876 Archived from the original on 17 February 2023 Retrieved 17 February 2023 a b Holmes GE Bernstein C Bernstein H September 1992 Oxidative and other DNA damages as the basis of aging a review Mutat Res 275 3 6 305 15 doi 10 1016 0921 8734 92 90034 m PMID 1383772 a b Williams GC 1957 Pleiotropy natural selection and the evolution of senescence Evolution 11 4 398 411 doi 10 2307 2406060 JSTOR 2406060 Austad SN February 2009 Comparative biology of aging The Journals of Gerontology Series A Biological Sciences and Medical Sciences 64 2 199 201 doi 10 1093 gerona gln060 PMC 2655036 PMID 19223603 Wang L Cui J Jin B Zhao J Xu H Lu Z et al January 2020 Multifeature analyses of vascular cambial cells reveal longevity mechanisms in old Ginkgo biloba trees Proceedings of the National Academy of Sciences of the United States of America 117 4 2201 2210 Bibcode 2020PNAS 117 2201W doi 10 1073 pnas 1916548117 PMC 6995005 PMID 31932448 Ackermann M Stearns SC Jenal U June 2003 Senescence in a bacterium with asymmetric division Science 300 5627 1920 doi 10 1126 science 1083532 PMID 12817142 S2CID 34770745 Stewart EJ Madden R Paul G Taddei F February 2005 Aging and death in an organism that reproduces by morphologically symmetric division PLOS Biology 3 2 e45 doi 10 1371 journal pbio 0030045 PMC 546039 PMID 15685293 Danko MJ Kozlowski J Schaible R October 2015 Unraveling the non senescence phenomenon in Hydra Journal of Theoretical Biology 382 137 49 Bibcode 2015JThBi 382 137D doi 10 1016 j jtbi 2015 06 043 PMID 26163368 Tan TC Rahman R Jaber Hijazi F Felix DA Chen C Louis EJ Aboobaker A March 2012 Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms Proceedings of the National Academy of Sciences of the United States of America 109 11 4209 14 Bibcode 2012PNAS 109 4209T doi 10 1073 pnas 1118885109 PMC 3306686 PMID 22371573 Lisenkova AA Grigorenko AP Tyazhelova TV Andreeva TV Gusev FE Manakhov AD et al February 2017 Complete mitochondrial genome and evolutionary analysis of Turritopsis dohrnii the immortal jellyfish with a reversible life cycle Molecular Phylogenetics and Evolution 107 232 238 doi 10 1016 j ympev 2016 11 007 PMID 27845203 Piraino S Boero F Aeschbach B Schmid V June 1996 Reversing the Life Cycle Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula Cnidaria Hydrozoa The Biological Bulletin 190 3 302 312 doi 10 2307 1543022 JSTOR 1543022 PMID 29227703 Vaupel JW Baudisch A Dolling M Roach DA Gampe J June 2004 The case for negative senescence Theoretical Population Biology 65 4 339 51 doi 10 1016 j tpb 2003 12 003 PMID 15136009 Vina J Borras C Miquel J 2007 Theories of ageing IUBMB Life 59 4 5 249 54 doi 10 1080 15216540601178067 PMID 17505961 Kirkwood Thomas B L Austad Steven N 2000 Why do we age Nature 408 6809 233 238 Bibcode 2000Natur 408 233K doi 10 1038 35041682 ISSN 0028 0836 PMID 11089980 S2CID 2579770 Archived from the original on 15 November 2023 Retrieved 31 January 2022 Medawar Peter Brian Sir 1952 An unsolved problem of biology Published for the College by H K Lewis amp Co Ltd OCLC 869293719 Archived from the original on 15 November 2023 Retrieved 31 January 2022 a href Template Cite book html title Template Cite book cite book a CS1 maint multiple names authors list link Rose Michael R 1991 Evolutionary biology of aging Oxford University Press ISBN 1 4237 6520 6 OCLC 228167629 Archived from the original on 15 November 2023 Retrieved 31 January 2022 Kirkwood Tom 2006 Time of Our Lives the Science of Human Aging Oxford University Press ISBN 978 0 19 802939 7 OCLC 437175125 Archived from the original on 15 November 2023 Retrieved 31 January 2022 Hammers M Richardson DS Burke T Komdeur J September 2013 The impact of reproductive investment and early life environmental conditions on senescence support for the disposable soma hypothesis Journal of Evolutionary Biology 26 9 1999 2007 doi 10 1111 jeb 12204 hdl 11370 9cc6749c f67d 40ab a253 a06650c32102 PMID 23961923 S2CID 46466320 Kirkwood TB Rose MR April 1991 Evolution of senescence late survival sacrificed for reproduction Philosophical Transactions of the Royal Society of London Series B Biological Sciences 332 1262 15 24 Bibcode 1991RSPTB 332 15K doi 10 1098 rstb 1991 0028 PMID 1677205 Atwood CS Bowen RL 2011 The reproductive cell cycle theory of aging an update Experimental Gerontology 46 2 3 100 7 doi 10 1016 j exger 2010 09 007 PMID 20851172 S2CID 20998909 Harman D July 1956 Aging a theory based on free radical and radiation chemistry Journal of Gerontology 11 3 298 300 doi 10 1093 geronj 11 3 298 hdl 2027 mdp 39015086547422 PMID 13332224 Stadtman ER August 1992 Protein oxidation and aging Science 257 5074 1220 4 Bibcode 1992Sci 257 1220S doi 10 1126 science 1355616 PMID 1355616 Archived from the original on 31 July 2021 Retrieved 21 July 2021 Sohal RS Agarwal S Dubey A Orr WC August 1993 Protein oxidative damage is associated with life expectancy of houseflies Proceedings of the National Academy of Sciences of the United States of America 90 15 7255 9 Bibcode 1993PNAS 90 7255S doi 10 1073 pnas 90 15 7255 PMC 47115 PMID 8346242 Pearl R 1928 The Rate of Living Being an Account of Some Experimental Studies on the Biology of Life Duration New York Alfred A Knopf page needed Brunet Rossinni AK Austad SN 2004 Ageing studies on bats a review Biogerontology 5 4 211 22 doi 10 1023 B BGEN 0000038022 65024 d8 PMID 15314271 S2CID 22755811 de Magalhaes JP Costa J Church GM February 2007 An analysis of the relationship between metabolism developmental schedules and longevity using phylogenetic independent contrasts The Journals of Gerontology Series A Biological Sciences and Medical Sciences 62 2 149 60 CiteSeerX 10 1 1 596 2815 doi 10 1093 gerona 62 2 149 PMC 2288695 PMID 17339640 Freedman ND Park Y Abnet CC Hollenbeck AR Sinha R May 2012 Association of coffee drinking with total and cause specific mortality The New England Journal of Medicine 366 20 1891 904 doi 10 1056 NEJMoa1112010 PMC 3439152 PMID 22591295 Yang Y Chan SW Hu M Walden R Tomlinson B 2011 Effects of some common food constituents on cardiovascular disease ISRN Cardiology 2011 397136 doi 10 5402 2011 397136 PMC 3262529 PMID 22347642 Poole Robin Kennedy Oliver J Roderick Paul Fallowfield Jonathan A Hayes Peter C Parkes Julie 22 November 2017 Coffee consumption and health umbrella review of meta analyses of multiple health outcomes BMJ 359 j5024 doi 10 1136 bmj j5024 ISSN 0959 8138 PMC 5696634 PMID 29167102 O Keefe James H DiNicolantonio James J Lavie Carl J 1 May 2018 Coffee for Cardioprotection and Longevity Progress in Cardiovascular Diseases 61 1 38 42 doi 10 1016 j pcad 2018 02 002 ISSN 0033 0620 PMID 29474816 Grosso Giuseppe Godos Justyna Galvano Fabio Giovannucci Edward L 21 August 2017 Coffee Caffeine and Health Outcomes An Umbrella Review Annual Review of Nutrition 37 1 131 156 doi 10 1146 annurev nutr 071816 064941 ISSN 0199 9885 PMID 28826374 Dirks Naylor Amie J 15 December 2015 The benefits of coffee on skeletal muscle Life Sciences 143 182 186 doi 10 1016 j lfs 2015 11 005 ISSN 0024 3205 PMID 26546720 Reis Caio E G Dorea Jose G da Costa Teresa H M 1 July 2019 Effects of coffee consumption on glucose metabolism A systematic review of clinical trials Journal of Traditional and Complementary Medicine 9 3 184 191 doi 10 1016 j jtcme 2018 01 001 ISSN 2225 4110 PMC 6544578 PMID 31193893 Loureiro Lais Monteiro Rodrigues Reis Caio Eduardo Goncalves Costa Teresa Helena Macedo da 1 May 2018 Effects of Coffee Components on Muscle Glycogen Recovery A Systematic Review International Journal of Sport Nutrition and Exercise Metabolism 28 3 284 293 doi 10 1123 ijsnem 2017 0342 ISSN 1543 2742 PMID 29345166 Bernstein H Payne CM Bernstein C Garewal H Dvorak K 2008 Cancer and aging as consequences of un repaired DNA damage In Kimura H Suzuki A eds New Research on DNA Damage Nova Science Publishers pp 1 47 ISBN 978 1604565812 Archived from the original on 15 November 2023 Retrieved 4 February 2016 Pan MR Li K Lin SY Hung WC May 2016 Connecting the Dots From DNA Damage and Repair to Aging International Journal of Molecular Sciences 17 5 685 doi 10 3390 ijms17050685 PMC 4881511 PMID 27164092 a b Schumacher Bjorn Pothof Joris Vijg Jan Hoeijmakers Jan H J April 2021 The central role of DNA damage in the ageing process Nature 592 7856 695 703 doi 10 1038 s41586 021 03307 7 ISSN 1476 4687 PMC 9844150 PMID 33911272 Gensler H L Bernstein H September 1981 DNA damage as the primary cause of aging The Quarterly Review of Biology 56 3 279 303 doi 10 1086 412317 ISSN 0033 5770 PMID 7031747 S2CID 20822805 Spencer RL Hutchison KE 1999 Alcohol aging and the stress response PDF Alcohol Research amp Health 23 4 272 83 PMC 6760387 PMID 10890824 Archived from the original PDF on 11 December 2018 Retrieved 8 April 2008 Fabian D Flatt T 2011 The Evolution of Aging Scitable Nature Publishing Group Archived from the original on 31 March 2019 Retrieved 10 December 2014 Medawar PB 1946 Old age and natural death Modern Quarterly 1 30 56 Medawar PB 1952 An Unsolved Problem of Biology London H K Lewis amp Co Ltd page needed Liu Xiaoqian Liu Zunpeng Wu Zeming Ren Jie Fan Yanling Sun Liang Cao Gang Niu Yuyu Zhang Baohu Ji Qianzhao Jiang Xiaoyu Wang Cui Wang Qiaoran Ji Zhejun Li Lanzhu Esteban Concepcion Rodriguez Yan Kaowen Li Wei Cai Yusheng Wang Si Zheng Aihua Zhang Yong E Tan Shengjun Cai Yingao Song Moshi Lu Falong Tang Fuchou Ji Weizhi Zhou Qi Belmonte Juan Carlos Izpisua Zhang Weiqi Qu Jing Liu Guang Hui 19 January 2023 Resurrection of endogenous retroviruses during aging reinforces senescence Cell 186 2 287 304 e26 doi 10 1016 j cell 2022 12 017 ISSN 0092 8674 PMID 36610399 S2CID 232060038 Expert explanation of the study Aging and Retroviruses Science Archived from the original on 17 February 2023 Retrieved 17 February 2023 Smith J A Daniel R Stem Cells and Aging A Chicken Or Egg Issue Aging and Disease 2012 Jun Vol 3 Number 3 260 268 Mahla RS 2016 Stem cells application in regenerative medicine and disease threpeutics International Journal of Cell Biology 2016 7 19 doi 10 1155 2016 6940283 PMC 4969512 PMID 27516776 Rossi DJ Bryder D Seita J Nussenzweig A Hoeijmakers J Weissman IL 2007 Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age Nature 447 7145 725 9 Bibcode 2007Natur 447 725R doi 10 1038 nature05862 PMID 17554309 S2CID 4416445 a b Beerman I Seita J Inlay MA Weissman IL Rossi DJ 2014 Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle Cell Stem Cell 15 1 37 50 doi 10 1016 j stem 2014 04 016 PMC 4082747 PMID 24813857 a b Nijnik A Woodbine L Marchetti C Dawson S Lambe T Liu C Rodrigues NP Crockford TL Cabuy E Vindigni A Enver T Bell JI Slijepcevic P Goodnow CC Jeggo PA Cornall RJ 2007 DNA repair is limiting for haematopoietic stem cells during ageing Nature 447 7145 686 90 Bibcode 2007Natur 447 686N doi 10 1038 nature05875 PMID 17554302 S2CID 4332976 Research may reveal why people can suddenly become frail in their 70s The Guardian 1 June 2022 Retrieved 18 July 2022 Mitchell Emily Spencer Chapman Michael Williams Nicholas Dawson Kevin J Mende Nicole Calderbank Emily F Jung Hyunchul Mitchell Thomas Coorens Tim H H Spencer David H Machado Heather Lee Six Henry Davies Megan Hayler Daniel Fabre Margarete A Mahbubani Krishnaa Abascal Federico Cagan Alex Vassiliou George S Baxter Joanna Martincorena Inigo Stratton Michael R Kent David G Chatterjee Krishna Parsy Kourosh Saeb Green Anthony R Nangalia Jyoti Laurenti Elisa Campbell Peter J June 2022 Clonal dynamics of haematopoiesis across the human lifespan Nature 606 7913 343 350 Bibcode 2022Natur 606 343M doi 10 1038 s41586 022 04786 y ISSN 1476 4687 PMC 9177428 PMID 35650442 Kolata Gina 14 July 2022 As Y Chromosomes Vanish With Age Heart Risks May Grow The New York Times Retrieved 21 August 2022 Sano Soichi Horitani Keita Ogawa Hayato Halvardson Jonatan Chavkin Nicholas W Wang Ying Sano Miho Mattisson Jonas Hata Atsushi Danielsson Marcus Miura Yura Emiri Zaghlool Ammar Evans Megan A Fall Tove De Hoyos Henry N Sundstrom Johan Yura Yoshimitsu Kour Anupreet Arai Yohei Thel Mark C Arai Yuka Mychaleckyj Josyf C Hirschi Karen K Forsberg Lars A Walsh Kenneth 15 July 2022 Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality Science 377 6603 292 297 Bibcode 2022Sci 377 292S doi 10 1126 science abn3100 ISSN 0036 8075 PMC 9437978 PMID 35857592 Gasmi A Chirumbolo S Peana M Mujawdiya PK Dadar M Menzel A Bjorklund G 17 September 2020 Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures Current Medicinal Chemistry 28 8 1471 1488 doi 10 2174 0929867327999200917150652 PMID 32942969 S2CID 221789280 Baker GT Sprott RL 1988 Biomarkers of aging Experimental Gerontology 23 4 5 223 39 doi 10 1016 0531 5565 88 90025 3 PMID 3058488 S2CID 31039588 Archived from the original on 24 October 2021 Retrieved 12 July 2019 Van Neste D Tobin DJ 2004 Hair cycle and hair pigmentation dynamic interactions and changes associated with aging Micron 35 3 193 200 doi 10 1016 j micron 2003 11 006 PMID 15036274 Miller RA April 2001 Biomarkers of aging prediction of longevity by using age sensitive T cell subset determinations in a middle aged genetically heterogeneous mouse population The Journals of Gerontology Series A Biological Sciences and Medical Sciences 56 4 B180 6 doi 10 1093 gerona 56 4 b180 PMC 7537444 PMID 11283189 Horvath S 2013 DNA methylation age of human tissues and cell types Genome Biology 14 10 R115 doi 10 1186 gb 2013 14 10 r115 PMC 4015143 PMID 24138928 Putin E Mamoshina P Aliper A Korzinkin M Moskalev A Kolosov A et al May 2016 Deep biomarkers of human aging Application of deep neural networks to biomarker development Aging 8 5 1021 33 doi 10 18632 aging 100968 PMC 4931851 PMID 27191382 Peters MJ Joehanes R Pilling LC Schurmann C Conneely KN Powell J et al October 2015 The transcriptional landscape of age in human peripheral blood Nature Communications 6 8570 Bibcode 2015NatCo 6 8570 doi 10 1038 ncomms9570 PMC 4639797 PMID 26490707 Yin Chenzhong Imms Phoebe Cheng Mingxi et al 10 January 2023 Anatomically interpretable deep learning of brain age captures domain specific cognitive impairment Proceedings of the National Academy of Sciences 120 2 e2214634120 Bibcode 2023PNAS 12014634Y doi 10 1073 pnas 2214634120 ISSN 0027 8424 PMC 9926270 PMID 36595679 University press release How old is your brain really AI powered analysis accurately reflects risk of cognitive decline and Alzheimer s disease University of Southern California via medicalxpress com Archived from the original on 17 February 2023 Retrieved 17 February 2023 News article about the study KI kann wahres Alter des Hirns bestimmen Deutschlandfunk Nova in German Archived from the original on 17 February 2023 Retrieved 17 February 2023 Sayed Nazish Huang Yingxiang Nguyen Khiem Krejciova Rajaniemi Zuzana Grawe Anissa P Gao Tianxiang Tibshirani Robert Hastie Trevor Alpert Ayelet Cui Lu Kuznetsova Tatiana Rosenberg Hasson Yael Ostan Rita Monti Daniela Lehallier Benoit Shen Orr Shai S Maecker Holden T Dekker Cornelia L Wyss Coray Tony Franceschi Claudio Jojic Vladimir Haddad Francois Montoya Jose G Wu Joseph C Davis Mark M Furman David July 2021 An inflammatory aging clock iAge based on deep learning tracks multimorbidity immunosenescence frailty and cardiovascular aging Nature Aging 1 7 598 615 doi 10 1038 s43587 021 00082 y ISSN 2662 8465 PMC 8654267 PMID 34888528 News article about the study Tool that calculates immune system age could predict frailty and disease New Atlas 13 July 2021 Archived from the original on 26 July 2021 Retrieved 26 July 2021 Fitzgerald K N Hodges R Hanes D Stack E Cheishvili D Szyf M Henkel J Twedt M W Giannopoulou D Herdell J Logan S Bradley R 2021 Potential reversal of epigenetic age using a diet and lifestyle intervention a pilot randomized clinical trial Aging 13 7 9419 9432 doi 10 18632 aging 202913 PMC 8064200 PMID 33844651 Archived from the original on 2 June 2021 Retrieved 28 June 2021 Ryley J Pereira Smith OM 2006 Microfluidics device for single cell gene expression analysis in Saccharomyces cerevisiae Yeast 23 14 15 1065 73 doi 10 1002 yea 1412 PMID 17083143 S2CID 31356425 Vaidya A Mao Z Tian X Spencer B Seluanov A Gorbunova V July 2014 Knock in reporter mice demonstrate that DNA repair by non homologous end joining declines with age PLOS Genet 10 7 e1004511 doi 10 1371 journal pgen 1004511 PMC 4102425 PMID 25033455 Li Z Zhang W Chen Y Guo W Zhang J Tang H Xu Z Zhang H Tao Y Wang F Jiang Y Sun FL Mao Z November 2016 Impaired DNA double strand break repair contributes to the age associated rise of genomic instability in humans Cell Death Differ 23 11 1765 77 doi 10 1038 cdd 2016 65 PMC 5071568 PMID 27391797 Mounkes LC Kozlov S Hernandez L Sullivan T Stewart CL May 2003 A progeroid syndrome in mice is caused by defects in A type lamins Nature 423 6937 298 301 Bibcode 2003Natur 423 298M doi 10 1038 nature01631 PMID 12748643 S2CID 4360055 Archived from the original on 30 May 2022 Retrieved 21 July 2021 Stoeger Thomas Grant Rogan A McQuattie Pimentel Alexandra C Anekalla Kishore R Liu Sophia S Tejedor Navarro Heliodoro Singer Benjamin D Abdala Valencia Hiam Schwake Michael Tetreault Marie Pier Perlman Harris Balch William E Chandel Navdeep S Ridge Karen M Sznajder Jacob I Morimoto Richard I Misharin Alexander V Budinger G R Scott Nunes Amaral Luis A December 2022 Aging is associated with a systemic length associated transcriptome imbalance Nature Aging 2 12 1191 1206 doi 10 1038 s43587 022 00317 6 ISSN 2662 8465 PMC 10154227 PMID 37118543 University press release Aging is driven by unbalanced genes finds AI analysis of multiple species Northwestern University via phys org Archived from the original on 2 February 2023 Retrieved 18 January 2023 News article about the study Kwon Diana Aging Is Linked to More Activity in Short Genes Than in Long Genes Scientific American Archived from the original on 17 January 2023 Retrieved 18 January 2023 a b c d e f Garmany Armin Yamada Satsuki Terzic Andre 23 September 2021 Longevity leap mind the healthspan gap npj Regenerative Medicine 6 1 57 doi 10 1038 s41536 021 00169 5 ISSN 2057 3995 PMC 8460831 PMID 34556664 Non profit hospital press release Buckles Susan A regenerative reset for aging Center for Regenerative Biotherapeutics Mayo Clinic Archived from the original on 1 March 2023 Retrieved 1 March 2023 a b Healthspan is more important than lifespan so why don t more people know about it Institute for Public Health Washington University in St Louis publichealth wustl edu Archived from the original on 1 March 2023 Retrieved 1 March 2023 Garmany A Yamada S Terzic A September 2021 Longevity leap mind the healthspan gap npj Regenerative Medicine 6 1 57 doi 10 1038 s41536 021 00169 5 PMC 8460831 PMID 34556664 Farrelly C November 2022 Aging Equality and the Human Healthspan HEC Forum 1 19 doi 10 1007 s10730 022 09499 3 PMC 9644010 PMID 36348214 a b Hansen Malene Kennedy Brian K 1 August 2016 Does Longer Lifespan Mean Longer Healthspan Trends in Cell Biology 26 8 565 568 doi 10 1016 j tcb 2016 05 002 ISSN 0962 8924 PMC 4969078 PMID 27238421 Bansal Ankita Zhu Lihua J Yen Kelvin Tissenbaum Heidi A 20 January 2015 Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants Proceedings of the National Academy of Sciences 112 3 E277 86 Bibcode 2015PNAS 112E 277B doi 10 1073 pnas 1412192112 ISSN 0027 8424 PMC 4311797 PMID 25561524 Turner BS 2009 Can We Live Forever A Sociological and Moral Inquiry Anthem Press p 3 agerasia Oxford English Dictionary Online ed Oxford University Press Subscription or participating institution membership required a b Japsen B 15 June 2009 AMA report questions science behind using hormones as anti aging treatment The Chicago Tribune Retrieved 17 July 2009 Holliday R April 2009 The extreme arrogance of anti aging medicine Biogerontology 10 2 223 228 doi 10 1007 s10522 008 9170 6 PMID 18726707 S2CID 764136 Olshansky SJ Hayflick L Carnes BA August 2002 Position statement on human aging The Journals of Gerontology Series A Biological Sciences and Medical Sciences 57 8 B292 B297 CiteSeerX 10 1 1 541 3004 doi 10 1093 gerona 57 8 B292 PMID 12145354 Warner H Anderson J Austad S Bergamini E Bredesen D Butler R et al November 2005 Science fact and the SENS agenda What can we reasonably expect from ageing research EMBO Reports 6 11 1006 1008 doi 10 1038 sj embor 7400555 PMC 1371037 PMID 16264422 External links edit nbsp Look up senescence in Wiktionary the free dictionary nbsp Wikimedia Commons has media related to Senescence Senescence at Curlie Retrieved from https en wikipedia org w index php title Senescence amp oldid 1193875596, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.