Senescence

Senescence (

Environmental

Organismal senescence is the aging of whole organisms. Actuarial senescence can be defined as an increase in mortality 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.

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.

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]

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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.

One theory was proposed by

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]

The disposable soma theory of aging was proposed by

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]

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]

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

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.^[42] Slower rate of accumulation of DNA damage as measured by the DNA damage marker gamma H2AX in leukocytes was found to correlate with longer lifespans in comparisons of dolphins, goats, reindeer, American flamingos and griffon vultures.^[43] DNA damage-induced epigenetic alterations, such as DNA methylation and many histone modifications, appear to be of particular importance to the aging process.^[42] Evidence for the theory that DNA damage is the fundamental cause of aging was first reviewed in 1981.^[44]

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.^[45]

Peter Medawar formalised this observation in his mutation accumulation theory of aging.^[46][47] "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.

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".^[48]

Hematopoietic mosaic loss of chromosome Y

If different individuals age at different rates, then fecundity, mortality, and functional capacity might be better predicted by biomarkers than by chronological age.^[58][59] However, graying of hair,^[60] 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.^[61]

There is interest in an epigenetic clock as a biomarker of aging, based on its ability to predict human chronological age.^[62] Basic blood biochemistry and cell counts can also be used to accurately predict the chronological age.^[63] It is also possible to predict the human chronological age using transcriptomic aging clocks.^[64]

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

Aging clocks have been used to evaluate impacts of interventions on humans, including combination therapies.^{[67][additional citation(s) needed]} Employing aging clocks to identify and evaluate longevity interventions represents a fundamental goal in aging biology research. However, achieving this goal requires overcoming numerous challenges and implementing additional validation steps.^[68][69]

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.

The ability to repair DNA double-strand breaks declines with aging in mice^[71] and humans.^[72]

A set of rare hereditary (

A study indicates that aging may shift activity toward short genes or shorter transcript length and that this can be countered by interventions.[74]

Healthspan can broadly be defined as the period of one's life that one is

These paragraphs are an excerpt from Global health § Multimorbidity, age-related diseases and aging.[edit]

wellbeing, highlight the importance of extending healthspans.^[75]

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.[80] While recent life expectancy increases were not followed by "parallel" healthspan expansion,^[75] awareness of the concept and issues of healthspan lags as of 2017.^[76] Scientists have noted that "[c]hronic diseases of aging are increasing and are inflicting untold costs on human quality of life".^[79]

Interventions

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

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.^[83] The use of such hormone products has not been proven to be effective or safe.^{[83][84][85][86]}

See also

• Anti-aging movement
• Antimuscarinics
• Dementia
• DNA repair
• Geriatrics
• Gerontology
• 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 research

References

1. ^
   S2CID 492012. Archived
   from the original on 15 November 2023. Retrieved 31 January 2022.
2. ^
   PMID 29087299
   .
3. ^ "Aging and Gerontology Glossary". Archived from the original on 19 October 2019. Retrieved 26 February 2011.
4. PMID 23746838
   .
5. S2CID 255394876
   .
6. ^
   PMID 1383772
   .
7. ^
   JSTOR 2406060
   .
8. PMID 19223603
   .
9. PMID 31932448
   .
10. S2CID 34770745
    .
11. PMID 15685293
    .
12. PMID 26163368
    .
13. PMID 22371573
    .
14. PMID 27845203
    .
15. PMID 29227703
    .
16. PMID 15136009
    .
17. PMID 17505961
    .
18. S2CID 2579770. Archived
    from the original on 15 November 2023. Retrieved 31 January 2022.
19. OCLC 869293719
    .
20. OCLC 228167629. Archived
    from the original on 15 November 2023. Retrieved 31 January 2022.
21. OCLC 437175125. Archived
    from the original on 15 November 2023. Retrieved 31 January 2022.
22. S2CID 46466320
    .
23. PMID 1677205
    .
24. S2CID 20998909
    .
25. PMID 13332224
    .
26. PMID 1355616. Archived
    from the original on 31 July 2021. Retrieved 21 July 2021.
27. PMID 8346242
    .
28. LCCN 28000834.^{[page needed}
    ]
29. S2CID 22755811
    .
30. PMID 17339640
    .
31. PMID 22591295
    .
32. PMID 22347642
    .
33. PMID 29167102
    .
34. PMID 29474816
    .
35. PMID 28826374
    .
36. PMID 26546720
    .
37. PMID 31193893
    .
38. PMID 29345166
    .
39. ISBN 978-1604565812. Archived
    from the original on 15 November 2023. Retrieved 4 February 2016.
40. PMID 27164092
    .
41. PMID 10890824. Archived from the original
    (PDF) on 11 December 2018. Retrieved 8 April 2008.
42. ^
    PMID 33911272
    .
43. PMID 31730540
    .
44. S2CID 20822805
    .
45. ^ Fabian D, Flatt T (2011). "The Evolution of Aging" (PDF). Nature Education.
46. ^ Medawar PB (1946). "Old age and natural death". Modern Quarterly. 1: 30–56.
47. ^ Medawar 1952^{[page needed]}
48. S2CID 232060038
    .
    • Expert explanation of the study: "Aging and Retroviruses". Science. Archived from the original on 17 February 2023. Retrieved 17 February 2023.
49. ^ 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.
50. ^ Mahla RS (2016). "Stem cells application in regenerative medicine and disease threpeutics". International Journal of Cell Biology. 2016 (7): 19.
    PMID 27516776
    .
51. S2CID 4416445
    .
52. ^
    PMID 24813857
    .
53. ^
    S2CID 4332976
    .
54. ^ "Research may reveal why people can suddenly become frail in their 70s". The Guardian. 1 June 2022. Retrieved 18 July 2022.
55. PMID 35650442
    .
56. ^ Kolata G (14 July 2022). "As Y Chromosomes Vanish With Age, Heart Risks May Grow". The New York Times. Retrieved 21 August 2022.
57. PMID 35857592
    .
58. S2CID 221789280
    .
59. S2CID 31039588. Archived
    from the original on 24 October 2021. Retrieved 12 July 2019.
60. PMID 15036274
    .
61. PMID 11283189
    .
62. PMID 37253906
    .
63. PMID 27191382
    .
64. PMID 26490707
    .
65. 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.
66. 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.
67. PMID 33844651. Archived
    from the original on 2 June 2021. Retrieved 28 June 2021.
68. PMID 37657418
    .
69. PMID 38355974
    .
70. S2CID 31356425
    .
71. PMID 25033455
    .
72. PMID 27391797
    .
73. S2CID 4360055. Archived
    from the original on 30 May 2022. Retrieved 21 July 2021 – via Zenodo.
74. PMID 37118543
    .
    • University press release: "Aging is driven by unbalanced genes, finds AI analysis of multiple species". Northwestern University. 9 December 2022. Archived from the original on 2 February 2023. Retrieved 18 January 2023 – via phys.org.
    • News article about the study: Kwon D (6 January 2023). "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.
75. ^
    PMID 34556664
    .
    • Non-profit hospital press release: Buckles S (7 October 2021). "A regenerative reset for aging » Center for Regenerative Biotherapeutics". Mayo Clinic. Archived from the original on 1 March 2023. Retrieved 1 March 2023.
76. ^ ^{a b} Peterson T (30 May 2017). "Healthspan is more important than lifespan, so why don't more people know about it?". Institute for Public Health. Washington University in St. Louis. Harvey A. Friedman Center for Aging. Archived from the original on 1 March 2023. Retrieved 1 March 2023.
77. PMID 34556664
    .
78. PMID 36348214
    .
79. ^
    PMID 27238421
    .
80. PMID 25561524
    .
81. ^ Turner BS (2009). Can We Live Forever? A Sociological and Moral Inquiry. Anthem Press. p. 3.
82. ^ "agerasia". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
83. ^
    The Chicago Tribune
    . Retrieved 17 July 2009.
84. S2CID 764136
    .
85. PMID 12145354
    .
86. PMID 16264422.{{cite journal}}: CS1 maint: overridden setting (link
    )

External links

Look up senescence in Wiktionary, the free dictionary.

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