Senescence

Senescence (/sɪˈnɛsəns/) or biological aging is the gradual

deterioration of functional characteristics. The word
senescence can refer either to 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.

Senescence is the inevitable fate of all multicellular

organisms with germ-soma separation,[1] but it can be
delayed. The discovery, in 1934, that calorie restriction can
extend lifespan by 50% in rats, and the existence of species
having negligible senescence and potentially immortal An elderly man at a nursing home in Norway
species such as Hydra, have motivated research into
delaying senescence and thus age-related diseases. Rare
human mutations can causeaccelerated aging diseases.

Environmental factors may affect aging, for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of
the body may age at different rates. Two organisms of the same species can also age at different rates, making biological aging and
chronological aging distinct concepts.

There are a number of hypotheses as towhy senescence occurs.

Contents
Definition and characteristics
Variation among species
Evolutionary theories of aging
Mutation accumulation
Antagonistic pleiotropy
Adaptive aging
Cellular senescence
Cancer versus cellular senescence tradeoff theory of aging
Chemical damage
Biomarkers of aging
Genetic determinants of aging
See also
References
External links

Definition and characteristics

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 mortalitysays that that the age-dependent component of the
mortality rate increases exponentiallywith 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, and altered intercellular
communication.[2] 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]
Supercentenarian Ann Pouder (8
The environment induces damage at various levels, e.g. damage to DNA, and damage to April 1807 – 10 July 1917)
tissues and cells by oxygen radicals (widely known as free radicals), and some of this photographed on her 110th
damage is not repaired and thus accumulates with time. Cloning from somatic cells birthday. A heavily lined face is
common in human senescence.
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.

The evolutionary theorist George Williams wrote, "It is remarkable that after a seemingly miraculous feat of morphogenesis, a
[4]
complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed."

Variation among species

Differences rates of aging, i.e. 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 while ahuman is elderly at 80 years.[5]

Almost all organisms senesce, including bacteria for which we able to distinguish subtle asymmetries between "mother" and
"daughter" cells upon cell division, with the mother cell experiencing aging while the daughter is rejuvenated. Senescence has been
so far undetectable in a handful of species (negligible senescence), such as those in the genus Hydra. Planarian flatworms have
"apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult stem cells."[6] These
organisms may be biologically immortal, meaning not that they do not die, but that their death rate does not increase with age. Some
species exhibit "negative senescence", in which fecundity increases and/or mortality falls with age, due to the advantages of increased
body size with age.[7]

Evolutionary theories of aging

Mutation accumulation
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, agenetic load of late-acting deleterious mutations could be substantial at
mutation-selection balance. This concept came to be known as theselection shadow.[8]
Peter Medawar formalised this observation in his mutation accumulation theory of aging.[9][10] "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". The 'real
hazards of mortality' such as predation, disease, and accidents, are known 'extrinsic mortality', and mean that even a population with
negligible senescence will have fewer individuals alive in older age groups.

Antagonistic pleiotropy
Another evolutionary theory of aging was proposed by George C. Williams[11] 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.

An important example of antagonistic pleiotropy is the trad-off between investing resources in reproduction, rather than maintenance
of the body (the "Disposable Soma" theory[12] ).

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

[13]
The reproductive-cell cycle theorysuggests that aging is regulated by changes in hormonal signaling over the lifespan.

Cellular senescence
Cells accumulate damage over time, but this may be counterbalanced by natural selection to remove damaged cells. In particular
DNA damage, e.g. due to reactive oxygen species, leads to the accumulation of harmfulsomatic mutations.[14]

In most multicellular species, somatic cells eventually experience replicative senescence and are unable to divide. This can prevent
highly mutated cells from becoming cancerous. In culture, fibroblasts can reach a maximum of 50 cell divisions; this maximum is
known as the Hayflick limit.[15] Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage
response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of
oncogenes and cell-cell fusion, independent of telomere length.

The cellular senescence theory of aging posits that organismal aging is a consequence of the accumulation of less physiological
useful senescent cells. In agreement with this, the experimental elimination of senescent cells from transgenic progeroid mice[16] and
non-progeroid, naturally-aged mice[17][18][19] led to greater resistance against aging-associated diseases. Ectopic expression of the
embryonic transcription factor, NANOG, is shown to reverse senescence and restore the proliferation and differentiation potential of
senescent stem cells.[20][21][22][23][24]

Senescent cells can undergo conversion to an immunogenic phenotype that enables them to be eliminated by the immune system.[25]
This phenotype consists of a pro-inflammatory secretome, the up-regulation of immuneligands, a pro-survival response, promiscuous
gene expression (pGE) and stain positive for senescence-associated β-galactosidase activity.[26] The nucleus of senescent cells is
characterized by senescence-associated heterochromatin foci (SAHF) and DNA segments with chromatin alterations reinforcing
senescence (DNA-SCARS).[27] Senescent cells affect tumour suppression, wound healing and possibly embryonic/placental
[28]
development and a pathological role in age-related diseases.
In many organisms, there is asymmetric cell division, e.g. a stem cell dividing
to produce one stem cell and one non-stem cell. The cellular debris that cells
accumulate is not evenly divided between the new cells when they divide.
Instead more of the damage is passed to one of the cells, leaving the other cell
rejuvenated.[29] One lineage then undergoes cellular senescence faster than the
other.

Cancer cells avoid replicative senescence to become immortal. In about 85%

of tumors, this evasion of cellular senescence is the result of up-activation of
their telomerase genes.[30]

Cancer versus cellular senescence

tradeoff theory of aging
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.[1]
Cellular senescence
(upper) Primary mouse embryonic
Chemical damage fibroblast cells (MEFs) before senescence.
Spindle-shaped. (lower) MEFs became
One of the earliest aging theories was the Rate of Living Hypothesis described
senescent after passages. Cells grow
by Raymond Pearl in 1928[31] (based on earlier work by Max Rubner), which larger, flatten shape and expressed
states that fast basal metabolic rate corresponds to short maximum life span. senescence-associatedβ-galactosidase
(SABG, blue areas), a marker of cellular
While there may be some validity to the idea that for various types of specific senescence.
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. 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.[32] 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.[33] (For a critique of the Rate of Living Hypothesis see Living fast,
dying when?[34] )

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 Elderly Klamath woman
responsible for aging. The damage can include breakage of biopolymer chains, cross- photographed by Edward S.
Curtis in 1924
linking of biopolymers, or chemical attachment of unnatural substituents (haptens) to
biopolymers.

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. 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 dietarypolyphenol antioxidants, for example in coffee,[35] red wine and tea.[36]

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 termedglycoxidation.

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 renal 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.

It is believed that the impact of alcohol on aging can be partly explained by alcohol's activation of the HPA axis, which stimulates
[37]
glucocorticoid secretion, long-term exposure to which produces symptoms of aging.

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.[38] However, graying of hair,[39] 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
[40]
to give good predictions of the expected lifespan of middle-aged mice.

There is interest in an epigenetic clock as a biomarker of aging, based on its ability to predict human chronological age.[41] Basic
blood biochemistry and cell counts can also be used to accurately predict the chronological age.[42] It is also possible to predict the
[43]
human chronological age using the transcriptomic aging clocks.

Genetic determinants 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.[44] 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.

A set of rare hereditary (genetic) 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.[45] This report suggests that DNA damage, not oxidative stress, is the cause of this form of accelerated
aging.

See also
Ageing
 Aging brain
Aging-associated diseases
Anti-aging medicine
Anti-aging movement
DNA repair
Free radicals
Genetics of aging
Geriatrics
Gerontology
Homeostatic capacity
Immortality
Indefinite lifespan
Life extension
Index of topics related to life extension
Mitohormesis
Old age
Oxidative stress
Phenoptosis
Plant senescence
Programmed cell death
Regenerative medicine
Rejuvenation
SAGE KE
Stem cell theory of aging
Strategies for Engineered Negligible Senescence(SENS)
Sub-lethal damage
Timeline of senescence research
Transgenerational design

References
1. Nelson, Paul; Masel, Joanna (5 December 2017). "Intercellular competition and the inevitability of multicellular
aging". Proceedings of the National Academy of Sciences
. 114 (49): 12982–12987. doi:10.1073/pnas.1618854114
(https://doi.org/10.1073%2Fpnas.1618854114) .
2. Lopez-Otin, C; et al. (2013). "The hallmarks of aging"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174). Cell.
153 (6): 1194–217. doi:10.1016/j.cell.2013.05.039(https://doi.org/10.1016%2Fj.cell.2013.05.039) . PMC 3836174 (htt
ps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174). PMID 23746838 (https://www.ncbi.nlm.nih.gov/pubmed/2374
6838).
3. "Aging and Gerontology Glossary"(http://www.senescence.info/glossary.html). Retrieved 26 February 2011.
4. Williams, G.C. (1957). "Pleiotropy, natural selection, and the evolution of senescence".Evolution. 11 (4): 398–411.
doi:10.2307/2406060 (https://doi.org/10.2307%2F2406060). JSTOR 2406060 (https://www.jstor.org/stable/2406060).
5. Austad, S (2009). "Comparative Biology of Aging"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2655036). J
Gerontol a Biol Sci Med Sci. 64 (2): 199–201. doi:10.1093/gerona/gln060(https://doi.org/10.1093%2Fgerona%2Fgln
060). PMC 2655036 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2655036). PMID 19223603 (https://www.ncbi.nl
m.nih.gov/pubmed/19223603).
6. Thomas C. J. Tan; Ruman Rahman; Farah Jaber-Hijazi; Daniel A. Felix; Chen Chen; Edward J. Louis & Aziz
Aboobaker (February 2012)."Telomere maintenance and telomerase activity are differentially regulated in asexual
and sexual worms" (http://www.pnas.org/content/early/2012/02/22/1118885109.full.pdf+html). PNAS. 109 (9): 4209–
4214. doi:10.1073/pnas.1118885109(https://doi.org/10.1073%2Fpnas.1118885109) . PMC 3306686 (https://www.nc
bi.nlm.nih.gov/pmc/articles/PMC3306686). PMID 22371573 (https://www.ncbi.nlm.nih.gov/pubmed/22371573).
7. W. Vaupel, James; Baudisch, Annette; Dölling, Martin; A. Roach, Deborah; Gampe, Jutta (June 2004). "The case for
negative senescence".Theoretical Population Biology. 65 (4): 339–351. doi:10.1016/j.tpb.2003.12.003(https://doi.or
g/10.1016%2Fj.tpb.2003.12.003).
 8. Fabian, Daniel; Flatt, Thomas (2011)."The Evolution of Aging"(http://www.nature.com/scitable/knowledge/library/the
-evolution-of-aging-23651151). Scitable. Nature Publishing Group. Retrieved December 9, 2014.
9. Medawar PB (1946). "Old age and natural death".Modern Quarterly. 1: 30–56.
10. Medawar, Peter B. (1952). An Unsolved Problem of Biology. London: H. K. Lewis.
11. Williams, George C. (December 1957)."Pleiotropy, Natural Selection, and the Evolution of Senescence" (http://www.
devonescent.org/pdfs/Williams57.pdf)(PDF). Evolution. 11 (4): 398–411. doi:10.2307/2406060 (https://doi.org/10.23
07%2F2406060). JSTOR 2406060 (https://www.jstor.org/stable/2406060).
12. Kirkwood TB (November 1977). "Evolution of ageing".Nature. 270 (5635): 301–4. doi:10.1038/270301a0 (https://doi.
org/10.1038%2F270301a0). PMID 593350 (https://www.ncbi.nlm.nih.gov/pubmed/593350).
13. Bowen RL; Atwood CS (2011). "The reproductive-cell cycle theory of aging: an update". Experimental Gerontology.
46 (2): 100–7. doi:10.1016/j.exger.2010.09.007 (https://doi.org/10.1016%2Fj.exger.2010.09.007). PMID 20851172 (h
ttps://www.ncbi.nlm.nih.gov/pubmed/20851172).
14. Bernstein, H; Payne, CM; Bernstein, C; Garewal, H; Dvorak, K (2008)."Cancer and aging as consequences of un-
repaired DNA damage."(https://www.novapublishers.com/catalog/product_info.php?products_id=43247). In Kimura,
Honoka; Suzuki, Aoi. New Research on DNA Damage(https://books.google.com/books?id=arjZMwAACAAJ&pg=P A
1). Nova Science Publishers. pp. 1–47.ISBN 978-1604565812.
15. Hayflick L; Moorhead PS (December 1961). "The serial cultivation of human diploid cell strains".
Exp. Cell Res. 25
(3): 585–621. doi:10.1016/0014-4827(61)90192-6(https://doi.org/10.1016%2F0014-4827%2861%2990192-6) .
PMID 13905658 (https://www.ncbi.nlm.nih.gov/pubmed/13905658).
16. Baker, D.; Wijshake, T.; Tchkonia, T.; LeBrasseur, N.; Childs, B.; van de Sluis, B.; Kirkland, J.; van Deursen, J. (10
November 2011). "Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders" (https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC3468323). Nature. 479 (7372): 232–6. doi:10.1038/nature10600 (https://doi.org/1
0.1038%2Fnature10600). PMC 3468323 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468323). PMID 22048312
(https://www.ncbi.nlm.nih.gov/pubmed/22048312).
17. Xu, M; Palmer, AK; Ding, H; Weivoda, MM; Pirtskhalava, T; White, TA; Sepe, A; Johnson, KO; Stout, MB; Giorgadze,
N; Jensen, MD; LeBrasseur, NK; Tchkonia, T; Kirkland, JL (2015). "Targeting senescent cells enhances adipogenesis
and metabolic function in old age"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758946). eLife. 4: e12997.
doi:10.7554/eLife.12997 (https://doi.org/10.7554%2FeLife.12997). PMC 4758946 (https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC4758946). PMID 26687007 (https://www.ncbi.nlm.nih.gov/pubmed/26687007).
18. Quick, Darren (February 3, 2016)."Clearing out damaged cells in mice extends lifespan by up to 35 percent"
(http://
www.gizmag.com/senescent-cell-mice-extend-lifespan/41659). www.gizmag.com. Retrieved 2016-02-04.
19. Regalado, Antonio (February 3, 2016)."In New Anti-Aging Strategy, Clearing Out Old Cells Increases Life Span of
Mice by 25 Percent" (https://www.technologyreview.com/s/600705/in-new-anti-aging-strategy-clearing-out-old-
cells-i
ncreases-life-span-of-mice-by-25-percent/#/set/id/600713/)
. MIT Technology Review. Retrieved 2016-02-04.
20. Shahini A, Choudhury D, Asmani M, Zhao R, Lei ,PAndreadis S (Jan 2018). "NANOG restores the impaired
myogenic differentiation potential of skeletal myoblasts after multiple population doublings".Stem Cell Research. 26:
55–66. doi:10.1016/j.scr.2017.11.018 (https://doi.org/10.1016%2Fj.scr.2017.11.018). PMID 29245050 (https://www.n
cbi.nlm.nih.gov/pubmed/29245050).
21. Shahini A, Mistriotis P, Asmani M, Zhao R, Andreadis S (Jun 2017)."NANOG Restores Contractility of Mesenchymal
Stem Cell-Based Senescent Microtissues"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467120). Tissue Eng
Part A. 23 (11–12): 535–545. doi:10.1089/ten.TEA.2016.0494(https://doi.org/10.1089%2Ften.TEA.2016.0494) .
PMC 5467120 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467120). PMID 28125933 (https://www.ncbi.nlm.nih.
gov/pubmed/28125933).
22. Mistriotis P, Bajpai V, Wang X, Rong N, Shahini A, Asmani M, Liang M, W ang J, Lei P, Liu S, Zhao R, Andreadis S
(Jan 2017). "NANOG Reverses the Myogenic Dif ferentiation Potential of Senescent Stem Cells by Restoring ACTIN
Filamentous Organization and SRF-Dependent Gene Expression".Stem Cells. 35 (1): 207–221.
doi:10.1002/stem.2452 (https://doi.org/10.1002%2Fstem.2452). PMID 27350449 (https://www.ncbi.nlm.nih.gov/pubm
ed/27350449).
23. Han J, Mistriotis P, Lei P, Wang D, Liu S, Zhao R, Andreadis S (Dec 2012)."Nanog Reverses the Effects of
Organismal Aging on Mesenchymal Stem Cell Proliferation and Myogenic Dif ferentiation Potential" (https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC3508087). Stem Cells. 30 (12): 2746–2759. doi:10.1002/stem.1223 (https://doi.org/10.
1002%2Fstem.1223). PMC 3508087 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508087). PMID 22949105 (htt
ps://www.ncbi.nlm.nih.gov/pubmed/22949105).
24. Munst B, Thier M, Winnemoller D, Helfen M, Thummer R, Edenhofer F (Jan 2016). "Nanog induces suppression of
senescence through downregulation of p27KIP1 expression"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC481331
2). Journal of Cell Science. 129 (5): 912–20. doi:10.1242/jcs.167932 (https://doi.org/10.1242%2Fjcs.167932).
PMC 4813312 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813312). PMID 26795560 (https://www.ncbi.nlm.nih.
gov/pubmed/26795560).
25. Burton; Faragher (2015). "Cellular senescence: from growth arrest to immunogenic conversion".
AGE. 37 (2).
doi:10.1007/s11357-015-9764-2(https://doi.org/10.1007%2Fs11357-015-9764-2) .
26. Campisi, Judith (February 2013)."Aging, Cellular Senescence, and Cancer"(https://www.ncbi.nlm.nih.gov/pmc/articl
es/PMC4166529). Annual Review of Physiology. 75: 685–705. doi:10.1146/annurev-physiol-030212-183653(https://
doi.org/10.1146%2Fannurev-physiol-030212-183653) . PMC 4166529 (https://www.ncbi.nlm.nih.gov/pmc/articles/PM
C4166529). PMID 23140366 (https://www.ncbi.nlm.nih.gov/pubmed/23140366).
27. Rodier, F.; Campisi, J. (14 February 2011)."Four faces of cellular senescence"(https://www.ncbi.nlm.nih.gov/pmc/art
icles/PMC3044123). The Journal of Cell Biology. 192 (4): 547–556. doi:10.1083/jcb.201009094(https://doi.org/10.10
83%2Fjcb.201009094). PMC 3044123 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044123).
28. Burton, Dominick G. A.; Krizhanovsky, Valery (31 July 2014). "Physiological and pathologi
cal consequences of
cellular senescence". Cellular and Molecular Life Sciences. 71 (22): 4373–4386. doi:10.1007/s00018-014-1691-3(ht
tps://doi.org/10.1007%2Fs00018-014-1691-3) .
29. Stephens C (April 2005)."Senescence: even bacteria get old"(http://linkinghub.elsevier.com/retrieve/pii/S0960-9822
(05)00377-5). Curr. Biol. 15 (8): R308–10. doi:10.1016/j.cub.2005.04.006(https://doi.org/10.1016%2Fj.cub.2005.04.
006). PMID 15854899 (https://www.ncbi.nlm.nih.gov/pubmed/15854899).
30. Hanahan D; Weinberg RA (January 2000). "The hallmarks of cancer".Cell. 100 (1): 57–70. doi:10.1016/S0092-
8674(00)81683-9 (https://doi.org/10.1016%2FS0092-8674%2800%2981683-9) . PMID 10647931 (https://www.ncbi.nl
m.nih.gov/pubmed/10647931).
31. Pearl, Raymond (1928).The Rate of Living, Being an Account of Some Experimental Studies on the Biology of Life
Duration. New York: Alfred A. Knopf.
32. 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(https://doi.org/10.1023%2FB%3ABGEN.0000038022.65024.d8) .
PMID 15314271 (https://www.ncbi.nlm.nih.gov/pubmed/15314271).
33. de Magalhães JP; Costa J; Church GM (1 February 2007)."An Analysis of the Relationship Between Metabolism,
Developmental Schedules, and Longevity Using Phylogenetic Independent Contrasts" (https://web.archive.org/web/2
0141223015347/http://biomedgerontology .oxfordjournals.org/content/62/2/149.long). The Journals of Gerontology
Series A: Biological Sciences and Medical Sciences . 62 (2): 149–60. doi:10.1093/gerona/62.2.149(https://doi.org/1
0.1093%2Fgerona%2F62.2.149). PMC 2288695 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2288695).
PMID 17339640 (https://www.ncbi.nlm.nih.gov/pubmed/17339640). Archived from the original (http://biomedgerontol
ogy.oxfordjournals.org/content/62/2/149.long) on 23 December 2014.
34. Speakman JR; Selman C; McLaren JS; Harper EJ (1 June 2002)."Living fast, dying when? The link between aging
and energetics" (http://jn.nutrition.org/content/132/6/1583S.long)
. The Journal of Nutrition. 132 (6 Suppl 2): 1583S–
97S. PMID 12042467 (https://www.ncbi.nlm.nih.gov/pubmed/12042467).
35. Freedman ND; Park Y; Abnet CC; Hollenbeck AR; Sinha R (May 2012)."Association of coffee drinking with total and
cause-specific mortality"(http://www.nejm.org/doi/full/10.1056/NEJMoa1112010). N. Engl. J. Med. 366 (20): 1891–
904. doi:10.1056/NEJMoa1112010(https://doi.org/10.1056%2FNEJMoa1112010) . PMC 3439152 (https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC3439152). PMID 22591295 (https://www.ncbi.nlm.nih.gov/pubmed/22591295).
36. Yang Y; Chan SW; Hu M; Walden R; Tomlinson B (2011). "Effects of some common food constituents on
cardiovascular disease"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262529). ISRN Cardiol. 2011: 397136.
doi:10.5402/2011/397136 (https://doi.org/10.5402%2F2011%2F397136) . PMC 3262529 (https://www.ncbi.nlm.nih.go
v/pmc/articles/PMC3262529). PMID 22347642 (https://www.ncbi.nlm.nih.gov/pubmed/22347642).
37. Spencer RL; Hutchison KE (1999)."Alcohol, aging, and the stress response"(http://pubs.niaaa.nih.gov/publications/
arh23-4/272-283.pdf) (PDF). Alcohol Research & Health. 23 (4): 272–83. PMID 10890824 (https://www.ncbi.nlm.nih.
gov/pubmed/10890824).
38. George T. Baker, III and Richard L. Sprott (1988). "Biomarkers of aging".EXPERIMENTAL GERONTOLOGY. 23 (4–
5): 223–239. doi:10.1016/0531-5565(88)90025-3(https://doi.org/10.1016%2F0531-5565%2888%2990025-3) .
PMID 3058488 (https://www.ncbi.nlm.nih.gov/pubmed/3058488).
39. Van Neste D, Tobin DJ (2004). "Hair cycle and hair pigmentation: dynamic interactions an
d changes associated with
aging". MICRON. 35 (3): 193–200. doi:10.1016/j.micron.2003.11.006(https://doi.org/10.1016%2Fj.micron.2003.11.0
06). PMID 15036274 (https://www.ncbi.nlm.nih.gov/pubmed/15036274).
40. Miller RA (2001). "Biomarkers of aging: prediction of longevity by using age-sensitive-cell
T subset determinations in
a middle-aged, genetically heterogeneous mouse population".JOURNALS OF GERONTOLOGY. 56 (4): B180–
B186. doi:10.1093/gerona/56.4.b180(https://doi.org/10.1093%2Fgerona%2F56.4.b180) . PMID 11283189 (https://w
ww.ncbi.nlm.nih.gov/pubmed/11283189).
41. Horvath S (2013). "DNA methylation age of human tissues and cell types"(http://genomebiology.com/2013/14/10/r11
5). Genome Biology. 14 (10): R115. doi:10.1186/gb-2013-14-10-r115(https://doi.org/10.1186%2Fgb-2013-14-10-r11
5). PMC 4015143 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015143). PMID 24138928 (https://www.ncbi.nlm.
nih.gov/pubmed/24138928).
42. Zhavoronkov A (2016)."Deep biomarkers of human aging: Application of deep neural networks to biomarker
development" (http://www.aging-us.com/article/SzdNR3HCatAdyvwPR/text). Aging. 8 (5): 1021.
doi:10.18632/aging.100968(https://doi.org/10.18632%2Faging.100968). PMC 4931851 (https://www.ncbi.nlm.nih.go
v/pmc/articles/PMC4931851). PMID 27191382 (https://www.ncbi.nlm.nih.gov/pubmed/27191382).
43. Peters M (2015). "The transcriptional landscape of age in human peripheral blood"(http://www.nature.com/articles/n
comms9570).
44. 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 (https://doi.org/10.1002%2Fyea.1412).
PMID 17083143 (https://www.ncbi.nlm.nih.gov/pubmed/17083143).
45. Mounkes LC; Kozlov S (2003)."A progeroid syndrome in mice is caused by defects in A-type lamins"(http://www.nat
ure.com.gate2.inist.fr/nature/journal/v423/n6937/pdf/nature01631.pdf)(PDF). Nature. 423 (6937): 298–301.
doi:10.1038/nature01631 (https://doi.org/10.1038%2Fnature01631). PMID 12748643 (https://www.ncbi.nlm.nih.gov/p
ubmed/12748643).

External links
Senescence at Curlie (based on DMOZ)
Jones, Owen R.; Scheuerlein, Alexander; Salguero-Gómez, Roberto; Camarda, Carlo Giovanni; Schaible, Ralf;
Casper, Brenda B.; Dahlgren, Johan P.; Ehrlén, Johan; García, María B.; Menges, Eric S.; Quintana-Ascencio, Pedro
F.; Caswell, Hal; Baudisch, Annette; Vaupel, James W. (2013). "Diversity of ageing across the tree of life".Nature.
505 (7482): 169–173. doi:10.1038/nature12789. Lay summary – National Geographic (8 December 2013).

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