Editing Senescence (section)

====Chemical damage====
{{See also|DNA damage theory of aging}}
[[Image:Edward S. Curtis Collection People 086.jpg|thumb|upright=.8|Elderly [[Klamath people|Klamath]] woman photographed by [[Edward S. Curtis]] in 1924]]
One of the earliest aging theories was the ''[[Rate-of-living theory|Rate of Living Hypothesis]]'' described by [[Raymond Pearl]] in 1928<ref>{{Cite book| vauthors = Pearl R |title=The Rate of Living, Being an Account of Some Experimental Studies on the Biology of Life Duration|publisher=Alfred A. Knopf|year=1928|location=New York|lccn=28000834}}{{Page needed|date=September 2010}}</ref> (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. [[Calorie restriction|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|date=March 2009}} 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.<ref>{{cite journal | vauthors = Brunet-Rossinni AK, Austad SN | title = Ageing studies on bats: a review | journal = Biogerontology | volume = 5 | issue = 4 | pages = 211–22 | year = 2004 | pmid = 15314271 | doi = 10.1023/B:BGEN.0000038022.65024.d8 | s2cid = 22755811 }}</ref> In a 2007 analysis it was shown that, when modern statistical methods for correcting for the effects of body size and [[Phylogenetic tree|phylogeny]] are employed, metabolic rate does not correlate with [[longevity]] in mammals or birds.<ref>{{cite journal | vauthors = de Magalhães JP, Costa J, Church GM | title = An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 62 | issue = 2 | pages = 149–60 | date = February 2007 | pmid = 17339640 | pmc = 2288695 | doi = 10.1093/gerona/62.2.149 | citeseerx = 10.1.1.596.2815 }}</ref>

With respect to specific types of chemical damage caused by metabolism, it is suggested that damage to long-lived [[biopolymer]]s, such as structural [[protein]]s or [[DNA damage theory of aging|DNA]], caused by ubiquitous chemical agents in the body such as [[oxygen]] and [[sugar]]s, are in part responsible for aging. The damage can include breakage of biopolymer chains, [[cross-link]]ing of biopolymers, or chemical attachment of unnatural substituents ([[hapten]]s) to biopolymers.{{citation needed|date=December 2019}}
Under normal [[wikt:aerobic|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 (chemistry)|radical]] and eventually other reactive species including other [[peroxide]]s and [[singlet oxygen]], which can, in turn, generate [[radical (chemistry)|free radical]]s capable of damaging structural proteins and DNA.<ref name="pmid1383772" /> Certain metal [[ion]]s found in the body, such as [[copper]] and [[iron]], may participate in the process. (In [[Wilson's disease]], a [[genetic disorder|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]] [[antioxidant]]s, for example in [[coffee]],<ref>{{cite journal | vauthors = Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R | title = Association of coffee drinking with total and cause-specific mortality | journal = The New England Journal of Medicine | volume = 366 | issue = 20 | pages = 1891–904 | date = May 2012 | pmid = 22591295 | pmc = 3439152 | doi = 10.1056/NEJMoa1112010 }}</ref> and [[green tea|tea]].<ref>{{cite journal | vauthors = Yang Y, Chan SW, Hu M, Walden R, Tomlinson B | title = Effects of some common food constituents on cardiovascular disease | journal = ISRN Cardiology | volume = 2011 | pages = 397136 | year = 2011 | pmid = 22347642 | pmc = 3262529 | doi = 10.5402/2011/397136 | doi-access = free }}</ref> However their typically positive effects on lifespans when consumption is moderate<ref>{{cite journal |last1=Poole |first1=Robin |last2=Kennedy |first2=Oliver J. |last3=Roderick |first3=Paul |last4=Fallowfield |first4=Jonathan A. |last5=Hayes |first5=Peter C. |last6=Parkes |first6=Julie |title=Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes |journal=BMJ |date=22 November 2017 |volume=359 |pages=j5024 |doi=10.1136/bmj.j5024 |pmid=29167102 |pmc=5696634 }}</ref><ref>{{cite journal |last1=O'Keefe |first1=James H. |last2=DiNicolantonio |first2=James J. |last3=Lavie |first3=Carl J. |title=Coffee for Cardioprotection and Longevity |journal=Progress in Cardiovascular Diseases |date=1 May 2018 |volume=61 |issue=1 |pages=38–42 |doi=10.1016/j.pcad.2018.02.002 |pmid=29474816 }}</ref><ref>{{cite journal |last1=Grosso |first1=Giuseppe |last2=Godos |first2=Justyna |last3=Galvano |first3=Fabio |last4=Giovannucci |first4=Edward L. |title=Coffee, Caffeine, and Health Outcomes: An Umbrella Review |journal=Annual Review of Nutrition |date=21 August 2017 |volume=37 |issue=1 |pages=131–156 |doi=10.1146/annurev-nutr-071816-064941 |pmid=28826374 }}</ref> have also been explained by effects on [[autophagy]],<ref>{{cite journal |last1=Dirks-Naylor |first1=Amie J. |title=The benefits of coffee on skeletal muscle |journal=Life Sciences |date=15 December 2015 |volume=143 |pages=182–6 |doi=10.1016/j.lfs.2015.11.005 |pmid=26546720 }}</ref> [[glucose metabolism]]<ref>{{cite journal |last1=Reis |first1=Caio E. G. |last2=Dórea |first2=José G. |last3=da Costa |first3=Teresa H. M. |title=Effects of coffee consumption on glucose metabolism: A systematic review of clinical trials |journal=Journal of Traditional and Complementary Medicine |date=1 July 2019 |volume=9 |issue=3 |pages=184–191 |doi=10.1016/j.jtcme.2018.01.001 |pmid=31193893 |pmc=6544578 }}</ref> and [[AMP-activated protein kinase|AMPK]].<ref>{{cite journal |last1=Loureiro |first1=Laís Monteiro Rodrigues |last2=Reis |first2=Caio Eduardo Gonçalves |last3=Costa |first3=Teresa Helena Macedo da |title=Effects of Coffee Components on Muscle Glycogen Recovery: A Systematic Review |journal=International Journal of Sport Nutrition and Exercise Metabolism |date=1 May 2018 |volume=28 |issue=3 |pages=284–293 |doi=10.1123/ijsnem.2017-0342 |pmid=29345166 }}</ref>

[[Sugar]]s such as [[glucose]] and [[fructose]] can react with certain [[amino acid]]s 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 ''[[Advanced glycation endproduct|glycoxidation]]''.

[[Reactive oxygen species|Free radicals]] can damage proteins, [[lipid]]s or [[DNA damage theory of aging|DNA]]. [[Glycation]] mainly damages proteins. Damaged proteins and lipids accumulate in [[lysosome]]s 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 [[enzyme]]s reduces cellular functionality. Lipid [[redox|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 disease]]s" are due to defective [[DNA repair]] enzymes.<ref name="KimuraSuzuki2008">{{cite book|vauthors=Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K|url=https://books.google.com/books?id=arjZMwAACAAJ&pg=PA1|title=New Research on DNA Damage|publisher=Nova Science Publishers|year=2008|isbn=978-1604565812|veditors=Kimura H, Suzuki A|pages=1–47|chapter=Cancer and aging as consequences of un-repaired DNA damage.|chapter-url=https://www.novapublishers.com/catalog/product_info.php?products_id=43247|access-date=4 February 2016|archive-date=15 November 2023|archive-url=https://web.archive.org/web/20231115062953/https://books.google.com/books?id=arjZMwAACAAJ&pg=PA1|url-status=live}}</ref><ref name="pmid27164092">{{cite journal | vauthors = Pan MR, Li K, Lin SY, Hung WC | title = Connecting the Dots: From DNA Damage and Repair to Aging | journal = International Journal of Molecular Sciences | volume = 17 | issue = 5 | pages = 685 | date = May 2016 | pmid = 27164092 | pmc = 4881511 | doi = 10.3390/ijms17050685 | doi-access = free }}</ref>

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.<ref>{{cite journal | vauthors = Spencer RL, Hutchison KE | title = Alcohol, aging, and the stress response | journal = Alcohol Research & Health | volume = 23 | issue = 4 | pages = 272–83 | year = 1999 | pmid = 10890824 | pmc = 6760387 | url = http://pubs.niaaa.nih.gov/publications/arh23-4/272-283.pdf | access-date = 8 April 2008 | archive-date = 11 December 2018 | archive-url = https://web.archive.org/web/20181211163358/http://pubs.niaaa.nih.gov/publications/arh23-4/272-283.pdf | url-status = dead }}</ref>