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Biogerontology

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The hand of an older adult
Life expectancy in various countries of the world in 2019

Biogerontologyis the sub-field ofgerontologyconcerned with thebiological aging process,its evolutionary origins, and potential means to intervene in the process. The term "biogerontology" was coined byS. Rattan,and came in regular use with the start of the journalBiogerontologyin 2000. It involves interdisciplinary research on the causes, effects, and mechanisms of biological aging. BiogerontologistLeonard Hayflickhas said that the natural average lifespan for a human is around 92 years and, if humans do not invent new approaches to treat aging, they will be stuck with this lifespan.[1]James Vaupelhas predicted thatlife expectancyin industrialized countries will reach 100 for children born after the year 2000.[2]Many surveyed biogerontologists have predicted life expectancies of more than three centuries for people born after the year 2100.[3]Other scientists, more controversially, suggest the possibility of unlimited lifespans for those currently living. For example,Aubrey de Greyoffers the "tentative timeframe" that with adequate funding of research to develop interventions in aging such asstrategies for engineered negligible senescence,"we have a 50/50 chance of developing technology within about 25 to 30 years from now that will, under reasonable assumptions about the rate of subsequent improvements in that technology, allow us to stop people from dying of aging at any age".[4]The idea of this approach is to use presently available technology to extend lifespans of currently living humans long enough for future technological progress to resolve any remaining aging-related issues. This concept has been referred to aslongevity escape velocity.

Biomedical gerontology,also known as experimental gerontology and life extension, is a sub-discipline of biogerontology endeavoring to slow, prevent, and even reverse aging in both humans and animals.

Approaches to aging[edit]

Wrinkled skin on the face is a characteristic feature of old people.

Biogerontologists vary in the degree to which they focus on the study of the aging process as a means of mitigating thediseases of aging,or as a method for extending lifespan. A relatively new interdisciplinary field called geroscience focuses on preventing diseases of aging and prolonging the 'healthspan' over which an individual lives without serious illness.[5][6][7]The approach of biogerontologists is that aging isdiseaseper seand should be treated directly, with the ultimate goal of having the probability of individual dying be independent of their age (if external factors are held constant).[8][9][10]This is in contrast to the opinion thatmaximum life spancan not, or should not, be altered.

Biogerontology should not be confused withgeriatrics,which is a field of medicine that studying the treatment of existing disease in aging people, rather than the treatment of aging itself.

There are numerous theories of aging, and no one theory has been entirely accepted. At their extremes, the wide spectrum of aging theories can be categorized into programmed theories – which imply that aging follows a biological timetable, and error theories – which suggest aging occurs due to cumulative damage experienced by organisms.[11]

Stochastic theories[edit]

Stochastic theories of aging are theories suggesting that aging is caused by small changes in the body over time and the body's failure to restore the system and mend the damages to the body. Cells and tissues are injured due to the accumulation of damage over time resulting in the diminished functioning of organs. The notion of accumulated damage was first introduced in 1882 by biologistDr. August Weismannas the "wear and tear" theory.[12][13]

Wear and tear theories[edit]

Wear and tear theories of aging began to be introduced yet in 19th century.[13]They suggest that as an individual ages, body parts such as cells and organs wear out from continued use. Wearing of the body can be attributable to internal or external causes that eventually lead to an accumulation ofinsultswhich surpasses the capacity for repair. Due to these internal and external insults, cells lose their ability to regenerate, which ultimately leads to mechanical and chemical exhaustion. Some insults include chemicals in the air, food, or smoke. Other insults may be things such as viruses, trauma, free radicals,cross-linking,and high body temperature.[14]

Accumulation[edit]

Accumulation theories of aging suggest that aging is bodily decline that results from an accumulation of elements, whether introduced to the body from the environment or resulting from cellmetabolism.[14]

Mutation accumulation theory[edit]

Main article:Mutation accumulation theory

Mutation accumulation theory was first proposed byPeter Medawarin 1952[12]as an evolutionary explanation for biological ageing and the associated decline in fitness that accompanies it.[15]The theory explains that, in the case where harmfulmutationsare only expressed later in life, when reproduction has ceased and future survival is increasingly unlikely, then these mutations are likely to be unknowingly passed on to future generations.[16]In this situation the force ofnatural selectionwill be weak, and so insufficient to consistently eliminate these mutations. Medawar posited that over time these mutations would accumulate due togenetic driftand lead to the evolution of what is now referred to as ageing.

Free radical theory[edit]

Main article:Free-radical theory of aging

Free radicalsare reactive molecules produced by cellular and environmental processes, and can damage the elements of the cell such as thecell membraneandDNAand cause irreversible damage. The free-radical theory of aging proposes that this damage cumulatively degrades the biological function of cells and impacts the process of aging.[17]The idea that free radicals are toxic agents was first proposed byRebeca Gerschmanand colleagues in 1945,[18]but came to prominence in 1956, whenDenham Harmanproposed the free-radical theory of aging and even demonstrated that free radical reactions contribute to the degradation of biological systems.[19]Oxidative damage of many types accumulate with age, such as oxidative stress that oxygen-free radicals,[20]because the free radical theory of aging argues that aging results from the damage generated byreactive oxygen species(ROS).[21]ROS are small, highly reactive, oxygen-containing molecules that can damage a complex of cellular components such as fat, proteins, or from DNA; they are naturally generated in small amounts during the body's metabolic reactions. These conditions become more common as humans grow older and include diseases related to aging, such as dementia, cancer and heart disease. Amount of free radicals in the cell can be reduced with help ofantioxidants.But there's a problem that some free radicals are used by organism as signal molecules, and too active general reduction of free radicals causes to organism more harm than good. Some time ago[when?]idea of slowing aging using antioxidants were very popular but now high doses of antioxidants are considered harmful. At present[when?]some scientists try to invent approaches of local suppression of free radicals only in certain places of cells.[22][23]Efficiency of such approach remains to be unclear, research is ongoing.

DNA damage theories[edit]

Main article:DNA damage theory of aging

DNA damagehas been one of the major causes in diseases related to aging. The stability of thegenomeis defined by the cells machinery of repair, damage tolerance, and checkpoint pathways that counteracts DNA damage. One hypothesis proposed by physicistGioacchino Faillain 1958 is that damage accumulation to the DNA causes aging.[24]The hypothesis was developed soon by physicistLeó Szilárd.[25]This theory has changed over the years as new research has discovered new types of DNA damage and mutations, and several theories of aging argue that DNA damage with or without mutations causes aging.[26][27]

DNA damage is distinctly different frommutation,although both are types of error inDNA.DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of standard base pairs. The theory that DNA damage is the primary cause of aging is based, in part, on evidence in human and mouse that inherited deficiencies in DNA repair genes often cause accelerated aging.[28][29][26]There is also substantial evidence that DNA damage accumulates with age in mammalian tissues, such as those of the brain, muscle, liver and kidney (seeDNA damage theory of agingandDNA damage (naturally occurring)). One expectation of the theory (that DNA damage is the primary cause of aging) is that among species with differing maximum life spans, the capacity to repair DNA damage should correlate with lifespan. The first experimental test of this idea was by Hart and Setlow[30]who measured the capacity of cells from seven different mammalian species to carry out DNA repair. They found that nucleotide excision repair capability increased systematically with species longevity. This correlation was striking and stimulated a series of 11 additional experiments in different laboratories over succeeding years on the relationship of nucleotide excision repair and life span in mammalian species (reviewed by Bernstein and Bernstein[31]). In general, the findings of these studies indicated a good correlation between nucleotide excision repair capacity and life span. Further support for the theory that DNA damage is the primary cause of aging comes from study ofPoly ADP ribose polymerases(PARPs). PARPs are enzymes that are activated by DNA strand breaks and play a role in DNA base excision repair. Burkle et al. reviewed evidence that PARPs, and especially PARP-1, are involved in maintaining mammalian longevity.[32]The life span of 13 mammalian species correlated with poly(ADP ribosyl)ation capability measured in mononuclear cells. Furthermore, lymphoblastoid cell lines from peripheral blood lymphocytes of humans over age 100 had a significantly higher poly(ADP-ribosyl)ation capability than control cell lines from younger individuals.

Cross-linking theory[edit]

The cross-linking theory proposes thatadvanced glycation end-products(stable bonds formed by the binding of glucose to proteins) and other aberrantcross-linksaccumulating in aging tissues is the cause of aging. The crosslinking of proteins disables their biological functions. The hardening of theconnective tissue,kidney diseases, andenlargement of the heartare connected to the cross-linking of proteins.Crosslinking of DNAcan inducereplicationerrors, and this leads to deformed cells and increases the risk ofcancer.[12]

Stem cell theory of aging[edit]

Main article:Stem cell theory of aging

Genetic[edit]

Genetic theories of aging propose that aging is programmed within each individual's genes. According to this theory, genes dictate cellular longevity. Programmed cell death, orapoptosis,is determined by a "biological clock" via genetic information in the nucleus of the cell. Genes responsible for apoptosis provide an explanation for cell death, but are less applicable to death of an entire organism. An increase in cellular apoptosis may correlate to aging, but is not a 'cause of death'. Environmental factors and genetic mutations can influence gene expression and accelerate aging.

More recentlyepigeneticshave been explored as a contributing factor. Theepigenetic clock,which relatively objectively measures the biological age of cells, are useful tool for testing different anti-aging approaches.[33]The most famous epigenetic clock is Horvath's clock, but now already more accurate analogues have appeared.

General imbalance[edit]

General imbalance theories of aging suggest that body systems, such as theendocrine,nervous,andimmune systems,gradually decline and ultimately fail to function. The rate of failure varies system by system.[14]

Immunological theory[edit]

The immunological theory of aging suggests that the immune system weakens as an organism ages. This makes the organism unable to fight infections and less able to destroy old andneoplastic cells.This leads to aging and will eventually lead to death. This theory of aging was developed byRoy Walfordin 1969. According to Walford, incorrect immunological procedures are the cause of the process of aging.[17]Walford, who stated that his optimized health regime would allow him to live to 120, died ofamytrophic lateral sclerosisat age 79.

See also[edit]

References[edit]

  1. ^Geoff Watts (June 2011)."Leonard Hayflick and the limits of aging".The Lancet.377(9783): 2075.doi:10.1016/S0140-6736(11)60908-2.PMID21684371.S2CID205963134.
  2. ^Christensen, L; Doblhammer, K; Rau, G; Vaupel, JW (2009)."Aging populations: the challenges ahead".The Lancet.374(9696): 1196–1208.doi:10.1016/s0140-6736(09)61460-4.PMC2810516.PMID19801098.
  3. ^Richel, Theo (December 2003)."Will human life expectancy quadruple in the next hundred years? Sixty gerontologists say public debate on life extension is necessary".Journal of Anti-Aging Medicine.6(4): 309–314.doi:10.1089/109454503323028902.PMID15142432.
  4. ^de Grey, Aubrey D. N. J.;Rae, Michael (October 14, 2008).Ending Aging.St. Martin's Griffin. p. 15.ISBN978-0-312-36707-7.
  5. ^Lithgow, Gordon J. (1 September 2013)."Origins of Geroscience".Public Policy & Aging Report.4(1): 10–11.doi:10.1093/ppar/23.4.10.
  6. ^Burch, John B.; et al. (2014-05-08)."Advances in Geroscience: Impact on Healthspan and Chronic Disease".The Journals of Gerontology: Series A.69(Suppl_1): S1–S3.doi:10.1093/gerona/glu041.PMC4036419.PMID24833579.
  7. ^Seals, Douglas R.; Justice, Jamie N.; LaRocca, Thomas J. (2015-01-29)."Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity".The Journal of Physiology.594(8): 2001–2024.doi:10.1113/jphysiol.2014.282665.PMC4933122.PMID25639909.
  8. ^Stambler, Ilia (2017-10-01)."Recognizing Degenerative Aging as a Treatable Medical Condition: Methodology and Policy".Aging and Disease.8(5): 583–589.doi:10.14336/AD.2017.0130.PMC5614323.PMID28966803.
  9. ^The Lancet Diabetes & Endocrinology (2018-08-01)."Opening the door to treating ageing as a disease".The Lancet Diabetes & Endocrinology.6(8): 587.doi:10.1016/S2213-8587(18)30214-6.PMID30053981.S2CID51726070.
  10. ^Khaltourina, Daria;Matveyev, Yuri; Alekseev, Aleksey; Cortese, Franco; Ioviţă, Anca (July 2020)."Aging Fits the Disease Criteria of the International Classification of Diseases".Mechanisms of Ageing and Development.189:111230.doi:10.1016/j.mad.2020.111230.PMID32251691.S2CID214779653.
  11. ^Carlos López-Otín; Maria A. Blasco; Linda Partridge; Manuel Serrano; Guido Kroemer (2013-06-06)."The Hallmarks of Aging".Cell.153(6): 1194–1217.doi:10.1016/j.cell.2013.05.039.PMC3836174.PMID23746838.
  12. ^abcLipsky, Martin S.; King, Mitch (2015). "Biological theories of aging".Disease-a-Month.61(11): 460–466.doi:10.1016/j.disamonth.2015.09.005.PMID26490576.
  13. ^abJessica Kelly."Wear-and-Tear Theory".Lumen Learning.
  14. ^abcTaylor, Albert W.; Johnson, Michel J. (2008).Physiology of Exercise and Healthy Aging.Human Kinetics.ISBN978-0-7360-5838-4.
  15. ^Medawar, Peter Brian (1952).An unsolved problem of Biology.London:H. K. Lewis & Co. Ltd.Lewis.
  16. ^Fabian, Daniel (2011). "The Evolution of Aging".Nature Education Knowledge.3:1–10.
  17. ^abBoniewska-Bernacka, Ewa (2016)."Selected Theories of Aging"(PDF).Higher School's Pulse.10:36–39.
  18. ^Gerschman R, Gilbert DL, Nye SW, Dwyer P, Fenn WO (7 May 1954). "Oxygen poisoning and x-irradiation: a mechanism in common".Science.119(3097): 623–626.Bibcode:1954Sci...119..623G.doi:10.1126/science.119.3097.623.PMID13156638.S2CID27600003.
  19. ^Harman, D (November 1981)."The aging process".Proc. Natl. Acad. Sci. U.S.A.78(11): 7124–7128.Bibcode:1981PNAS...78.7124H.doi:10.1073/pnas.78.11.7124.PMC349208.PMID6947277.
  20. ^Hagen, Bruce N; MK Shigenaga; TM Hagen (September 1993)."Oxidants, antioxidants, and the degenerative diseases of aging".Proc. Natl. Acad. Sci. U.S.A.90(17): 7915–7922.Bibcode:1993PNAS...90.7915A.doi:10.1073/pnas.90.17.7915.PMC47258.PMID8367443.
  21. ^Beckman, KB; Ames BN (April 1998). "The free radial theory of aging matures".Physiol Rev.78(2): 547–581.doi:10.1152/physrev.1998.78.2.547.PMID9562038.S2CID1774858.
  22. ^"SKQ Project | Molecule".Mitotech.Retrieved17 April2021.
  23. ^"Митохондриально-направленные антиоксиданты против старения"[Mitochondrial-targeted anti-aging antioxidants] (in Russian). SKQ Project. 11 December 2018.
  24. ^Failla, G (30 September 1958). "The aging process and cancerogenesis".Annals of the New York Academy of Sciences.71(6): 1124–1140.Bibcode:1958NYASA..71.1124F.doi:10.1111/j.1749-6632.1958.tb54674.x.PMID13583876.
  25. ^Szilard, Leo (January 1959)."On the nature of the aging process".Proc. Natl. Acad. Sci. U.S.A.45(1): 30–45.Bibcode:1959PNAS...45...30S.doi:10.1073/pnas.45.1.30.PMC222509.PMID16590351.
  26. ^abFreitas, AA; de Magalhaes, JP (Jul–Oct 2011). "A review and appraisal of the DNA damage theory of aging".Mutat Res.728(1–2): 12–22.doi:10.1016/j.mrrev.2011.05.001.PMID21600302.
  27. ^Gensler, H. L.; Bernstein, H. (September 1981). "DNA damage as the primary cause of aging". Q Rev Biol. 56 (3): 279–303.doi:10.1086/412317.PMID7031747.S2CID20822805
  28. ^Hoeijmakers JH (October 2009). "DNA damage, aging, and cancer".The New England Journal of Medicine.361(15): 1475–1485.doi:10.1056/NEJMra0804615.PMID19812404.
  29. ^Diderich K, Alanazi M, Hoeijmakers JH (July 2011)."Premature aging and cancer in nucleotide excision repair-disorders".DNA Repair.10(7): 772–780.doi:10.1016/j.dnarep.2011.04.025.PMC4128095.PMID21680258.
  30. ^Hart RW, Setlow RB (June 1974)."Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species".Proceedings of the National Academy of Sciences of the United States of America.71(6): 2169–2173.Bibcode:1974PNAS...71.2169H.doi:10.1073/pnas.71.6.2169.PMC388412.PMID4526202.
  31. ^Bernstein C, Bernstein H (1991).Aging, Sex, and DNA Repair.San Diego: Academic Press.ISBN978-0-12-092860-6.
  32. ^Bürkle A, Brabeck C, Diefenbach J, Beneke S (May 2005). "The emerging role of poly(ADP-ribose) polymerase-1 in longevity".The International Journal of Biochemistry & Cell Biology.37(5): 1043–1053.doi:10.1016/j.biocel.2004.10.006.PMID15743677.
  33. ^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.PMC4015143.PMID24138928.(Erratum:doi:10.1186/s13059-015-0649-6,PMID25968125,Retraction Watch.If theerratumhas been checked and does not affect the cited material, please replace{{erratum|...}}with{{erratum|...|checked=yes}}.)

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