Ageing Genes: Gerontogenes


The idea of gerontogenes is in line with the evolutionary explanation of ageing as being an emergent phenomenon as a result of the imperfect maintenance and repair systems. Although evolutionary processes did not select for any specific ageing genes that restrict and determine the lifespan of an individual, the term ‘gerontogenes’ primarily refers to any genes that may seem to influence ageing and longevity, without being specifically selected for that role. Such genes can also be called ‘virtual gerontogenes’ by virtue of their indirect influence on the rate and process of ageing. More than 1000 virtual gerontogenes have been associated with ageing and longevity in model organisms and humans. The ‘real’ genes, which do influence the essential lifespan of a species, and have been selected for in accordance with the evolutionary life history of the species, are known as the longevity assurance genes.

Key Concepts

  • Biological ageing is a progressive decline in functional ability and an increase in the chances of frailty, diseases and death.
  • Ageing can be considered to set in mainly after the completion of the essential lifespan (ELS) of a species.
  • ELS is the duration of time required by a species in its natural environment in order to grow, develop, mature and reproduce.
  • Evolution has selected for longevity assurance genes (LAG) that determine ELS of a species.
  • Genetic pathways of maintenance and repair are the basis of LAG, and give rise to the homeodynamic space of an individual within a species.
  • Ageing is the progressive shrinkage of the homeodynamic space.
  • Evolution has not selected for any genes with the specific function of causing ageing and terminating the life of an individual.
  • Ageing, age‐related diseases and death are not programmed.
  • Genes for ageing – gerontogenes – is a conceptual term for discussing the involvement of genes in affecting the rate and extent of ageing.
  • Gerontogenes are not real; they are, at best, virtual in the sense that LAG become altered because of molecular damage and epigenetic alterations.
  • Hundreds of putative virtual gerontogenes have been associated with the longevity of model organisms and humans.
  • Eliminating ageing and death by gene therapy is at present only a wishful thinking.

Keywords: ageing; homeostasis; homeodynamics; lifespan; longevity assurance

Figure 1. Homeodynamic space (HS) is the ability of all living systems, characterised by stress tolerance, damage control and constant remodelling. An apparently normal and healthy child is born with a certain basic level of HS (represented in green), but with a large ‘vulnerability zone’ (represented in red). During further growth, development and maturation, HS becomes enlarged, whereas the vulnerability zone becomes smaller. Continued survival beyond essential lifespan of the species allows the progressive accumulation of molecular damage as a result of the imperfections of the longevity assurance genes, and hence, the shrinkage of the HS as the phenotype of ageing. The increased vulnerability zone increases the chances of emergence of one or more age‐related diseases.


Barzilai N and Shuldiner AR (2001) Searching for human longevity genes: the future history of gerontology in the post‐genomic era. The Journals of Gerontology, Series A, Biological Sciences and Medical Sciences 56A: M83–M87.

Carnes BA, Olshansky SJ and Grahn D (2003) Biological evidence for limits to the duration of life. Biogerontology 4: 31–45.

Carnes BA (2007) Senescence viewed through the lens of comparative biology. Annals of the New York Academy of Sciences 1114: 14–22.

Carnes BA (2011) What is lifespan regulation and why does it exist? Biogerontology 12: 367–374.

Carnes BA and Witten TM (2013) How long must humans live? The Journals of Gerontology, Series A, Biological Sciences and Medical Sciences 69: 965–970. DOI: 10.1093/gerona/glt164.

Castillo‐Quan JI, Kinghorn KJ and Bjedov I (2015) Genetics and pharmacology of longevity: the road to therapeutics for healthy aging. Advances in Genetics 90: 1–101.

Dong X, Milholland B and Vijg J (2016) Evidence for a limit to human lifespan. Nature 538: 257–259.

Fontana L, Partridge L and Longo VD (2010) Extending healthy life span–from yeast to humans. Science 328: 321–326.

Goldstein S, Murano S and Shmookler‐Reis RJ (1990) Werner syndrome: a molecular genetic hypothesis. Journal of Gerontology 45: B3–B8.

Hayflick L (2007) Biological aging is no longer an unsolved problem. Annals of the New York Academy of Sciences 1100: 1–13.

Hipkiss AR (2001) On the “struggle between chemistry and biology during aging”– implications for DNA repair, apoptosis and proteolysis, and a novel route of intervention. Biogerontology 2: 173–178.

Holliday R (2006) Aging is no longer an unsolved problem in biology. Annals of the New York Academy of Sciences 1067: 1–9.

Holliday R (2007) Ageing: The Paradox of Life. Dordrecht, The Netherlands: Springer.

Holliday R (2009) Genes and the evolution of longevities. Biogerontology 10: 1–2.

Holliday R and Rattan SIS (2010) Longevity mutants do not establish any “new science” of ageing. Biogerontology 11: 507–511.

Jones DP (2015) Redox theory of aging. Redox Biology 5: 71–79.

Kapahi P, Boulton ME and Kirkwood TBL (1999) Positive correlation between mammalian life span and cellular resistance to stress. Free Radical Biology & Medicine 26: 495–500.

Kenyon CJ (2010) The genetics of ageing. Nature 464: 504–512.

Kipling D, Davis T, Ostler EL and Faragher RG (2004) What can progeroid syndromes tell us about human aging? Science 305: 1426–1431.

Kirkwood TBL, Holliday R and Rosenberger RF (1984) Stability of the cellular translation process. International Review of Cytology 92: 93–132.

Kirkwood TBL and Rose MR (1991) Evolution of senescence: late survival sacrificed for reproduction. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 332: 15–24.

Kowald A and Kirkwood TB (2016) Can aging be programmed? A critical literature review. Aging Cell 15: 986–998.

Kuningas M, Mooijaart SP, van Heemst D, et al. (2008) Genes encoding longevity: from model organisms to humans. Aging Cell 7: 270–280.

Levine ME and Crimmins EM (2016) A genetic network associated with stress resistance, longevity, and cancer in humans. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 71: 703–712.

Li Y and Schellhorn HE (2007) Can ageing‐related degenerative diseases be ameliorated through administration of vitamin C at pharmacological levels? Medical Hypotheses 68: 1315–1317.

de Magalhaes JP (2012) Programmatic features of aging originating in development: aging mechanisms beyond molecular damage? FASEB Journal 26: 4821–4826.

de Magalhaes JP (2014a) The scientific quest for lasting youth: prospects for curing aging. Rejuvenation Research 17: 458–467.

de Magalhaes JP (2014b) Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research. Cell Cycle 13: 2671–2673.

Martin GM (2007) Modalities of gene action predicted by the classical evolutionary theory of aging. Annals of the New York Academy of Sciences 1100: 14–20.

Martin GM, Bergman A and Barzilai N (2007) Genetic determinants of human health span and life span. PLoS Genetics 3: e125.

Mitnitski AB, Rutenberg AD, Farrell S and Rockwood K (2017) Aging, frailty and complex networks. Biogerontology 18: 433–446.

Park SH, Kang HJ, Kim HS, et al. (2011) Higher DNA repair activity is related with longer replicative life span in mammalian embryonic fibroblast cells. Biogerontology 12: 565–579.

Partridge L (2001) Evolutionary theories of ageing applied to long‐lived organisms. Experimental Gerontology 36: 641–650.

Perls T, Kunkel L and Puca A (2002) The genetics of aging. Current Opinion in Genetics & Development 12: 362–369.

Rattan SIS (1985) Beyond the present crisis in gerontology. BioEssays 2: 226–228.

Rattan SIS (1989) DNA damage and repair during cellular aging. International Review of Cytology 116: 47–88.

Rattan SIS (1995) Gerontogenes: real or virtual? FASEB Journal 9: 284–286.

Rattan SIS (2000) Biogerontology: the next step. Annals of the New York Academy of Sciences 908: 282–290.

Rattan SIS (2002) N6‐furfuryladenine (kinetin) as a potential anti‐aging molecule. Journal of Anti‐Aging Medicine 5: 113–116.

Rattan SIS (2006) Theories of biological aging: genes, proteins and free radicals. Free Radical Research 40: 1230–1238.

Rattan SIS (2008) Increased molecular damage and heterogeneity as the basis of aging. Biological Chemistry 389: 267–272.

Rattan SIS and Singh R (2009) Gene therapy in aging. Gene Therapy 16: 3–9.

Rattan SIS (2012) Biogerontology: from here to where? The Lord Cohen Medal Lecture‐2011. Biogerontology 13: 83–91.

Rattan SIS (2015) Biology of ageing: principles, challenges and perspectives. Romanian Journal of Morphology and Embryology 56: 1251–1253.

Samaras N, Papadopoulou MA, Samaras D and Ongaro F (2014) Off‐label use of hormones as an antiaging strategy: a review. Clinical Interventions in Aging 9: 1175–1186.

Schmidt M and Finley D (2013) Regulation of proteasome activity in health and disease. Biochimica et Biophysica Acta 1843: 13–25.

Sebastiani P and Perls TT (2012) The genetics of extreme longevity: lessons from the New England centenarian study. Frontiers in Genetics 3: 277.

Tan Q, Christiansen L, Thomassen M, Kruse TA and Christensen K (2013) Twins for epigenetic studies of human aging and development. Ageing Research Reviews 12: 182–187.

Vaiserman AM, Lushchak OV and Koliada AK (2016) Anti‐aging pharmacology: promises and pitfalls. Ageing Research Reviews 31: 9–35.

Van Voorhies WA, Curtsinger JW and Rose MR (2006) Do longevity mutants always show trade‐offs? Experimental Gerontology 41: 1055–1058.

Warner H (2005) Longevity genes: from primitive organisms to humans. Mechanisms of Ageing and Development 126: 235–242.

Willcox BJ, Tranah GJ, Chen R, et al. (2016) The FoxO3 gene and cause‐specific mortality. Aging Cell 15: 617–624.

Further Reading

Jazwinski SM, Belancio VP and Hill SM (2017) In: Rattan SIS (ed.) ircadian Rhythms and Their Impact on Aging. Healthy Ageing and Longevity, vol. 7. Dordrecht: Springer

Kirkwood TBL (2008) A systematic look at an old problem. Nature 451: 644–647.

Lopez‐Otin C, Blasco MA, Partridge L, Serrano M and Kroemer G (2013) The hallmarks of aging. Cell 153: 1194–1217.

McDonald RB (2014) Biology of Aging. New York: Garland Science.

Olsen A and Gill MS (2017) In: Rattan SIS (ed.) Ageing: Lessons from C. elegans. Healthy Ageing and Longevity, vol. 5. Dordrecht: Springer.

Rattan SIS and Hayflick L (2016) In: Rattan SIS (ed.) Cellular Ageing and Replicative Senescence. Healthy Ageing and Longevity, vol. 4. Dordrecht: Springer.

Rattan S and Sharma R (2017) In: Rattan SIS (ed.) Hormones in Ageing and Longevity. Healthy Ageing and Longevity, vol. 6. Dordrecht: Springer.

Vaiserman AM, Moskalev AA and Pasyukova EG (2017) In: Rattan SIS (ed.) Life Extension, Lessons from Drosophila. Healthy Ageing and Longevity, vol. 3. Dordrecht: Springer.

Vaiserman AM (2017) In: Rotella D, Martinez A and Fox D (ed.) Anti‐aging Drugs. RSC Drug Discovery Series, vol. 57. London: The Royal Society of Chemistry.

Tollefsbol TO (ed.) (2010) Epigenetics of Aging. vol. 57. Dordrecht: Springer.

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Rattan, Suresh IS(Jan 2018) Ageing Genes: Gerontogenes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0003059.pub3]