Ageing Genes: Gerontogenes

Abstract

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.
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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.

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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. http://www.els.net [doi: 10.1002/9780470015902.a0003059.pub3]