Modalities of gene action predicted by the classical evolutionary biological theory of aging.
What might now be referred to as the "classical" evolutionary biological theory of why we age has had a number of serious challenges in recent years. While the theory might therefore have to be modified under certain circumstances, in the author's opinion, it still provides the soundest theoretical basis for thinking about how we age. Nine modalities of gene action that have the potential to modulate processes of aging are reviewed, including the two most widely reviewed and accepted concepts ("antagonistic pleiotropy" and "mutation accumulation"). While several of these nine mechanisms can be regarded as derivatives of the antagonistic pleiotropic concept, they frame more specific questions for future research. Such research should pursue what appears to be the dominant factor in the determination of intraspecific variations in longevity-stochastic mechanisms, most likely based upon epigenetics. This contrasts with the dominant factor in the determination of interspecific variations in longevity-the constitutional genome, most likely based upon variations in regulatory loci.
Martin
George M
GM
Departments of Pathology and Genome Sciences, P.O. Box 357470, University of Washington, Seattle, WA 98195-7470, USA. gmmartin@u.washington.edu
D000375:Aging / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008136:Longevity; D008954:Models, Biological; D009154:Mutation; D013269:Stochastic Processes