50 years in search of the «longevity» gene

Abstract

In many countries of the world mean life expectancy has lately significantly increased from 50 to 70-80 years. Twin studies have shown that genetic differences account for about 25% of the variance in adult human lifespan. However, the association with the life expectancy was proven for the only candidate gene - apolipoprotein gene, playing a great role in regulating lipoproteins metabolism. E2 allele of this gene is much more prevalent compared to E4 allele in people over 100. In animal models, single-gene mutations in genes involved in insulin/insulin-like growth factor-1 abnormal activation pathway and target of rapamycin signaling pathway have considerably extended the lifespan. The key link in regulating the insulin/insulin-like growth factor-1 abnormal activation pathway is the human forkhead box O3A transcription factor. A clear rel ationship between the lifespan and GG genotype of this gene in Japanese, German and French population was found. However, although candidate longevity genes are defined, their effects on the lifespan are still to be confirmed. Questions of gene products’ mutual influence and gene penetration are still undecided. Ethnical and geographical associations of different polymorphic alleles with aging and longevity are not completely clear. Therefore, further search and genetic and phenogenetic markers examination determining the lifespan is needed. Na+-Li+-сountertransport speed in the erythrocyte membrane, which is a genetically determined intermediate phenotype, may be one of those markers.

Keywords

lifespan / gene / population genetics / ontogenesis / polymorphism

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Chugunova D.N., Oslopov V.N.