Genomic approaches for discovery of lifespan interventions

2018-05-22T18:06:06Z (GMT) by V.N. Gladyshev
Age is a major risk factor for human chronic diseases. The aging process can be regulated during evolution (e.g. mammals show >100-fold difference in lifespan) development (e.g. cells within individual cell types show widely different turnover rates) and in response to interventions (e.g. calorie restriction, rapamycin, growth hormone deficiency). We employ this diversity to shed light on mechanisms that regulate lifespan. For this, we apply comparative genomics to short- and long-lived species and carry out analyses across panels of mammals. First, we sequenced the genomes of several mammals with exceptional lifespan and identified genes that may contribute to their longevity. Second, we carried out analyses of gene expression, metabolites and elements across large panels of mammals. Third, we analyzed gene expression across different cell types that are characterized by different longevity (cell turnover). Fourth, we analyzed mouse models of longevity. These studies point to both unique (to cells, lineages, interventions) and common adaptations to longevity involving various pathways. In turn, the resulting gene expression patterns suggest concrete strategies for longevity interventions. I may also discuss how aging can be better understood by following molecular damage in the form of low molecular weight species and somatic mutations derived from the analysis of cancer genomes. A better understanding of mechanisms of aging and lifespan control should lead to targeting the aging process itself, thereby extending lifespan.




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