Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevityстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 11 апреля 2019 г.
Аннотация:Mammalian lifespan differs by >100 fold, but the mechanisms associated with such
longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts
isolated from 16 species of mammals and maintained under identical cell culture conditions. We
developed a pipeline for obtaining species-specific ortholog sequences, profiled gene expression
by RNA-seq and small molecules by metabolite profiling, and identified genes and metabolites
correlating with species longevity. Cells from longer lived species up-regulated genes involved in
DNA repair and glucose metabolism, down-regulated proteolysis and protein transport, and
showed high levels of amino acids but low levels of lysophosphatidylcholine and
lysophosphatidylethanolamine. The amino acid patterns were recapitulated by further analyses of
primate and bird fibroblasts. The study suggests that fibroblast profiling captures differences in
longevity across mammals at the level of global gene expression and metabolite levels and reveals
pathways that define these differences.