Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity.

Abstract:

: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.

journal_name

Elife

journal_title

eLife

authors

Ma S,Upneja A,Galecki A,Tsai YM,Burant CF,Raskind S,Zhang Q,Zhang ZD,Seluanov A,Gorbunova V,Clish CB,Miller RA,Gladyshev VN

doi

10.7554/eLife.19130

subject

Has Abstract

pub_date

2016-11-22 00:00:00

issn

2050-084X

journal_volume

5

pub_type

杂志文章

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