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

Siming Ma, Akhil Upneja, Andrzej Galecki, Yi Miau Tsai, Charles F. Burant, Sasha Raskind, Quanwei Zhang, Zhengdong D. Zhang, Andrei Seluanov, Vera Gorbunova, Clary B. Clish, Richard A. Miller, Vadim N. Gladyshev

Research output: Contribution to journalArticle

25 Scopus citations

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.

Original languageEnglish (US)
Article numbere19130
JournaleLife
Volume5
Issue numberNOVEMBER2016
DOIs
StatePublished - Nov 22 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Ma, S., Upneja, A., Galecki, A., Tsai, Y. M., Burant, C. F., Raskind, S., Zhang, Q., Zhang, Z. D., Seluanov, A., Gorbunova, V., Clish, C. B., Miller, R. A., & Gladyshev, V. N. (2016). Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity. eLife, 5(NOVEMBER2016), [e19130]. https://doi.org/10.7554/eLife.19130