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

2016/11/22 by Siming Ma, Akhil Upneja, Andrzej T. Gałecki +10 · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Genetics, Aging, and Longevity in Model Organisms #Adipose Tissue and Metabolism #Metabolomics and Mass Spectrometry Studies

paper · doi:10.7554/elife.19130

openalex publication_date 2016/11/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

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.

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