Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity
- Brigham and Women's Hospital, Harvard Medical School, United States
- University of Michigan Medical School, United States
- Albert Einstein College of Medicine, United States
- University of Rochester, United States
- Broad Institute, United States
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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Funding
NIH Office of the Director (AG047745)
- Vadim N Gladyshev
National Institutes of Health (AG047200)
- Zhengdong D Zhang
- Andrei Seluanov
- Vera Gorbunova
- Vadim N Gladyshev
National Institutes of Health (AG023122)
- Vadim N Gladyshev
National Institutes of Health (DK089503)
- Vadim N Gladyshev
National Institutes of Health (DK097153)
- Vadim N Gladyshev
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Ma et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity
eLife 5:e19130.
https://doi.org/10.7554/eLife.19130
