Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity
Open accessAbstract
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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Oxidative damage to cell proteins, lipids and most importantly nuclear DNA is a critical element of the aging process.
“The oxidative damage to cell proteins, lipids and most importantly nuclear DNA is now believed to be a critical element of the aging process [94,95,96,97,98,99,100].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [96]
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References 106 · Cited by 89
- Authors
- 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.
- Affiliations
- Brigham and Women's Hospital (US)
- Department of Pathology, University of Michigan Medical School, Ann Arbor, United States
- University of Michigan (US)
- Albert Einstein College of Medicine (US)
- National Institutes of Health (US)
- University of Rochester (US)
- Broad Institute (US)
- Corresponding author
- Gladyshev, Vadim N
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-11-22
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5148604
- OpenAlex
- W2552812120
- Cited by
- 89
- References
- 106
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 14 · 2022: 4 · 2021: 16 · 2020: 11 · 2019: 7 · 2018: 8 · 2017: 8
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (DK097153, AG047200, AG047745, AG023122, DK089503)
- Life Extension Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- species longevity, DNA repair, glucose metabolism, dermal fibroblasts, metabolite profiling, gene expression profiling, amino acids, lysophosphatidylcholine, lysophosphatidylethanolamine, proteolysis, protein trafficking, cross-species comparison
- MeSH terms
- Animals, Birds, Cells, Cultured, DNA Repair, Energy Metabolism, Fibroblasts, Longevity, Mammals, Cell Culture Techniques, Gene Expression Profiling, Metabolomics
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