Format

Send to

Choose Destination
Elife. 2016 Nov 22;5. pii: e19130. doi: 10.7554/eLife.19130.

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

Author information

1
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States.
2
Department of Pathology, University of Michigan Medical School, Ann Arbor, United States.
3
Geriatrics Center, University of Michigan Medical School, Ann Arbor, United States.
4
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, United States.
5
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States.
6
Department of Genetics, Albert Einstein College of Medicine, Bronx, United States.
7
Department of Biology, University of Rochester, Rochester, United States.
8
Broad Institute, Cambridge, 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.

KEYWORDS:

aging; cell biology; evolutionary biology; gene expression; genomics; human; lifespan; metabolite profiling; mouse; rat; rhesus macaque

PMID:
27874830
PMCID:
PMC5148604
DOI:
10.7554/eLife.19130
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center