Identification and Application of Gene Expression Signatures Associated with Lifespan Extension
Open accessAbstract
Several pharmacological, dietary, and genetic interventions that increase mammalian lifespan are known, but general principles of lifespan extension remain unclear. Here, we performed RNA sequencing (RNA-seq) analyses of mice subjected to 8 longevity interventions. We discovered a feminizing effect associated with growth hormone regulation and diminution of sex-related differences. Expanding this analysis to 17 interventions with public data, we observed that many interventions induced similar gene expression changes. We identified hepatic gene signatures associated with lifespan extension across interventions, including upregulation of oxidative phosphorylation and drug metabolism, and showed that perturbed pathways may be shared across tissues. We further applied the discovered longevity signatures to identify new lifespan-extending candidates, such as chronic hypoxia, KU-0063794, and ascorbyl-palmitate. Finally, we developed GENtervention, an app that visualizes associations between gene expression changes and longevity. Overall, this study describes general and specific transcriptomic programs of lifespan extension in mice and provides tools to discover new interventions.
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Multiple longevity interventions in rodents are associated with rewiring of the transsulfuration pathway that feeds into taurine synthesis.
“Multiple longevity interventions in rodents have been associated with the rewiring of the TSP that feeds into taurine synthesis.34–38”
From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [34]
In Results and Discussion, under “Common gene signatures of longevity interventions” (page unavailable), the paper reports increased hepatic expression of Cth after most lifespan-extending interventions in mice. That supports a change in one sulfur-metabolism gene, but the passage links Cth to glutathione and H2S production; it does not establish rewiring of the transsulfuration pathway feeding into taurine synthesis. (LLM, conf=0.84)
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- Authors
- Tyshkovskiy, A., Bozaykut, P., Borodinova, A. A., Gerashchenko, M. V., Ables, G. P., Garratt, M., Khaitovich, P., Clish, C. B., Miller, R. A., & Gladyshev, V. N.
- Affiliations
- Skolkovo Institute of Science and Technology (RU)
- Brigham and Women's Hospital (US)
- Russian Academy of Sciences (RU)
- Orentreich Foundation for the Advancement of Science (US)
- University of Michigan (US)
- Broad Institute (US)
- Corresponding author
- Gladyshev, Vadim N.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 30
- Issue
- 3
- Pages
- 573-593.e8
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6907080
- OpenAlex
- W2963842764
- Cited by
- 167
- References
- 150
- Citations by year
- 2026: 22 · 2025: 24 · 2024: 22 · 2023: 30 · 2022: 19 · 2021: 31 · 2020: 15 · 2019: 4
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- lifespan extension, longevity interventions, gene expression signatures, growth hormone, sex differences, hepatic gene expression, oxidative phosphorylation, drug metabolism, chronic hypoxia, ascorbyl palmitate
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Aging, Animals, Hypoxia, Ascorbic Acid, Female, Gene Expression Regulation, Life Expectancy, Liver, Longevity, Male, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Morpholines, Pyrimidines, Sirolimus, Caloric Restriction, Mice, Gene Knockout Techniques, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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