Cited by 167Genetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and SenescenceSirtuins and Resveratrol in Medicine

Identification and Application of Gene Expression Signatures Associated with Lifespan Extension

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Tyshkovskiy, Alexander, Bozaykut, Perinur, Borodinova, Anastasia A., Gerashchenko, Maxim V., Ables, Gene P., Garratt, Michael, Khaitovich, Philipp, Clish, Clary B. +2 more·2019·Cell Metabolism

Abstract

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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Crossref · 10.1016/j.cmet.2019.06.018

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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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2 of the 150 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Baze MM, Schlauch K, and Hayes JP (2010a). Gene expression of the liver in response to chronic hypoxia. 275– 288. PMC2869108 20103700
  2. Coschigano KT, Clemmons D, Bellush LL, and Kopchick JJ (2000). Assessment of growth parameters and lifespan of GHR/BP gene-disrupted mice. Endocrinology 141, 2608– 2613. 10875265
  3. Kabil O, Vitvitsky V, Xie P, and Banerjee R (2011). The quantitative significance of the transsulfuration enzymes for H2S production in murine tissues. Antioxid. Redox Signal 15, 363– 372. 21254839 PMC3118817

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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.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2019-09
Volume
30
Issue
3
Pages
573-593.e8
ISSN
1550-4131 (ISSN-L)
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
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

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