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Cited by 162Genetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and SenescenceSirtuins and Resveratrol in Medicine

Distinct longevity mechanisms across and within species and their association with aging

Open access
Tyshkovskiy, Alexander, Ma, Siming, Shindyapina, Anastasia V., Tikhonov, Stanislav, Lee, Sang-Goo, Bozaykut, Perinur, Castro, José P., Seluanov, Andrei +5 more·2023·Cell
DOI 10.1016/j.cell.2023.05.002PMC PMC11192172
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Abstract

Lifespan varies within and across species, but the general principles of its control remain unclear. Here, we conducted multi-tissue RNA-seq analyses across 41 mammalian species, identifying longevity signatures and examining their relationship with transcriptomic biomarkers of aging and established lifespan-extending interventions. An integrative analysis uncovered shared longevity mechanisms within and across species, including downregulated Igf1 and upregulated mitochondrial translation genes, and unique features, such as distinct regulation of the innate immune response and cellular respiration. Signatures of long-lived species were positively correlated with age-related changes and enriched for evolutionarily ancient essential genes, involved in proteolysis and PI3K-Akt signaling. Conversely, lifespan-extending interventions counteracted aging patterns and affected younger, mutable genes enriched for energy metabolism. The identified biomarkers revealed longevity interventions, including KU0063794, which extended mouse lifespan and healthspan. Overall, this study uncovers universal and distinct strategies of lifespan regulation within and across species and provides tools for discovering longevity interventions.

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Crossref · 10.1016/j.cell.2023.05.002

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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 [36]

  • Activation of the TSP that generates cysteine and culminates in production of GSH and taurine has previously been associated with pro-longevity interventions.

    “Activation of the TSP that generates cysteine and culminates in production of GSH and taurine has previously been associated with pro-longevity interventions.36,70”

    From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [36]

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References 178 · Cited by 162

Authors
Tyshkovskiy, A., Ma, S., Shindyapina, A. V., Tikhonov, S., Lee, S.-G., Bozaykut, P., Castro, J. P., Seluanov, A., Schork, N. J., Gorbunova, V., Dmitriev, S. E., Miller, R. A., & Gladyshev, V. N.
Affiliations
  • Brigham and Women's Hospital (US)
  • Lomonosov Moscow State University (RU)
  • University of Rochester (US)
  • Translational Genomics Research Institute (US)
  • University of Michigan (US)
  • Broad Institute (US)
Corresponding author
Gladyshev, Vadim N.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2023-06
Volume
186
Issue
13
Pages
2929-2949.e20
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2023.05.002
PMC
PMC11192172
OpenAlex
W4379208082
Cited by
162
References
178
Citations by year
2026: 45 · 2025: 64 · 2024: 36 · 2023: 17
FWCI
10.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (UH3AG064706, UH2AG064706, P01AG047200, R37AG046320)
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
longevity, lifespan regulation, aging, cross-species comparison, mammals, insulin-like growth factor I, mitochondrial translation, innate immune response, cellular respiration, proteolysis, PI3K/Akt signaling, energy metabolism, healthspan
MeSH terms
Aging, Animals, Longevity, Mammals, Phosphatidylinositol 3-Kinases, Gene Expression Profiling, Mice

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