Abstract
Senescent cells accumulate in most tissues with organismal aging, exposure to stressors, or disease progression. It is challenging to identify senescent cells because cellular senescence signatures and phenotypes vary widely across distinct cell types and tissues. Here we developed an analytical algorithm that defines cell-type-specific and universal signatures of cellular senescence across a wide range of cell types and tissues. We utilize 72 mouse and 64 human weighted single-cell transcriptomic signatures of cellular senescence to create the SenePy scoring platform. SenePy signatures better recapitulate in vivo cellular senescence than signatures derived from in vitro senescence studies. We use SenePy to map the kinetics of senescent cell accumulation in healthy aging as well as multiple disease contexts, including tumorigenesis, inflammation, and myocardial infarction. SenePy characterizes cell-type-specific in vivo cellular senescence and could lead to the identification of genes that serve as mediators of cellular senescence and disease progression.
© 2025. The Author(s).
MeSH terms
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Aging / genetics
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Algorithms
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Animals
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Cellular Senescence* / genetics
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Gene Expression Profiling* / methods
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Humans
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Inflammation / genetics
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Male
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Mice
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Mice, Inbred C57BL
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Myocardial Infarction / genetics
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Myocardial Infarction / pathology
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Single-Cell Analysis* / methods
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Transcriptome* / genetics
Grants and funding
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R01-AG091545/U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
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P01HL160469/U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
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R01-HL152515/U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
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R01 HL152515/HL/NHLBI NIH HHS/United States
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R01-HL163978/U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
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P01 HL160469/HL/NHLBI NIH HHS/United States
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F31-AG090005/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
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T32- HL139439/U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
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F31 AG090005/AG/NIA NIH HHS/United States
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R01 HL163978/HL/NHLBI NIH HHS/United States
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T32 HL139439/HL/NHLBI NIH HHS/United States
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R01 AG091545/AG/NIA NIH HHS/United States