Gene expression composite scores of cellular senescence predict aging health outcomes in the Health and Retirement Study

Qiao Wu (), Eric T. Klopack, Jung Ki Kim, T. Em Arpawong, Bharat Thyagarajan, Steve Cole, Jessica D. Faul, Fengxue Zhou and Eileen M. Crimmins ()
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Qiao Wu: Max Planck Research Group Biosocial–Biology, Social Disparities, and Development
Eric T. Klopack: University of Southern California
Jung Ki Kim: University of Southern California
T. Em Arpawong: University of Southern California
Bharat Thyagarajan: University of Minnesota
Steve Cole: University of California Los Angeles (UCLA)
Jessica D. Faul: University of Michigan
Fengxue Zhou: Charité—Universitätsmedizin Berlin
Eileen M. Crimmins: University of Southern California

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Cellular senescence, a hallmark of aging, can be quantified by the gene expression composite scores for the canonical senescence pathway (CSP), senescence initiating pathway (SIP), senescence response pathway (SRP), a summary of the three, and the SenMayo gene list; however, these have not been probed in representative populations. Using RNA sequencing data from the U.S. representative Health and Retirement Study (HRS) sample (N = 3580), we examine how these composite scores relate to sociobehavioral factors and aging-related outcomes. Senescence scores generally increase with age except for CSP. Higher scores are observed in women and individuals with class II obesity. All scores, except for CSP, are associated with accelerated epigenetic aging, physiological dysregulation, multimorbidity, cognitive decline, and 6-year mortality (all p

Date: 2025
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DOI: 10.1038/s41467-025-64835-8

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