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A new study from the Max Planck Institute and University of Southern California shows that gene expression patterns linked to cellular senescence can predict biological aging, disease burden, cognitive decline, and mortality risk.
The Discovery:
Researchers analyzed blood RNA from over 3,500 older adults in the U.S. Health and Retirement Study and developed composite senescence gene expression scores. Higher scores, especially for pathways tied to DNA damage and the senescence-associated secretory phenotype (SASP), predicted faster epigenetic aging, more chronic diseases, poorer cognition, and higher 6-year mortality risk.
The Science:
The study examined five senescence-related gene sets: CSP, SIP, SRP, Senescence Summary, and SenMayo.
Scores based on the SIP (senescence-initiating pathway) and SRP (senescence-response pathway) correlated most strongly with aging outcomes.
Higher scores were linked to accelerated epigenetic clocks such as DunedinPACE, GrimAge, and PhenoAge.
Even after controlling for epigenetic age, senescence scores independently predicted mortality, multimorbidity, biological age acceleration, and cognitive decline.
Women and individuals with class II obesity had higher overall senescence activity, while those with Hispanic ethnicity tended to have lower scores.
Unlike other pathways, the CSP (cell cycle arrest) score decreased with age, possibly reflecting a protective anti-tumor function that diminishes over time.
Your Action:
Support your body’s natural defense against cellular senescence by maintaining healthy weight, quality sleep, and regular exercise. These behaviors reduce DNA damage and inflammation that trigger senescence. Emerging senolytic and gene-targeted therapies may soon complement these lifestyle measures, but prevention still begins with daily habits.
Bottom Line:
Measuring senescence gene activity in blood may offer a new biomarker for predicting aging rate and long-term health.
Source:
Gene expression composite scores of cellular senescence predict aging health outcomes in the Health and Retirement Study, Nature Communications, Wu Q. et al., Max Planck Institute for Human Development and University of Southern California.
https://doi.org/10.1038/s41467-025-64835-8
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