Cellular senescence is recognized as a hallmark of aging, contributing significantly to various age-related morbidities and declines in health. A defining feature of senescent cells is their pro-inflammatory secretome, termed the senescence-associated secretory phenotype (SASP). This review consolidates evidence focused on human studies that identify circulating biomarkers of senescence and discusses emerging therapeutic interventions aimed at modulating senescence burden.
The review highlights that when SASP factors are tracked in circulation, they correlate with age-related clinical traits and diseases. This raises the intriguing possibility that the senescence burden, along with the susceptibility to age-related morbidity, could be assessed noninvasively in clinical settings.
Clinical parameters associated with the circulating senescence burden are categorized into four interrelated health domains: neurodegeneration, pulmonary disease, cardiometabolic disease, and musculoskeletal disorders. For each of these domains, the authors explore the biological mechanisms underlying the negative impacts of senescence, supported by both clinical and preclinical models.
One significant finding is that the accumulation of senescent cells often suppresses stemness throughout the body, suggesting a causal role for senescence in age-related decline. This insight underscores the potential for novel therapeutic avenues to address these issues.
Notably, some circulating biomarkers of senescence, such as GDF15 and Activin A, show cross-study clinical relevance and are implicated in morbidities across multiple health domains. The review emphasizes the importance of these biomarkers in understanding the role of senescence in aging and the development of diagnostic biomarker panels that could enhance clinical care in the future.
What this study does not show
This review does not provide direct evidence from clinical trials demonstrating the efficacy of specific interventions targeting senescence biomarkers.
Evidence scorecard
- Analytic validity: established
- Clinical validity: partial
- Clinical utility: not established
The evidence is based on a review of existing literature focused on human studies.