Cellular senescence is recognized as a hallmark of aging, contributing significantly to various age-related morbidities and declines. A notable feature of senescent cells is their pro-inflammatory secretome, referred to as the senescence-associated secretory phenotype (SASP). This review consolidates evidence focused on human biomarkers of senescence found in circulation, highlighting their association with clinical traits and diseases related to aging.
When SASP factors are tracked in circulation, they show a correlation with age-related clinical traits and diseases. This raises the intriguing possibility that the burden of senescence, along with the susceptibility to age-related morbidities, can be assessed noninvasively in clinical settings. The review discusses how these biomarkers can serve as indicators of senescence burden across various health domains.
Health Domains Affected by Senescence
The clinical parameters associated with circulating senescence burden typically fall into four interrelated health domains:
- Neurodegeneration
- Pulmonary Disease
- Cardiometabolic Disease
- Musculoskeletal Disorders
For each of these domains, the review explores the biological mechanisms that underlie the negative impacts of senescence, drawing from both clinical and preclinical models. The accumulation of senescent cells is suggested to suppress stemness throughout the body, indicating a causal role of senescence in age-related decline.
Among the biomarkers discussed, GDF15 and Activin A are highlighted for their cross-study clinical relevance, as they are implicated in morbidities across multiple health domains. These insights provide a framework for understanding the role of senescence in aging and the potential development of diagnostic biomarker panels that could enhance future clinical care.
What this study does not show
This review does not provide direct evidence from clinical trials demonstrating the effectiveness of specific therapeutic interventions based on the identified biomarkers.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is based on a review of existing literature and does not include new clinical trial data.