Cellular senescence is increasingly recognized as a hallmark of aging, contributing significantly to various age-related morbidities and declines in health. A notable feature of senescent cells is their pro-inflammatory secretome, known as the senescence-associated secretory phenotype (SASP). This review consolidates existing human-focused evidence on circulating biomarkers of senescence and explores their mechanistic impacts across multiple health domains.
When tracked in circulation, SASP factors have been found to 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, can be assessed noninvasively in clinical settings. The review identifies several key biomarkers associated with senescence that could potentially serve as diagnostic tools.
Health Domains Impacted by Senescence
The clinical parameters linked with circulating senescence biomarkers generally fall into four interrelated health domains:
- Neurodegeneration: Senescence is implicated in cognitive decline and neurodegenerative diseases.
- Pulmonary Disease: The accumulation of senescent cells may contribute to respiratory conditions.
- Cardiometabolic Disease: Senescence is associated with cardiovascular health and metabolic disorders.
- Musculoskeletal Disorders: Aging-related decline in musculoskeletal health is linked to senescence.
For each of these domains, the review discusses the biological mechanisms through which senescence negatively impacts health, drawing on both clinical and preclinical models. The findings suggest that the accumulation of senescent cells may suppress stemness throughout the body, indicating a causal role in age-related decline.
Importantly, certain circulating biomarkers of senescence, such as GDF15 and Activin A, have shown cross-study clinical relevance and are implicated in morbidities across multiple health domains. This highlights their potential as targets for therapeutic interventions.
What this study does not show
This review does not provide direct evidence of specific therapeutic outcomes resulting from the modulation of senescence biomarkers.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is based on a review of existing literature on biomarkers of senescence in humans.