Cellular senescence is increasingly recognized as a hallmark of aging and a significant contributor to various age-related morbidities. The phenomenon of senescence is characterized by a pro-inflammatory secretome known as the senescence-associated secretory phenotype (SASP), which can be tracked in circulation. This tracking raises the intriguing possibility that the senescence burden, along with the susceptibility to age-related morbidity, can be assessed noninvasively in clinical settings.
This review consolidates evidence focused on human biomarkers of senescence found in circulation. It highlights emerging drug and lifestyle-based senotherapeutic interventions that may modulate senescence burden and associated clinical parameters. The clinical parameters linked to the circulating senescence burden generally fall into four interrelated health domains:
- Neurodegeneration
- Pulmonary disease
- Cardiometabolic disease
- Musculoskeletal disorders
For each of these domains, the review explores the biological basis for the negative impacts of senescence, supported by both clinical and preclinical models. The accumulation of senescent cells appears to suppress stemness throughout the body, suggesting a causal role in age-related decline. This highlights potential novel therapeutic avenues that could be explored to mitigate the effects of senescence.
Importantly, certain circulating biomarkers of senescence, such as GDF15 and Activin A, have demonstrated clinical relevance across multiple studies and are implicated in various morbidities across the aforementioned health domains. These insights provide a framework for understanding the role of senescence in aging and the 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 or studies demonstrating the efficacy of specific interventions based on the identified biomarkers.
Evidence scorecard
- Evidence class: review
- Human status: unclassified
- Publication types: Journal Article, Review