A comprehensive NIH-authored compendium identifies circulating senescence-associated secretory phenotype (SASP) factors — particularly GDF15 and Activin A — as cross-domain biomarkers linking cellular senescence burden to four major age-related disease categories: neurodegeneration, pulmonary disease, cardiometabolic disease, and musculoskeletal disorders. A unifying mechanistic thread emerges: senescence accumulation suppresses tissue stemness systemwide, suggesting a causal rather than merely correlative role in functional decline.
The significance here extends beyond cataloguing. The field of geroscience has long needed translatable, noninvasive biomarkers that can quantify biological aging in living patients — not post-mortem tissue. If validated prospectively, a circulating SASP panel anchored by GDF15 and Activin A could function analogously to lipid panels for cardiovascular risk: routine, actionable, and predictive before disease manifests. GDF15 already has traction in sarcopenia and cancer cachexia research, while Activin A's roles in inflammation and muscle wasting position both as genuinely compelling candidates.
Critically, this is a review, not primary data — its value is synthesis, not discovery. The authors acknowledge that causality between circulating SASP levels and clinical outcomes remains incompletely established in humans; most mechanistic evidence still derives from preclinical models. The emerging senotherapeutic landscape (senolytics, senomorphics, lifestyle interventions) adds clinical urgency, but trial evidence modulating these specific biomarkers remains sparse. Incremental but architecturally important — this compendium provides the diagnostic framework geroscience needs to operationalize senescence measurement in clinical practice.
