Senescent cells accumulate in tissues with age to promote degenerative aging. Senescent cells cause harm via the signals that they send to other cells, the senescence-associated secretory phenotype (SASP). The SASP is by no means fully understood, and while it clearly contains many pro-inflammatory and pro-growth signals, it probably has many other effects as well. Here, researchers provide evidence for one specific SASP signal molecule to interfere in the benefits of exercise. Clearance of senescent cells should therefore produce an enhanced response to exercise in old individuals, in addition to the other benefits already demonstrated in a sizeable number of animal studies.
Adaptation to physiological stress is fundamental to health but varies widely among individuals. In humans, this heterogeneity is evident in markedly different gains in fitness in response to identical exercise training. The molecular determinants of this variable "trainability" remain poorly understood. Here we identify insulin-like growth factor binding protein-7 (IGFBP7), a senescence-associated secreted protein, as a circulating constraint on exercise adaptation.
Plasma proteomics in older adults enrolled in a randomized exercise trial revealed that IGFBP7 levels inversely predicted fitness gains after one year of high-intensity interval training despite similar baseline fitness. In mice, genetic deletion of IGFBP7 markedly amplified training-induced gains in exercise capacity across distinct training protocols, whereas somatic overexpression abolished this advantage. In the UK Biobank, lower IGFBP7 levels were associated with reduced mortality and multiple incident age-related diseases, mirroring the breadth of ties between fitness and healthspan.
Together, these findings identify circulating IGFBP7 as a molecular brake on physiological plasticity in response to exercise, linking training responsiveness, aging biology, and health outcomes.
Link: https://doi.org/10.64898/2026.02.09.26345899
View the full article at FightAging
