Year: 2026
Type: preprint
Abstract: 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.
Source: medRxiv
Authors: Nicholas Houstis, Qiulian Zhou, Yuling Chen, Sonja Mittag, Vinita Chowdhury, Chao Wu, Meixi Quan, Azrul Kadir, Giulia Guerra, Sashi Weerawarana, Danielle Szczesniak, Justin Guerra, James Rhee, J. Sawalla Guseh, Haobo Li, Bo Li, Aurel B. Leuchtmann, Jorge Ruas, Ulrik Wisloff, Dorthe Stensvold, Anthony Rosenzweig
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7128688053