Growth hormone receptor antagonism extends median and maximal lifespan in mice by 7–9%, with females showing greater longevity gains than males. This finding establishes proof of concept for GH antagonists as potential anti-aging interventions, with the FDA-approved drug Pegvisomant representing an existing therapeutic candidate.
Key Points
- GH antagonism extended maximal lifespan by 186–265 days in mice.
- Female mice showed greater lifespan extension than males (265 vs 186 days).
- GHA mice exhibited reduced frailty and improved grip strength at advanced age.
Longevity Analysis
Growth hormone action has long been implicated in aging across multiple species. By demonstrating that antagonizing GH signaling improves both lifespan and physical resilience—measured through grip strength and frailty markers—this work suggests that hormonal regulation, particularly the reduction of anabolic signaling in advanced age, may support longevity through mechanisms independent of caloric restriction or other canonical interventions. The sex-dependent response (stronger in females) indicates that hormonal context shapes the magnitude of lifespan extension, a pattern relevant to understanding why aging trajectories diverge by sex. The persistence of strength despite increased adiposity raises questions about body composition remodeling under GH antagonism and whether the mechanism operates through altered energy allocation or changes in cellular regeneration patterns.
Original published by Wiley Aging Cell, by Edward O. List, Darlene E. Berryman, Grace S. Lach, Delaney F. Minto, Keeley Weese, John J. Kopchick .