Ablating growth hormone receptor signaling at midlife extends lifespan in both sexes while preserving metabolic health and physical function. Single-cell liver analysis reveals sex-specific transcriptional remodeling that correlates with these longevity benefits, suggesting the GH/IGF-1 axis remains therapeutically modifiable well into adulthood.
Key Points
- Midlife GH receptor disruption extends lifespan without impairing somatic growth
- Males show improved insulin sensitivity and preserved bone and neuromuscular function
- Liver transcriptional remodeling includes sex-dimorphic patterns and B-cell reduction
Longevity Analysis
This work establishes that suppressing growth hormone signaling during middle age—rather than requiring lifelong genetic ablation—can produce lifespan extension and metabolic resilience. The finding that hepatic gene expression undergoes substantial remodeling, particularly a feminization of the male transcriptome under GH resistance, points to coordinated changes across energy production and hormonal regulation that permit sustained health into advanced age. The preservation of neuromuscular and skeletal integrity despite increased adiposity indicates the body can maintain structural and functional capacity even when hormonal signaling patterns shift significantly. This suggests interventions targeting this pathway in midlife humans might extend healthspan without the developmental or reproductive costs associated with lifetime GH suppression.
Original published by Wiley Aging Cell, by Silvana Duran‐Ortiz, Edward O. List, Jonathan A. Young, Yuji Ikeno, Shouan Zhu, Todd McHugh, Patrick M. O'Connor, Minhoo Kim, Bérénice A. Benayoun, Fabian Benencia, Reetobrata Basu, Emmanuel A. Gotte, Darlene E. Berryman, John J. Kopchick .