Growth hormone receptor suppression in midlife modestly extends lifespan in mice

Researchers have shown that ablation of the growth hormone receptor initiated at midlife—specifically at 12 months of age in mice—produces significant lifespan extension in both sexes, though modest compared to lifelong suppression: less than 10% in males and less favorable outcomes in females. The mechanism operates through hepatic transcriptomic remodeling at single-cell resolution, including B-cell reduction and a shift toward feminized gene expression patterns in male hepatocytes, consistent with impaired pulsatile GH-STAT5 signaling. Beyond these molecular effects, male mice demonstrated improved insulin sensitivity and protection against age-related neuromuscular deterioration and bone microarchitecture decline, despite increased adiposity. However, the existence of Laron syndrome in humans—the analogous condition caused by growth hormone receptor loss-of-function mutations—which does not produce meaningful lifespan extension in patients, suggests skepticism about clinical translation of this mechanism into human anti-aging therapies.