Blocking a hunger hormone’s receptor builds stronger muscles in old age — in mice
Ghrelin is best known as the hormone that makes you hungry. Less well known is that it also appears to undermine muscle health as we age.
Sarcopenia — the gradual loss of muscle mass and strength that accompanies aging — is one of the most underappreciated health problems in an ageing population. It raises the risk of falls, slows recovery from illness, and is associated with earlier death. Effective drug treatments are scarce. Exercise helps, but not everyone can train sufficiently, and its benefits diminish at advanced ages.
Ghrelin, produced by the stomach, rises in concentration as people grow older. That might initially seem counterintuitive — a hormone that stimulates appetite should, in theory, encourage eating and therefore fuel muscles. But earlier research had already shown that deleting ghrelin in older mice restores mitochondrial function, combats obesity, and brings back muscle strength. Mitochondria are the energy generators of cells; when they malfunction, muscles struggle to produce force.
Targeting the receptor, not the hormone
The new study, published in Aging Cell, focuses not on the hormone itself but on the receptor it binds to: the ghrelin receptor, also known as GHSR (growth hormone secretagogue receptor). By suppressing this receptor in older mice, researchers achieved a measurable improvement in muscle function. This is a subtle but important distinction: blocking a receptor is pharmacologically more tractable than eliminating a hormone entirely — receptor blockers already exist for dozens of other conditions.
The researchers observed improvements in both muscle mass and functional muscle strength. The precise mechanisms are not yet fully understood, but there are indications that the ghrelin receptor influences metabolic processes in muscle tissue that become dysregulated with aging — including mitochondrial activity and protein synthesis.
From mouse to human: a long road ahead
Caution is warranted. What works in mice does not always translate to humans, and the physiology of aging differs substantially between species. Ghrelin also has multiple functions in the body, including roles in sleep regulation and cognition, meaning long-term receptor blockade could produce side effects not yet visible in short-term animal studies. Still, this research marks a potentially interesting new target in the fight against sarcopenia — a condition for which treatment options have remained disappointingly limited.