Both median and maximal lifespan were significantly increased in male and female GHA transgenic mice, demonstrating for the first time that GH antagonism can improve health and extend lifespan.
Median lifespan was significantly extended in both male and female GHA transgenic mice.
Maximal lifespan was significantly extended in both male and female GHA transgenic mice.
GHA transgenic mice at 2 years of age were less frail and had enhanced grip strength compared to controls.
GHA transgenic mice displayed increased adiposity alongside improved health and longevity measures.
A prior study with methodological limitations had failed to detect lifespan extension in GHA mice, and the current study was designed to address those limitations.
The GH receptor antagonist mechanism underlying GHA transgenic mice was based on mutation of a conserved glycine residue in the GH molecule.
This research suggests that blocking the action of growth hormone (GH) in mice can significantly extend both how long they typically live (median lifespan) and the maximum age they can reach. Scientists used a special strain of transgenic mice that produce a modified version of GH which blocks the normal GH receptor rather than activating it — essentially acting as a molecular 'off switch' for GH signaling. Both male and female mice with this modification lived significantly longer, with females gaining up to 265 extra days of maximum lifespan and males gaining up to 186 extra days. Importantly, these longer-lived mice were also healthier at old age: at two years old, they showed less frailty and stronger grip strength compared to normal mice. Interestingly, the GHA mice were heavier and had more body fat than normal mice, yet they were still healthier and longer-lived. This challenges the common assumption that higher body fat is always linked to worse health outcomes, at least in the specific context of reduced GH signaling. A previous study had failed to find lifespan benefits in this same mouse line, but the current study corrected methodological problems from that earlier work and successfully detected the effect. This research matters because it provides the first direct evidence that antagonizing — rather than simply eliminating — GH signaling can extend lifespan in an animal model. This is relevant to human medicine because a drug that works by the same mechanism, Pegvisomant (Somavert), is already FDA-approved for treating a condition called acromegaly (caused by excess GH). This research suggests that drugs in this class could potentially have broader applications in promoting healthy aging, though this remains to be tested in humans.
List E, Berryman D, Lach G, Minto D, Weese K, Kopchick J. (2026). Growth Hormone Receptor Antagonism Extends Lifespan.. Aging cell. https://doi.org/10.1111/acel.70697