Growth hormone receptor deletion at 12 months extended lifespan in female mice

Growth hormone receptor deletion at 12 months extended lifespan in female mice

In a paper published on September 5, researchers deleted the Ghr gene, which encodes the growth hormone receptor, in mice. In females, median lifespan increased from 929 to 1003 days, while the longest recorded lifespan increased from 1097 to 1231 days. In males, the survival curves differed statistically, while changes in metabolism and physical performance were also observed mainly in males.

Reducing growth hormone signaling early in life had previously extended lifespan in mice, but it had also altered development throughout the body. The same research group had already deleted Ghr at six months. In the new experiment, the intervention was delayed until 12 months, after most growth and reproductive maturation had occurred. This design allowed the authors to test whether this pathway still affects aging when altered in middle age.

The mice received tamoxifen for five days. Tamoxifen activated an enzyme that cut the DNA within the Ghr gene and removed that segment. Control animals received peanut oil without tamoxifen. In the treated mice, blood levels of IGF-1, a protein produced by the liver in response to growth hormone, decreased, while growth hormone levels increased. The combination of low IGF-1 and high growth hormone indicates that the tissues had become less responsive to growth hormone signaling.

Mice of both sexes were followed until natural death. In females, median lifespan increased by 8%, and the longest recorded lifespan increased by 12%. Males became more responsive to insulin. After adjustment for lean body mass, they remained longer on a rotating rod and exerted greater force on a grip strength meter. The structure of trabecular bone in their vertebrae was also better preserved.

Because the liver produces most of the IGF-1 found in blood, the researchers examined gene activity in individual liver cell nuclei. In males, hepatocytes, the main cells of the liver, showed larger changes in gene expression programs. Some genes associated with the male response to growth hormone became less active, while some genes characteristic of the female response became more active. The experiment therefore showed that males and females followed different response patterns in both survival and liver function.