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Disruption of GH Receptor Increases Lifespan in Female Mice

Disrupting the growth hormone receptor (Ghr) gene in adult mice increased the maximal lifespan in the female mice, but not the males, according to a study recently published in Endocrinology.

Researchers led by John J. Kopchick, PhD, of the Edison Biotechnology Institute and Ohio University in Athens, write that many animals have shown increased lifespans when GH/insulin/IGF-1 actions are reduced. Yet, GH and IGF-1 have unique and overlapping actions.  Kopchick and his team note that they have previously disrupted the Ghr gene globally and found that those mice (labeled GHRKO for “GHR gene knockout”) had increased lifespans. “In fact, one GHRKO mouse lived for almost 5 years and currently holds the record for the longest-lived laboratory mouse,” the authors write.

For the current study, the researchers wanted to determine whether temporally controlled Ghr gene deletion in adult mice would affect metabolism and longevity. Therefore, they analyzed male and female mice separated into two cohorts.  To induce conditional Ghr gene disruption, 6-week-old mice received 100-uL ip injections of 10-mg/mL tamoxifen dissolved in peanut oil once per day over 5 consecutive days for a total of 5 mg of tamoxifen. Control mice received injections of just peanut oil.

The researchers found that when adult mice have their Ghr gene disrupted, they showed improved insulin sensitivity but only females showed improved longevity.  The authors note that this sex-specific result should be studied more. They also write that there are some limitations to this study, namely that the Ghr gene was not disrupted in similar fashion in all tissues. Finally, the authors note that “if further studies confirm that blocking GH action in adulthood provides successful health outcomes, then GHR-targeted therapeutics should be considered for improving health and longevity in humans.”