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Publication : Growth hormone receptor gene disruption in mature-adult mice improves male insulin sensitivity and extends female lifespan.

First Author  Duran-Ortiz S Year  2021
Journal  Aging Cell Volume  20
Issue  12 Pages  e13506
PubMed ID  34811874 Mgi Jnum  J:316835
Mgi Id  MGI:6841050 Doi  10.1111/acel.13506
Citation  Duran-Ortiz S, et al. (2021) Growth hormone receptor gene disruption in mature-adult mice improves male insulin sensitivity and extends female lifespan. Aging Cell 20(12):e13506
abstractText  Studies in multiple species indicate that reducing growth hormone (GH) action enhances healthy lifespan. In fact, GH receptor knockout (GHRKO) mice hold the Methuselah prize for the world's longest-lived laboratory mouse. We previously demonstrated that GHR ablation starting at puberty (1.5 months), improved insulin sensitivity and female lifespan but results in markedly reduced body size. In this study, we investigated the effects of GHR disruption in mature-adult mice at 6 months old (6mGHRKO). These mice exhibited GH resistance (reduced IGF-1 and elevated GH serum levels), increased body adiposity, reduced lean mass, and minimal effects on body length. Importantly, 6mGHRKO males have enhanced insulin sensitivity and reduced neoplasms while females exhibited increased median and maximal lifespan. Furthermore, fasting glucose and oxidative damage was reduced in females compared to males irrespective of Ghr deletion. Overall, disrupted GH action in adult mice resulted in sexual dimorphic effects suggesting that GH reduction at older ages may have gerotherapeutic effects.
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