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

Silvana Duran-Ortiz, Edward O. List, Yuji Ikeno, Jonathan Young, Reetobrata Basu, Stephen Bell, Todd McHugh, Kevin Funk, Samuel Mathes, Yanrong Qian, Prateek Kulkarni, Shoshana Yakar, Darlene E. Berryman, John J. Kopchick

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere13506
JournalAging cell
Volume20
Issue number12
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Cre-Lox
  • IGF-1
  • aging
  • growth hormone
  • insulin sensitivity
  • lifespan
  • tamoxifen

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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