Abstract
Mutations Affecting Mammalian Aging: GH and GHR vs IGF-1 and Insulin.
Highlights
Reviewed by: Adam Salmon, The University of Texas Health Science Center at San Antonio, United States Jenny C
A report of extended longevity in mice homozygous for a mutation producing growth hormone (GH) deficiency (Brown-Borg et al, 1996) was quickly followed by the demonstration of extensive homology between one of the key longevity genes in a worm, Caenorhabditis elegans, and genes coding for insulin and insulin-like growth factor-1 (IGF-1) receptors in mammals (Kimura et al, 1997)
Since GH is the key determinant of hepatic IGF-1 expression and circulating IGF-1 levels, and has major impact on insulin signaling (Figure 1), these findings led to an exciting conclusion that the insulin/insulin-like growth factor signaling (IIS) is an evolutionarily conserved mechanism which controls aging in organisms ranging from yeast and worms to insects and mammals
Summary
Received: 12 February 2021 Accepted: 08 November 2021 Published: 24 November 2021. Citation: Bartke A and Brown-Borg H (2021) Mutations Affecting Mammalian Aging: GH and GHR vs IGF-1 and Insulin. Evidence for the ability of GH to influence healthspan and lifespan of laboratory mice is very strong and includes significant extension of longevity in both sexes of mice with hypopituitarism (combined deficiency of GH, prolactin, and TSH) (Brown-Borg et al, 1996; Flurkey et al, 2001), in mice with isolated GH deficiency due to mutation of Ghrhr gene or deletion of Ghrh (Flurkey et al, 2001; Sun et al, 2013), and in mice with GH resistance due to Ghr gene disruption (Zhou et al, 1997; Coschigano et al, 2003) This evidence for association of genetically reduced GH signaling with extended longevity was obtained in different laboratories and included animals with different genetic background (Bartke and Turyn, 2001; Coschigano et al, 2003; Aguiar-Oliveira and Bartke, 2019). In contrast to the remarkable extension of longevity in female and male mice lacking GH or GH receptors, the impact of reduced IGF-1 signaling on longevity of IGF1R ± mice and mice treated with an antibody to IGF-1 receptor is modest and seen only in one sex
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