A Long-Lived Mouse Lacking Both Growth Hormone And Growth Hormone Receptor: A New Animal Model For Aging Studies

Keywords

Ames dwarf mice; Dwarfism; GHRKO mice; Insulin signaling; Longevity

Abstract

Disruption of the growth hormone (GH) signaling pathway promotes insulin sensitivity and is associated with both delayed aging and extended longevity. Two kinds of long-lived mice-Ames dwarfs (df/df) and GH receptor gene-disrupted knockouts (GHRKO) are characterized by a suppressed GH axis with a significant reduction of body size and decreased plasma insulin-like growth factor-1 (IGF-1) and insulin levels. Ames dwarf mice are deficient in GH, prolactin, and thyrotropin, whereas GHRKOs are GH resistant and are dwarf with decreased circulating IGF-1 and increased GH. Crossing Ames dwarfs and GHRKOs produced a new mouse line (df/KO), lacking both GH and GH receptor. These mice are characterized by improved glucose tolerance and increased adiponectin level, which could imply that these mice should be also characterized by additional life-span extension when comparing with GHRKOs and Ames dwarfs. Importantly, our longevity experiments showed that df/KO mice maintain extended longevity when comparing with N control mice; however, they do not live longer than GHRKO and Ames df/df mice. These important findings indicate that silencing GH signal is important to extend the life span; however, further decrease of body size in mice with already inhibited GH signal does not extend the life span regardless of improved some health-span markers.

Publication Date

8-1-2017

Publication Title

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volume

72

Issue

8

Number of Pages

1054-1061

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1093/gerona/glw193

Socpus ID

85026861697 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85026861697

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