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J Gerontol A Biol Sci Med Sci. 2017 Aug 1;72(8):1054-1061. doi: 10.1093/gerona/glw193.

A Long-lived Mouse Lacking Both Growth Hormone and Growth Hormone Receptor: A New Animal Model for Aging Studies.

Author information

1
College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando.
2
Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield.
3
Department of Oncological Endocrinology, Medical University of Lodz, Poland.
4
Department of Medical Biochemistry and Molecular Biology, University of Saarland, Homburg, Germany.
5
Department of Biotechnology, University of Applied Sciences Kaiserslautern, Zweibrücken, Germany.
6
Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton.
7
Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia.
8
Faculdade de Nutrição, Universidade Federal de Pelotas, Rio Grande do Sul, Brazil.
9
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota.
10
Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens.
11
Department of Head and Neck Surgery, The Greater Poland Cancer Centre, Poznan, Poland.

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.

KEYWORDS:

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

PMID:
27688483
PMCID:
PMC5861925
DOI:
10.1093/gerona/glw193
[Indexed for MEDLINE]
Free PMC Article

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