A Long-lived Mouse Lacking Both Growth Hormone and Growth Hormone Receptor: A New Animal Model for Aging Studies.
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.
College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando.|Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield.|Department of Oncological Endocrinology, Medical University of Lodz, Poland.
Adam
A
Gesing
College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando.|Department of Medical Biochemistry and Molecular Biology, University of Saarland, Homburg, Germany.|Department of Biotechnology, University of Applied Sciences Kaiserslautern, Zweibrücken, Germany.
Denise
D
Wiesenborn
College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando.|Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton.
Andrew
A
Do
College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando.|Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia.
Vinal
V
Menon
College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando.|Faculdade de Nutrição, Universidade Federal de Pelotas, Rio Grande do Sul, Brazil.
Augusto
A
Schneider
College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando.
Berta
B
Victoria
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota.
Michael B
MB
Stout
Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens.
John J
JJ
Kopchick
Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield.
Andrzej
A
Bartke
College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando.|Department of Head and Neck Surgery, The Greater Poland Cancer Centre, Poznan, Poland.
Michal M
MM
Masternak
D000375:Aging / Q000502:physiology*; D000818:Animals; D013006:Growth Hormone / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008017:Life Expectancy; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D011986:Receptors, Somatotropin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D007328:Insulin; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
Ames dwarf mice; Dwarfism; GHRKO mice; Insulin signaling; Longevity
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