title: Disruption of the GH Receptor Gene in Adult Mice Increases Maximal Lifespan in Females.
abstract: GH and IGF-1 are important for a variety of physiological processes including growth, development, and aging. Mice with reduced levels of GH and IGF-1 have been shown to live longer than wild-type controls. Our laboratory has previously found that mice with a GH receptor gene knockout (GHRKO) from conception exhibit low rates of cancer, resistance to diet-induced diabetes, and extension of lifespan. The GHRKO mouse as well as other mouse lines with reduced GH action display low IGF-1 levels, smaller body size, increased adiposity, and increased longevity. To date, nearly all of these mouse strains carry germline mutations. Importantly, the effect of a long-term suppression of the GH/IGF-1 axis during adulthood, as would be considered for human therapeutic purposes, has not been tested. The goal of this study was to determine whether temporally controlled Ghr gene deletion in adult mice would affect metabolism and longevity. Thus, we produced adult-onset GHRKO (aGHRKO) mice by disrupting the Ghr gene at 6 weeks of age. We found that aGHRKO mice replicate many of the beneficial effects observed in long-lived GHRKO mice. For example, aGHRKO mice, like GHRKO animals, displayed retarded growth and high adiposity with improved insulin sensitivity. Importantly, female aGHRKO animals showed an increase in their maximal lifespan, whereas the lifespan of male aGHRKO mice was not different from controls.
authors.affiliation: Edison Biotechnology Institute (R.K.J., S.D.-O., O..S., E.G.S., D.E.B., E.O.L., J.J.K.), Ohio University, Athens, Ohio 45701; Department of Biological Sciences (S.D.-O., E.G.S., J.J.K.), Ohio University, Athens, Ohio 45701; and Department of Biomedical Sciences (D.E.B., J.J.K.), Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
authors.forename: Riia K
authors.initials: RK
authors.lastname: Junnila
authors.affiliation: Edison Biotechnology Institute (R.K.J., S.D.-O., O..S., E.G.S., D.E.B., E.O.L., J.J.K.), Ohio University, Athens, Ohio 45701; Department of Biological Sciences (S.D.-O., E.G.S., J.J.K.), Ohio University, Athens, Ohio 45701; and Department of Biomedical Sciences (D.E.B., J.J.K.), Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
authors.forename: Silvana
authors.initials: S
authors.lastname: Duran-Ortiz
authors.affiliation: Edison Biotechnology Institute (R.K.J., S.D.-O., O..S., E.G.S., D.E.B., E.O.L., J.J.K.), Ohio University, Athens, Ohio 45701; Department of Biological Sciences (S.D.-O., E.G.S., J.J.K.), Ohio University, Athens, Ohio 45701; and Department of Biomedical Sciences (D.E.B., J.J.K.), Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
authors.forename: Ozan
authors.initials: O
authors.lastname: Suer
authors.affiliation: Edison Biotechnology Institute (R.K.J., S.D.-O., O..S., E.G.S., D.E.B., E.O.L., J.J.K.), Ohio University, Athens, Ohio 45701; Department of Biological Sciences (S.D.-O., E.G.S., J.J.K.), Ohio University, Athens, Ohio 45701; and Department of Biomedical Sciences (D.E.B., J.J.K.), Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
authors.forename: Elahu G
authors.initials: EG
authors.lastname: Sustarsic
authors.affiliation: Edison Biotechnology Institute (R.K.J., S.D.-O., O..S., E.G.S., D.E.B., E.O.L., J.J.K.), Ohio University, Athens, Ohio 45701; Department of Biological Sciences (S.D.-O., E.G.S., J.J.K.), Ohio University, Athens, Ohio 45701; and Department of Biomedical Sciences (D.E.B., J.J.K.), Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
authors.forename: Darlene E
authors.initials: DE
authors.lastname: Berryman
authors.affiliation: Edison Biotechnology Institute (R.K.J., S.D.-O., O..S., E.G.S., D.E.B., E.O.L., J.J.K.), Ohio University, Athens, Ohio 45701; Department of Biological Sciences (S.D.-O., E.G.S., J.J.K.), Ohio University, Athens, Ohio 45701; and Department of Biomedical Sciences (D.E.B., J.J.K.), Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
authors.forename: Edward O
authors.initials: EO
authors.lastname: List
authors.affiliation: Edison Biotechnology Institute (R.K.J., S.D.-O., O..S., E.G.S., D.E.B., E.O.L., J.J.K.), Ohio University, Athens, Ohio 45701; Department of Biological Sciences (S.D.-O., E.G.S., J.J.K.), Ohio University, Athens, Ohio 45701; and Department of Biomedical Sciences (D.E.B., J.J.K.), Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
mesh_terms: D050154:Adiposity / Q000235:genetics; D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone