title: Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice.
abstract: The aging process is associated with the development of several chronic diseases. White adipose tissue (WAT) may play a central role in age-related disease onset and progression due to declines in adipogenesis with advancing age. Recent reports indicate that the accumulation of senescent progenitor cells may be involved in age-related WAT dysfunction. Growth hormone (GH) action has profound effects on adiposity and metabolism and is known to influence lifespan. In the present study we tested the hypothesis that GH activity would predict age-related WAT dysfunction and accumulation of senescent cells. We found that long-lived GH-deficient and -resistant mice have reduced age-related lipid redistribution. Primary preadipocytes from GH-resistant mice also were found to have greater differentiation capacity at 20 months of age when compared to controls. GH activity was also found to be positively associated with senescent cell accumulation in WAT. Our results demonstrate an association between GH activity, age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further studies are needed to determine if GH is directly inducing cellular senescence in WAT or if GH actions on other target organs or alternative downstream alterations in insulin-like growth factor-1, insulin or glucose levels are responsible.
authors: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
authors: Michael B
authors: MB
authors: Stout
authors: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
authors: Tamara
authors: T
authors: Tchkonia
authors: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
authors: Tamar
authors: T
authors: Pirtskhalava
authors: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
authors: Allyson K
authors: AK
authors: Palmer
authors: Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA;
authors: Edward O
authors: EO
authors: List
authors: Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA;
authors: Darlene E
authors: DE
authors: Berryman
authors: Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA;
authors: Ellen R
authors: ER
authors: Lubbers
authors: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA;
authors: Carlos
authors: C
authors: Escande
authors: Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA;
authors: Adam
authors: A
authors: Spong
authors: Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA;
authors: Michal M
authors: MM
authors: Masternak
authors: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA;
authors: Ann L
authors: AL
authors: Oberg
authors: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA;
authors: Nathan K
authors: NK
authors: LeBrasseur
authors: Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Richard A
authors: RA
authors: Miller
authors: Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA;
authors: John J
authors: JJ
authors: Kopchick
authors: Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA;
authors: Andrzej
authors: A
authors: Bartke
authors: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
authors: James L
authors: JL
authors: Kirkland
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology / Q000503:physiopathology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D016922:Cellular Senescence / Q000502:physiology*; D013006:Growth Hormone / Q000494:pharmacology*; D050356:Lipid Metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D012333:RNA, Messenger
chemical_list: D012333:RNA, Messenger; D013006:Growth Hormone