Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice.

Michael B Stout,Edward O List,Carlos Escande,Richard A Miller,Ellen R Lubbers,Allyson K Palmer,Adam Spong,John J Kopchick,Darlene E Berryman,Michal M Masternak,Tamar Pirtskhalava,Andrzej Bartke,Tamara Tchkonia,Ann L Oberg,Nathan K Lebrasseur,James L Kirkland

doi:10.18632/aging.100681

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.

Highlights

Growth hormone (GH) plays a central role in regulating mammalian growth, metabolic homeostasis, and adiposity
Lipid redistribution frequently occurs in aging mammals [28], so delayed aging phenotypes could be associated with reduced lipid redistribution
We found that GH-deficient and -resistant mutants have preservation of extra-peritoneal White adipose tissue (WAT) at 18 months of age

Summary

Introduction

Growth hormone (GH) plays a central role in regulating mammalian growth, metabolic homeostasis, and adiposity. GH, either independently or through insulinlike growth factor-1 (IGF-1), has profound effects on age-related disease onset and longevity. Both mice and humans with excessive GH production have increased mortality rates compared to age-matched controls [1, 2], presumably due to higher incidence of metabolic dysfunction and cancer. Decreased GH activity is associated with dramatic lifespan extension in mice and similar effects in rats [3,4,5,6,7]. The effect of diminished GH activity on human lifespan is yet to be www.impactaging.com. Several different GH-related gene mutations elicit lifespan extension in mice, regardless of genetic background or diet administered [10]

Methods

Results

Conclusion