Senescent cell accumulation in white adipose tissue of growth hormone receptor antagonist transgenic mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 649-677-Adipocyte Biology
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-661
Ellen Richardson Lubbers*1, Yunhe Liu1, Tamara Tchkonia2, Tamar Pirtskhalava2, James L Kirkland2, John Joseph Kopchick1 and Darlene E Berryman1
1Ohio University, Athens, OH, 2Mayo Clinic, Rochester, MN
Generally, growth hormone (GH) action is negatively associated with longevity in many species. For example, GH receptor knockout (GHR-/-) mice are dwarf and obese, yet have improved insulin sensitivity and extended longevity, while bovine GH transgenic (bGH) mice are giant and lean, but have reduced insulin sensitivity and a shortened  lifespan. Interestingly, dwarf GH antagonist transgenic (GHA) mice are a unique exception to this trend.  Like GHR-/- mice, GHA mice are obese with  reduced GH action and decreased serum IGF-1 levels, , but do not experience improved insulin sensitivity and extended longevity as do most other mouse lines with reduced GH action.  Cellular senescence has been linked with many consequences of aging and several age-related diseases.  This has been suggested to be partially due to the inflammatory secretome of senescent cells.  While accumulation of senescent cells has not previously been measured in GHA mice, senescent cell accumulation in bGH and GHR-/- mice have been determined.  GHR-/- mice and bGH mice have decreased and increased accumulation of senescent cells in adipose tissue, respectively, leading to the hypothesis that senescent cell accumulation contributes to the lifespan changes in these mice. In this study, we investigate the accumulation of senescent cells and the expression of senescence associated genes in five adipose depots (two subcutaneous and three intra-abdominal) of GHA and WT mice. To determine the accumulation of senescent cells, tissue from 18 month old GHA mice and their WT controls was stained for senescence-associated-β-galactosidase (SA-β-gal) activity.  Percentages of SA- β-gal positive cells were determined by comparing phase and DAPI images of four different microscopic fields of each sample as used previously to assess senescent cells in bGH and GHR-/- adipose tissue.  The expression level of senescence-associated genes was determined by quantitative real time PCR. Interestingly, the GHA mice did not have reduced numbers of senescent cells in adipose tissue, as would be expected due to their low GH signaling.  Rather, the GHA mice had no significant difference in the numbers of senescent cells in most WAT depots, potentially contributing to a more inflammatory environment within the tissue than is observed in GHR-/- mice.  This increased inflammation, which is not seen in other models of reduced GH action, could contribute to the absence of an extended lifespan in GHA mice.

Nothing to Disclose: ERL, YL, TT, TP, JLK, JJK, DEB

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Sources of Research Support: This work was supported in part by the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by the AMVETS, by the Diabetes Institute at Ohio University, and by NIH grants DK083729, AG019899, AG031736.