Age and sex modify cellular proliferation responses to oxidative stress and glucocorticoid challenges in baboon cells

Abstract

Aging is associated with progressive loss of cellular homeostasis resulting from intrinsic and extrinsic challenges. Lack of a carefully designed, well-characterized, precise, translational experimental model is a major limitation to understanding the cellular perturbations that characterize aging. Here, we tested the feasibility of primary fibroblasts isolated from nonhuman primates (baboons) as a model of cellular resilience in response to homeostatic challenge. Using a real-time live-cell imaging system, we precisely defined a protocol for testing effects of prooxidant compounds (e.g., hydrogen peroxide (H2O2), paraquat), thapsigargin, dexamethasone, and a low glucose environment on cell proliferation in fibroblasts derived from baboons across the life course (n = 11/sex). Linear regression analysis indicated that donor age significantly reduced the ability of cells to proliferate following exposure to H2O2 (50 and 100µM) and paraquat (100 and 200µM) challenges in cells from males (6.4-21.3years; average lifespan 21years) but not cells from females (4.3-15.9years). Inhibitory effects of thapsigargin on cell proliferation were dependent on challenge duration (2 vs 24h) and concentration (0.1 and 1µM). Cells from older females (14.4-15.9years) exhibited greater resilience to thapsigargin (1µM; 24h) and dexamethasone (500µM) challenges than did those from younger females (4.3-6.7years). The cell proliferation response to low glucose (1mM) was reduced with age in both sexes. These data indicate that donor's chronological age and sex are important variables in determining fibroblast responses to metabolite and other challenges.