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

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 100 µM) and paraquat (100 and 200 µM) challenges in cells from males (6.4-21.3 years; average lifespan 21 years) but not cells from females (4.3-15.9 years). Inhibitory effects of thapsigargin on cell proliferation were dependent on challenge duration (2 vs 24 h) and concentration (0.1 and 1 µM). Cells from older females (14.4-15.9 years) exhibited greater resilience to thapsigargin (1 µM; 24 h) and dexamethasone (500 µM) challenges than did those from younger females (4.3-6.7 years). The cell proliferation response to low glucose (1 mM) 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.