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

Autor: Adekunbi DA; Texas Pregnancy and Life-Course Health Research Center, Department of Animal Science, University of Wyoming, Laramie, WY, USA., Li C; Texas Pregnancy and Life-Course Health Research Center, Department of Animal Science, University of Wyoming, Laramie, WY, USA., Nathanielsz PW; Texas Pregnancy and Life-Course Health Research Center, Department of Animal Science, University of Wyoming, Laramie, WY, USA., Salmon AB; Barshop Institute for Longevity and Aging Studies and Department of Molecular Medicine, The University of Texas Health Science Center At San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA. salmona@uthscsa.edu.; Geriatric Research Education and Clinical Center, Audie L. Murphy Hospital, Southwest Veterans Health Care System, San Antonio, TX, USA. salmona@uthscsa.edu.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2021 Aug; Vol. 43 (4), pp. 2067-2085. Date of Electronic Publication: 2021 Jun 05.
DOI: 10.1007/s11357-021-00395-1
Abstrakt: 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 (H 2 O 2 ), 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 H 2 O 2 (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.
(© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)
Databáze: MEDLINE
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