Impact of 12-Week Moderate-Intensity Aerobic Training on Inflammasome Complex Activation in Elderly Women

Front Physiol. 2022 Feb 22:13:792859. doi: 10.3389/fphys.2022.792859. eCollection 2022.

Abstract

Aging often associates with a chronic low-grade inflammatory status that can be consequent to the activation of Toll-like receptors (TLRs) and the downstream NLR family pyrin domain containing 3 (NLRP3) inflammasome and causes a chronic secretion of pro-inflammatory cytokines. Since exercise has known anti-inflammatory effects, we investigated the effect of Nordic walking training on inflammasome activation and downstream effectors in elderly women. A population of elderly women was divided into EXP (n = 29) that completed 12 weeks of the moderate-intensity aerobic training program and CTRL (n = 29), performing no activity. Blood samples were taken before and after the first (T1-pre and T1-post, respectively) and last (T2-pre and T2-post, respectively) exercise unit. Inflammasome activation status was assessed by whole blood NLRP3 and TLR4 expression by RT-qPCR. Serum levels of IL-1β, IL-6, TNFα, and IL-18 cytokines were assayed by multiplex fluorescent beads-based immunoassays or ELISA. NLRP3 and TLR4 levels were reduced 2 folds between T1-pre and T2-pre and induced at T2-post, compared to T2-pre, by 2.6- and 2.9-fold, respectively. A single exercise bout elicited a 1. 38-, 1. 5-, and 1.36-fold rise of IL-1β, TNFα, and IL-6 concentration, respectively, although not significant, at the beginning of the training (T1-pre vs. T1-post), a 1.4-fold decrease for IL-1β and TNFα at the end of the training (T1-pre vs. T2-pre), and a 2-, 1.8- and 1.26-fold increase after the last exercise session (T2-pre vs. T2-post) for the three cytokines. When stratifying the population based on BMI in normal weight (NW) and overweight (OW), NLRP3 and TLR4 expression was affected only in NW. As for inflammatory cytokines, IL-1β was modulated in NW at the beginning of the training, whereas in OW at the end of the training; for TNFα, this time-dependent modulation was significant only in OW. Applied aerobic training affected the resting expression of inflammasome constituents (NLRP3 and TLR4) and levels of downstream effectors (IL-1β, TNFα, and IL-6). However, at the end of the program, participants acquire an acute inflammatory response to exercise that was absent at baseline. Future studies would have to define the molecular mechanisms associated with, and how to potentiate, the exercise-associated inflammatory response.

Keywords: NLRP3 inflammasome; aerobic exercise; aging; physical activity; pro-inflammatory cytokines.