earticle

영어

Aging is accompanied by progressive impairments in mitochondrial bioenergetics, apoptosis regulation, and gut microbiota homeostasis, all of which contribute to cognitive decline. In this study, we investigat-ed whether the effects of treadmill exercise on the gut microbiota-mito-chondrion-neuronal plasticity axis differed between young (15 months) and old (28 months) mice. Male C57BL/6 mice were randomly assigned to the following groups: early sedentary, early exercise, late sedentary, or late exercise groups and completed an 8-week treadmill training protocol. Cognitive function was assessed using the passive avoidance test and the Morris water maze test. Hippocampal mitochondrial respi-ration, Ca²⁺ retention capacity, and Bax/Bcl-2 expression were quanti-fied, and the gut microbiota composition was analyzed using 16S ribo-somal RNA sequencing. Mice that did not exercise in old age exhibited memory impairment, decreased mitochondrial oxidative respiration, re-duced Ca²⁺ retention, increased Bax expression, decreased Bcl-2 lev-els, and decreased abundance of Lactobacillus, Bifidobacterium, and Akkermansia. Exercise significantly improved behavioral performance, mitochondrial function, and apoptosis balance, while also increasing beneficial gut microbiota. Notably, these effects were significantly greater in late-aged compared to early-aged mice. These results demonstrate that the efficacy of exercise in modulating the microbio-ta-mitochondrion-brain axis varies with age. Early-aged appears to rep-resent a more responsive biological period during which exercise is more effective in improving mitochondrial integrity, microbiota compo-sition, and cognitive resilience. These results suggest that initiating ex-ercise early in the aging process may maximize neuroprotective effects and delay age-related functional decline.