Effect of midlife exercise on lipid metabolism in aging mice: comparable to lifelong exercise, better than ceasing midlife exercise

This study examines the effects of continuous versus interrupted lifelong exercise on lipid metabolism in naturally aging male BALB/c mice. Five-week-old male BALB/c mice were randomly assigned to five groups: young control group (YC), natural ageing control group (AC), exercise cessation group (DE), middle-aged commencing exercise group (ME), and lifelong exercise group (LE). Moderate Intensity Continuous Training exercise sessions were conducted three times per week, with each session lasting 50 min; after exercise interventions until 72 weeks of age, the following parameters were measured: body morphology, exercise capacity, blood lipid, liver fat content, liver function, expression of liver lipid metabolism-related genes and endoplasmic reticulum stress-related genes, and activities of liver metabolism enzymes. The results suggest that advancing age leads to disrupted lipid processing, reduced hepatic performance, and increased endoplasmic reticular tension. Compared with the AC group, the ME and LE cohorts showed reduced serum lipids, whereas the LE group exhibited elevated high-density lipoprotein cholesterol (HDL-C) levels (P < 0.05). Post-exercise reductions were observed in hepatic total cholesterol and free fatty acid (FFA). Moreover, the exercises mitigated age-related hepatic impairments and diminished susceptibility towards cirrhosis despite higher aspartate aminotransferase (AST) and lower albumin (ALB) levels being evident within the DE cohort (P < 0.05). Exercise demonstrates the potential to mitigate age-related abnormalities in lipid metabolism. Middle-aged commencing and lifelong exercise interventions are more effective in alleviating lipid abnormalities than exercise cessation in middle age. This disparity in efficacy can be attributed to differences in regulating endoplasmic reticulum stress, enhancing liver lipid oxidation capacity, and reducing lipid synthesis ability. Notably, middle-aged individuals commencing exercise yield similar outcomes in regulating aging-associated abnormal lipid metabolism compared to the lifelong exercise group. This highlights the importance of initiating exercise in middle age, as it remains beneficial even if lifelong commitment is unfeasible, so exercise initiation in midlife is still beneficial. However, to prevent liver lipid metabolism disorders later in life, the earlier exercise initiation, the better.