Prior alcohol exposure limits aerobic exercise induced adaptations but does not accelerate markers of aging in UM-HET3 mice

BACKGROUND: Alcohol consumption in early adulthood is widespread and can lead to altered body composition, disrupted metabolism, and accelerated aging. Aerobic exercise has been shown to counteract some of the negative effects of alcohol consumption including minimizing lean muscle loss and muscle strength. Further, recent preliminary data from our laboratory suggests that aerobic exercise performed concurrently with alcohol consumption may improve longevity compared to alcohol use under sedentary conditions. The objective of this study was to determine whether exercise initiated later in life after cessation of alcohol intake could have similar beneficial effects or assist in the recovery of deficits caused by prior alcohol use. It is hypothesized that alcohol use in midlife will accelerate markers of aging and frailty and that a period of voluntary aerobic exercise training later in life will offset pre-existing alcohol-induced decrements. METHODS: At 7-8 months of age, female UM-HET3 mice were randomized into four groups: control sedentary (CON SED; n = 7), control exercise (CON EX; n = 7), alcohol sedentary (EtOH SED; n = 6), or alcohol exercise (EtOH EX; n=6). Lieber DeCarli liquid diet was used to deliver alcohol (EtOH) for 6 weeks after which, all animals resumed an alcohol-free chow diet. Exercise training was initiated ~6 months after the cessation of EtOH intake. Exercise groups were given 9 weeks of voluntary running wheel access. Testing of physical function and aging related markers were completed at various timepoints throughout the experiment. RESULTS: After 9 weeks of control or alcohol liquid diet, there were no significant differences between groups in lean mass, fat mass, and grip strength. During the voluntary wheel running period 6 months later, EtOH EX ran greater distances overall than CON EX. However, on the endurance run-to-fatigue test CON EX ran significantly longer than ETOH EX despite both groups having a significant drop in glucose pre to post run. CON EX also had greater elevations in blood ketone levels post-run. After 4 months of detraining and no wheel access, a second run-to-fatigue test was administered which showed no differences across groups. At 18 and 21 months of age, frailty was not different across the four groups. However, frailty scores increased across time indicating similar rates of aging across groups. CONCLUSION: Previous alcohol use prevents voluntary exercise induced adaptations in aerobic capacity as evidenced by shorter run time during a run to fatigue test. However, no differences in grip strength, lean mass or frailty scores have been noted in alcohol consuming groups indicating that the outbred UM-HET3 strain may be resistant to some of the commonly observed effects of alcohol on these indices of aging. This is important to note, as the UM-HET3 strain is the gold standard strain for interventional longevity testing. Future experiments will investigate the impact of alcohol and later life exercise on longevity. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.