Hallmarks of Aging Associate with High Intensity Interval Training Benefits and Frailty in Female C57Bl/6J Mice

Abstract Frailty and cognitive decline are common among older adults, increasing risks of disability and loss of independence. We have previously demonstrated in mice that short session (≤10 minute) high-intensity interval training (HIIT) is an effective intervention for frailty, but benefits for cognitive function and reducing hallmarks of aging have not been examined. Thus, we studied 24-month-old female C57BL/6J mice from our previous study that remained sedentary or performed a 10-minute HIIT regimen 3-days-a-week for 8 weeks. We found HIIT improved cognitive aspects including an increase in T-maze alternation % and novel object recognition, but no differences were observed in Barnes maze or light-dark preference. To explore HIIT impacts on the hallmarks of aging, we examined liver, gastrocnemius muscle, and cortex brain tissues for mitochondria expression, autophagy, cellular senescence, and telomere length. HIIT increased expression of mitochondrial complexes I and V, as well as PGC1α and SIRT3 in all tissues. Autophagy marker beclin was elevated across all tissues, while p62 was increased in liver and muscle but not in the cortex, and LC3-II was lower in muscle and liver. Senescence marker p16 was lower in HIIT muscle and liver, whereas p21 decreased in liver but increased in muscle. Telomere lengths were greater in liver, but no changes in muscle or cortex. Additionally, within the group of sedentary mice, we identified differences in hallmarks of aging that potentially underlie frailty as measured using different mouse frailty assessment tools. These results highlight the potential for multi-tissue geroprotective benefits of short session HIIT to reduce frailty and improve cognition for healthy aging.