The journals of gerontology. Series A, Biological sciences and medical sciencesSep 25, 2026

Signs of Aging Linked to Benefits from High-Intensity Interval Training and Frailty in Female Mice

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 26, 2026

Abstract

High-intensity interval training (HIIT) for 10 minutes, three times a week, improved cognitive function in 24-month-old female mice.

HIIT led to increased performance in T-maze alternation and novel object recognition tests, indicating enhanced cognitive abilities.
No differences in cognitive function were observed in Barnes maze or light-dark preference tests after HIIT.
HIIT increased the expression of mitochondrial complexes I and V, PGC1α, and SIRT3 across liver, muscle, and brain tissues.
Autophagy markers showed variable changes, with beclin elevated in all tissues, while p62 increased in liver and muscle but not in the cortex.
Senescence markers p16 and p21 exhibited reduced levels in liver and muscle tissues following HIIT.
Telomere lengths were found to be greater in the liver of HIIT mice, with no significant changes in muscle or cortex.

Simplified

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.

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Signs of Aging Linked to Benefits from High-Intensity Interval Training and Frailty in Female Mice

Abstract

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