European Journal of Applied Physiology · Oct 24, 2026

High-intensity interval training modulates the SIRT1-P16 pathway, inflammatory markers, and oxidative stress in the liver of D-galactose-treated male rats

By Shahouzehi B, Jafari H, Rostamzadeh F

PURPOSE: Aging contributes to progressive hepatic dysfunction, characterized by increased oxidative stress, chronic inflammation, and mitochondrial impairment, which collectively exacerbate metabolic decline. This study examined the effects of high-intensity interval training (HIIT) on the SIRT1-P16 axis, oxidative stress, and inflammatory markers in a D-galactose (D-gal )-induced aging model in male Wistar rats. METHODS: Twenty-eight rats were assigned to four groups: Control (CTL), HIIT, D-gal, and D-gal+HIIT. Aging model was induced via daily subcutaneous injections of D-galactose (150 mg/kg) for eight weeks, while HIIT was performed on a treadmill five times per week over the same period. Gene expression and protein levels were measured by Real-time PCR and Western blot, respectively. Antioxidant and oxidant, and inflammatory markers were determined via colorimetric and ELISA methods. RESULTS: Gene expression analysis showed that D-gal significantly downregulated the expression of AMPK, SIRT1, and PGC-1α, whereas HIIT was associated with increased expression of these markers. Western blot analysis confirmed a reduction and elevation in SIRT1 and P16 protein, respectively, in the D-gal group, which were reversed following HIIT. HIIT also ameliorated the increase in the levels of malondialdehyde, IL-1β, IL-6, and TNF-α and the decrease in the SOD and GPx activities. CONCLUSION: Concurrent HIIT attenuated D-galactose-induced hepatic molecular and biochemical alterations associated with aging. These effects were accompanied by changes in SIRT1-P16-related markers, improved redox balance, and reduced inflammatory responses, supporting the potential of HIIT as a non-pharmacological strategy for promoting liver health during aging.

doi.org/10.1007/s00421-026-06484-3PubMed 42926221Interventions