Hesperidin Ameliorates Sarcopenia through the Regulation of Inflammaging and the AKT/mTOR/FoxO3a Signaling Pathway in 22–26-Month-Old Mice

Faced with a globally aging society, the maintenance of health and quality of life in older people is very important. The age-related loss of muscle mass and strength, known as sarcopenia, severely reduces quality of life and increases the risks of various diseases. In this study, we investigated the inhibitory effect of hesperidin (HES) on inflammaging, with the intention of evaluating its potential use as a treatment for sarcopenia. We studied 22–26-month-old mice, corresponding to humans aged ≥70 years, with aging-related sarcopenia, and young mice aged 3–6 months. The daily administration of HES for 8 weeks resulted in greater muscle mass and strength and increased the fiber size of the old mice. HES also restored the immune homeostasis that had been disrupted by aging, such as the imbalance in M1/M2 macrophage ratio. In addition, we found that HES ameliorated the sarcopenia by regulating AKT/mammalian target of rapamycin/forkhead box 3a signaling through an increase in insulin-like growth factor (IGF)-1 expression in the old mice. Therefore, HES represents a promising candidate inhibitor of sarcopenia in older people, and its effects are achieved through the maintenance of immune homeostasis.