Fisetin, a potential caloric restriction mimetic, attenuates senescence biomarkers in rat erythrocytes

An imbalanced redox status is a hallmark of the aging process. Caloric restriction mimetics (CRMs) are compounds that produce caloric restriction benefits at the molecular, cellular, and physiological level, translating into health-promoting effects. Fisetin is the least explored CRM, and its role in modulating oxidative stress during aging is not clearly known. This study investigated the antioxidative and protective potential of fisetin in a rat model of d-galactose (D-gal)-induced accelerated senescence, and in naturally aged rat erythrocytes. Young rats (4 months), aged D-gal-induced rats [24 months; 500 mg/kg body mass (b.m.); subcutaneous injection] and naturally aged D-gal-induced rats [24 months; 500 mg/kg b.m.; subcutaneous injection] were supplemented with fisetin (15 mg/kg b.m.; orally) for 6 weeks. The resulting data indicated that supplementation with fisetin suppresses aging-induced increases in the levels of reactive oxygen species, eryptosis, lipid peroxidation, and protein oxidation. Our data also show that fisetin significantly increases the levels of antioxidants and activates the plasma membrane redox system. Taken together, the findings show that a fisetin-rich diet could be an anti-aging intervention strategy.