Intermittent fasting applied in combination with astaxanthin alleviates D‐galactose‐induced aging in rats: Comparison in oxidative stress, immune response, and metabolomics

Effective anti-aging strategies involving dietary restriction and antioxidant supplementation are gaining increasing research attention, while the health effects of their combined intervention are rarely reported. In this study, for the first time, we investigated the anti-aging effects and underlying mechanisms of intermittent fasting (IF), astaxanthin (AX), and their combination in D-galactose-induced aging rats. Our results demonstrated that these three treatments effectively inhibited malondialdehyde levels and improved the activity of endogenous antioxidant enzymes in the brain, liver, and serum of aging rats. Simultaneously, the combination of IF and AX had a synergistic effect on the recovery of brain mitochondrial injury as evidenced by permeability transition pore openness, membrane potential, respiratory chain complex enzyme activity, and cortical and hippocampal lesions. Notably, the combination significantly increased the levels of Immunoglobulin M (55.66 ± 3.23%), immunoglobulin G (34.41 ± 2.65%), and IL-2 (23.49 ± 1.78%) compared with the model group. Moreover, AX reduced the accumulation of pro-inflammatory factor IL-6 (23.06 ± 2.02%), while the combination induced more remarkable reduction in the accumulation of IL-1β (35.92 ± 3.06%) in the serum. Considering the serum metabolomics analysis, we hypothesized that IF and AX played a positive role in the regulation of the nervous system, which was associated with the differential metabolites lysope 16:0, N-Acety-L-tyrosine, and L-Alanyl-L-Lysine. This research reveals that the combination therapy provided synergistic anti-aging efficacy by enhancing resistance to oxidative stress, ameliorating mitochondrial dysfunction, and restoring the immune system. These findings might have significant implications for further studies on the exploration of effective anti-aging therapy.