Daytime‐Restricted Feeding Alleviates D‐Galactose‐Induced Aging in Mice and Regulates the AMPK and mTORC1 Activities

ABSTRACT Time‐restricted feeding (TRF) is a distinct regimen of intermittent fasting advocated for health improving. Although nighttime TRF (NRF) in rodents is analogous to daytime TRF (DRF) in humans and has health benefits, the effects of DRF on rodent's health remain uncertain. The adverse health effects of DRF in rodents are primarily attributed to its implementation‐induced temporal shift in the expression of circadian rhythm‐related genes. However, studies also demonstrate the health–beneficial effect of restricted feeding itself on metabolic homeostasis, particularly in periphery tissues. Moreover, the direct effects of DRF on aging progression in rodents are underexplored, highlighting a gap in current research. To explore the overall health effects of long‐term DRF in rodents, especially its influence on aging progression, we investigated the impact of long‐term DRF on mice under a progeric aging condition. Results showed that both 4‐h and 8‐h DRF regimens exerted positive effects on aging retardation; these effects were manifested as improved physical and memory capacities, enhanced liver and kidney functions, and reduced oxidative damage and inflammatory response. These DRF regimens also lowered the manifestation of aging‐related markers in peripheral tissues, with decreased SA‐β‐gal staining and p16 expression. Mechanistically, DRF regimens, especially DRF8, upregulated AMPK signaling and downregulated mTORC1 signaling. Interestingly, the health benefits of DRF are similar to those of metformin intervention. In conclusion, our study demonstrates for the first time that DRF effectively counteracts oxidative stress‐induced aging progression in mice, supporting the viewpoint that TRF as a promising strategy for preventing aging and aging‐related disorders.