Effects of chrononutrition on aging and lifespan

Chrononutrition is emerging as a focus in aging. Here, we describe the principal chrononutritional protocols and their effects on aging and lifespan by reviewing evidence derived from human cross-sectional and cohort studies, as well as from a range of animal models. Time-restricted eating/feeding (4-12 h window)，alternate-day fasting, and 5:2 diet have shown potential to improve cardiometabolic health and healthspan metrics in preclinical studies and clinical trials. However, observational studies reported a U-shaped pattern relationship between eating window duration and mortality risk and biological aging, with an elevated risk of ≤8 h windows. Aligning the intake of specific nutrients-such as carbohydrates, proteins, and antioxidants-with the circadian phase further optimizes health. We also discuss the side effect of irregular meals, breakfast skipping, late-evening intake and high meal frequency on aging-related disease and mortality risk. We highlight that circadian clock, nutrient-sensing pathways, and the gut microbiota could be involved in these processes. However, the precise molecular mechanisms through which these feeding patterns reinforce circadian clocks and confer systemic benefits are only beginning to be unraveled. In conclusion, translating chrononutrition from bench to population-level strategies remains a critical step toward promoting healthy aging.