A circadian rhythm-restricted diet regulates autophagy to improve cognitive function and prolong lifespan.

Diet and circadian rhythms have been found to have a profound impact on health, disease, and aging. Skipping breakfast, eating late, and overeating have adverse effects on the body's metabolism and increase the risk of cardiovascular and metabolic diseases. Disturbance of circadian rhythms has been associated with increased risk of atherosclerosis, Alzheimer's disease, Parkinson's disease, and other diseases. Abnormal deposition of amyloid β (Aβ) and tau proteins in the brain and impaired synaptic function are linked to cognitive dysfunction. A restrictive diet following the circadian rhythm can affect the metabolism of lipids, glucose, and amino acids such as branched chain amino acids and cysteine. These metabolic changes contribute to autophagy through molecular mechanisms such as adenosine monophosphate-activated protein kinase (AMPK), rapamycin (mTOR), D-β-hydroxybutyrate (D-BHB), and neuropeptide Y (NPY). Autophagy, in turn, promotes the removal of abnormally deposited proteins and damaged organelles and improves cognitive function, ultimately prolonging lifespan. In addition, a diet restricted to the circadian rhythm induces increased expression of brain-derived neurotrophic factor (BDNF) in the forebrain region, regulating autophagy and increasing synaptic plasticity, thus enhancing cognitive function. Consequently, circadian rhythm-restricted diets could serve as a promising non-pharmacological treatment for preventing and improving cognitive dysfunction and prolonging lifespan.