Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease

Alzheimer's disease (AD) is a progressive, age-related, neurodegenerative disorder marked by cognitive decline, memory loss, and accumulation of amyloid beta (Aβ) plaques and tau tangles. A key feature of AD is impaired protein homeostasis, often driven by autophagy dysfunction. Autophagy, a cellular degradation and recycling process, plays a vital role in maintaining neuronal health and is increasingly recognized as a therapeutic target in AD. Lifestyle factors such as diet, physical activity, and sleep can positively influence autophagy and support cognitive function. Intermittent fasting (IF) and calorie restriction (CR) activate autophagy and promote longevity; physical activity enhances cerebral blood flow and neurotrophic signaling; and adequate sleep supports autophagic processes, while sleep deprivation disrupts them. However, excessive autophagy may be detrimental. Understanding how lifestyle modulates autophagy is essential for developing non-pharmacological strategies to delay or prevent AD. This review explores the mechanistic links between autophagy and lifestyle interventions to support brain health in aging.