Author Identifier (ORCID)
Ajish Ariyath: https://orcid.org/0000-0003-1611-2990
Zoe Mputhia: https://orcid.org/0000-0003-0045-7134
W. M.A.D.Binosha Fernando: https://orcid.org/0000-0002-8364-7808
Samantha Gardener: https://orcid.org/0000-0002-1933-5260
Stephanie R. Rainey-Smith: https://orcid.org/0000-0001-7328-9624
Ralph Martins: https://orcid.org/0000-0002-4828-9363
Prashant Bharadwaj: https://orcid.org/0000-0003-4361-9906
Abstract
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.
Keywords
Alzheimer's disease, amyloid beta protein, amyloid precursor protein, autophagy, calorie restriction, diet, exercise, fasting, lifestyle interventions, physical activity, sleep, sleep deprivation, sleep fragmentation
Document Type
Journal Article
Date of Publication
2-1-2026
Volume
22
Issue
2
PubMed ID
41724666
Publication Title
Alzheimer's & Dementia
Publisher
Wiley
School
Centre of Excellence for Alzheimer's Disease Research and Care / Sarich and Patricia Neuroscience Research Institute / School of Medical and Health Sciences
Funders
National Health and Medical Research Council / Australian Research Council / National Foundation for Medical Research and Innovation
Grant Number
ARC Number : APP1107109
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Ariyath, A., Mputhia, Z., Dougherty, C., Rahuman, B. K., Fernando, W. M. a. D. B., Brown, B., Gardener, S. L., Rainey‐Smith, S. R., Martins, R., & Bharadwaj, P. (2026). Regulation of autophagy‐mediated pathways by diet, physical activity, and sleep in Alzheimer’s disease. Alzheimer’s & Dementia, 22(2), e71191. https://doi.org/10.1002/alz.71191