Fasting is required for many of the benefits of calorie restriction in the 3xTg mouse model of Alzheimer’s disease
Caloric restriction slows or prevents Alzheimer's disease in animal models. Calorie restriction is typically implemented in rodents through feeding once per day; as the animals quickly consume their food, they are subject to a prolonged self-imposed fasting period between meals. Here, we examine the distinct contributions of fasting and reduced calories to the beneficial effects of calorie restriction on Alzheimer's disease by placing male and female 3xTg and non-transgenic control mice on a series of diet regimens enabling us to dissect the effects of calories and fasting. We find that reducing calories alone improves body weight and glucose tolerance. However, a prolonged fast between meals is necessary for many of the benefits of calorie restriction, including improved insulin sensitivity, reduced Alzheimer's pathology, improved neuroprotective signaling, and improved cognition. Overall, our results suggest that both when and how much we eat may influence the development and progression of Alzheimer's disease.
Authors
- Jessica Han (ORCID: https://orcid.org/0000-0002-5823-9079)
- Michael J. Rigby (ORCID: https://orcid.org/0000-0001-8809-2648)
- Dudley W. Lamming (ORCID: https://orcid.org/0000-0002-0079-4467)
- Cara L. Green (ORCID: https://orcid.org/0000-0002-2293-9364)
- Michelle M. Sonsalla (ORCID: https://orcid.org/0000-0001-8493-1416)
- Reji Babygirija (ORCID: https://orcid.org/0000-0003-3719-5991)
- Mariah F. Calubag (ORCID: https://orcid.org/0000-0003-4843-3668)
- John M. Denu (ORCID: https://orcid.org/0000-0001-9415-0365)
- Luigi Puglielli (ORCID: https://orcid.org/0000-0003-0259-8424)
- David A. Harris (ORCID: https://orcid.org/0000-0001-5588-1632)
- Chung‐Yang Yeh (ORCID: https://orcid.org/0000-0002-0970-1300)
- Julia Illiano
- Ryan Matoska
- Isaac Grunow
- Diana Vertein
- Yang Liu (ORCID: https://orcid.org/0000-0002-5472-6080)
- Anna Tobon
- Sophia Schlorf
Institutions
- University of Wisconsin System (US)
- University of Wisconsin–Madison (US)
- University of Wisconsin Carbone Cancer Center (US)
- Institute on Aging (US)
- William S. Middleton Memorial Veterans Hospital (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-04
- DOI
- https://doi.org/10.1038/s41467-025-62416-3
- Citations
- 4
- Primary Topic
- Dietary Effects on Health
- Type
- article
- Field-Weighted Citation Impact
- 4.66
Funders
- U.S. Department of Veterans Affairs
- Alzheimer's Association
- Glenn Foundation for Medical Research
- University of Wisconsin Carbone Cancer Center
- Fondation pour la Recherche Médicale
- National Institutes of Health
- School of Medicine and Public Health, University of Wisconsin-Madison
- National Institute on Aging
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- Department of Surgery