Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer's disease
Whittaker DS, Akhmetova L, Carlin D, Romero H, Welsh DK, Colwell CS, Desplats P
Cell metabolism · 113 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- Thailand Research Fund
- Government
- National Institutes of Health
- University or hospital
- University of California, San Diego
- Government
- National Institute on Aging
- Government
- National Institute of Neurological Disorders and Stroke
- Government
- NINDS NIH HHS
- Government
- NIA NIH HHS
- Government
- NIH
- Grants
- National Institute of Neurological Disorders and Stroke (P30 NS 047101); National Institute on Aging (P30AG062429); National Institute on Aging (AG061831); National Institute on Aging (RF1 AG061831); University of California, San Diego (P30 NS047101); National Institute on Aging (T32 AG066596); National Institute of Neurological Disorders and Stroke (T32 NS061847); National Institute on Aging (5T32AG066596-02)
Based on 8 listed funder(s).
Publication
- Published
- 2023-08-21 · Cell Metab · vol. 35 · issue 10 · pp. 1704–1721.e6
- Publisher
- Cell Press
- Cited
- 151 citations · more than 100% of similar papers · 20.8× the field average
- Impact
- Top 10% most cited in its field
- References
- 96 works
- Access
- Open access (hybrid journal) · CC-BY-NC-ND
- Research areas
- Dietary Effects on Health · Circadian rhythm and melatonin · Genetics, Aging, and Longevity in Model Organisms
- Keywords
- Circadian rhythm, Neuroscience, Disease, Alzheimer's disease, Biology, Medicine, Internal medicine
- MeSH
- brain, animals, mice, transgenic, humans, mice, alzheimer disease, disease models, animal, circadian rhythm, amyloid beta-peptides
7 authors
From US
- Daniel S. WhittakerUniversity of California San Diego
- Laila AkhmetovaUniversity of California San Diego
- Daniel E. CarlinUniversity of California San Diego
- Haylie K. RomeroUniversity of California San Diego
- David K. WelshUniversity of California San Diego; VA San Diego Healthcare System
- Christopher Scott ColwellUniversity of California, Los Angeles; Neurobehavioral Systems
Abstract
Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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