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Research Highlights

Could fasting reset the body’s clock and protect the brain against Alzheimer’s?

Restricting feeding times protected the brains of mice from some of the damage seen in Alzheimer’s disease and improved their ability to remember. The results of this NIA-funded study, published in Cell Metabolism, suggest that this type of fasting may help protect against Alzheimer’s by resetting the body’s internal clock and the brain’s genetic activity.

Overhead illustration of human brain with clock lying on it.

Circadian rhythms — the body’s internal clock — describe the physical, mental, and behavioral patterns of activity that follow a 24-hour cycle. Disturbance of circadian rhythms is common in people with Alzheimer’s and contributes to cognitive decline, confusion in the evening, and trouble falling and staying asleep. Research has shown that time-restricted feeding (TRF) — a form of intermittent fasting — may help reset circadian rhythms and improve sleep, digestion, and other health factors.

In this study, a research team led by scientists at the University of California, San Diego studied the effects of TRF on genetically engineered mice, which produce high levels of beta-amyloid, a protein that may appear in the brains of people with Alzheimer’s. These mice showed many of the signs of Alzheimer’s, including the presence of high levels of beta-amyloid plaques in key brain regions.

The scientists tested the effects of TRF by placing both control and Alzheimer’s mice on either a restricted diet — six hours’ feeding with 18 hours’ fasting — or on an unrestricted one.

Initial experiments showed that the circadian rhythms of the Alzheimer’s mice were disrupted and that TRF may restore some of them. For example, the Alzheimer’s mice that were fed restricted diets had fewer bouts of activity during sleep than the ones that ate freely. This lower activity pattern was similar to that seen in control mice that ate freely.

Further experiments showed that TRF reduced many of the signs of brain damage linked to Alzheimer’s. The brains of the Alzheimer’s mice that followed the restricted diet had lower levels of beta-amyloid plaques and reduced inflammatory activity. Similar results were seen in a separate line of Alzheimer’s mice that showed signs of the disease earlier than the group of Alzheimer’s mice referenced above.

Experiments in this separate line of Alzheimer’s mice also showed that TRF may improve cognition. Alzheimer’s mice fed a restricted diet remembered the locations of newly placed objects in mazes better than those fed unrestricted diets and at levels seen in control mice. Importantly, the mice in all groups ate the same volume of food, confirming that the observed changes were not due to calorie restriction.

Finally, genetic analysis of the brains of the first Alzheimer’s mice suggested that TRF reversed many of the changes associated with the disease. The genetic activity seen in the brains of Alzheimer’s mice fed a restricted diet looked similar to that of control mice and very different to that of Alzheimer’s mice on unrestricted diets.

Overall, these findings suggest that TRF may restore circadian rhythms and slow the behavioral, cognitive, and molecular disruptions associated with Alzheimer’s in mice. Additional research is needed to test the effects of TRF in people with the disease. Nonetheless, TRF may hold promise as a nonpharmacological strategy to reduce or halt Alzheimer’s progression.

This research was supported in part by NIA grants AG061831 and AG066596.

These activities relate to NIH’s AD+ADRD Research Implementation Milestone 8.B, “Increase investment in clinical trials that robustly test a variety of lifestyle and other non-pharmacological interventions.”

Reference:

Whittaker DS, et al. Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease. Cell Metabolism. 2023;35(10):1704-1721.e6. doi:10.1016/j.cmet.2023.07.014.

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