Nature sub-issue: Yuan Zengzheng/Cao Ruiyuan team reveals that intermittent fasting can prevent Alzheimer's disease

Alzheimer's disease (AD), commonly known as "Alzheimer's disease", is a serious neurodegenerative disease, patients usually appear with memory loss, weakened learning ability symptoms, accompanied by emotional regulation disorders and loss of exercise ability, greatly affecting the development of
individuals, families and even society.

Currently, about 50 million people worldwide suffer from Alzheimer's disease
.
As human life expectancy increases and aging society intensifies, the prevalence of Alzheimer's disease is also rising, and it is expected that by 2050, the number of Alzheimer's disease patients will increase to more than
150 million.

In the past few decades, the mainstream view has been that the cause of Alzheimer's disease is β-amyloid (Aβ) and Tau protein deposition, which causes a large number of neuronal deaths
.
However, treatments targeting these two targets have been largely unsuccessful, suggesting that Alzheimer's disease is a complex multifactorial disease influenced by factors such as environment and lifestyle, involving multiple metabolic pathways
from the periphery to the brain.

On November 17, 2022, Yuan Zengzheng, Cao Ruiyuan and others of the Institute of Military Medical Research published a report in Nature Aging: Intermittent fasting protects against Alzheimer's disease in mice by altering metabolism through remodeling Research paper of the gut microbiota.

The study showed that intermittent fasting (IF) improved cognitive function and Alzheimer's disease-like pathology
in a mouse model of Alzheimer's disease (5XFAD).

Intermittent fasting (IF) is a popular method of dietary restriction, that is, alternating fasting and eating, and many studies have found that intermittent fasting is not only effective in weight loss, but also promotes metabolism, improves physical health and sleep quality
.
There are also many studies that show that intermittent fasting can prolong life
.

Recent studies have shown that intermittent fasting has a good protective effect
against neurodegenerative diseases including Parkinson's disease and Huntington's disease.

In addition, there is multiple pieces of evidence that intermittent fasting improves Alzheimer's disease outcomes
by reducing Alzheimer's disease-related pathologies and cognitive impairments in various models of Alzheimer's disease.
However, the specific mechanisms by which intermittent fasting improves Alzheimer's disease remain poorly
understood.

There are some studies that have revealed a correlation
between Alzheimer's disease pathology and intestinal dysbacteriosis.
Changes in gut microbiota composition and diversity were observed in both mouse models of Alzheimer's disease and human Alzheimer's disease patients compared to healthy controls
.

In different mouse models of Alzheimer's disease, altering their gut microbiota composition and diversity with antibiotics or probiotics can reduce the neuroinflammatory β-amyloid (Aβ) burden
.
Intestinal microbiota transplantation in healthy mice was able to improve Alzheimer's disease-like lesions
in mouse models of Alzheimer's disease.

These studies suggest that gut microbiota is a potential therapeutic target for Alzheimer's
disease.

Interestingly, there is growing evidence that intermittent fasting is able to significantly protect against several diseases, including obesity, autoimmune diseases, and diabetes
, by regulating the composition of the gut microbiota and its metabolism.

Given the correlation between gut microbiota and Alzheimer's disease, and the potential regulatory effect of intermittent fasting on the gut microbiota, the research team explored the mechanism
of action of the microbiome-gut-brain signaling axis in the effects of intermittent fasting on Alzheimer's disease.

Intermittent fasting changes the composition of the intestinal flora, allowing probiotics such as lactic acid bacteria to be significantly enriched
.
Changes in the composition of the intestinal flora affect metabolic activity and the production
of metabolites.
Metabolomic analysis showed that intermittent fasting led to decreased carbohydrate metabolism (e.
g.
, glucose) and increased
levels of amino acids such as sar and dimethylglycine (DMG).
The study also found that sarcosine, or dimethylglycine, with elevated intermittent fasting, mimicked the protective effects of intermittent fasting in a mouse model of Alzheimer's disease, including improved cognitive decline, Aβ burden, and glial overactivation
.

In a mouse model of Alzheimer's disease, intermittent fasting attenuates amyloid lesions and cognitive impairment by altering the microbiome-gut-brain signaling axis

There is growing evidence that intermittent fasting has multiple beneficial effects on human health, including cancer, cardiovascular disease, metabolic disease, and neurological disorders
.
In this latest study, the research team found that intermittent fasting showed strong protective effects
in the Alzheimer's disease mouse model 5XFAD by reducing Alzheimer's disease-like lesions.
This protective effect is related
to the gut-microbiome-metabolite-brain signaling axis.
Importantly, the study demonstrated that metabolites enriched by intermittent fasting, specifically sar and dimethylglycine (DMG), mimic the protective effects
of intermittent fasting.

Overall, these findings suggest that intermittent fasting regimens are a potential way to prevent Alzheimer's disease progression, acting through the gut-microbiome-metabolite-brain signaling axis as an innovative Alzheimer's disease treatment
.

Original source:

Pan， RY.
， Zhang， J.
， Wang， J.
et al.
Intermittent fasting protects against Alzheimer’s disease in mice by altering metabolism through remodeling of the gut microbiota.
Nat Aging 2， 1024–1039 (2022).
https：//doi.
org/10.
1038/s43587-022-00311-y