Alzheimer’s disease is a debilitating neurodegenerative disease that affects millions of individuals and their families worldwide. With no cure in sight, researchers are continually seeking innovative approaches to reduce symptoms and slow the progression of this devastating disease. One new avenue of research is addressing disruption of circadian rhythms, the body’s internal clock that plays a key role in regulating a variety of physiological processes.Recent research published in cell metabolism We revealed the potential of time-restricted nutrition to correct circadian rhythm disturbances in Alzheimer’s disease.
Many people living with Alzheimer’s disease experience disrupted circadian rhythms. These disruptions manifest as altered sleep patterns, increased nocturnal cognitive impairment, and difficulty falling and staying asleep. A new study looked at a new approach to address circadian rhythm disruption in Alzheimer’s disease: time-restricted feeding (TRF). TRF is a type of intermittent fasting that limits the range of meals you eat throughout the day without reducing your overall food intake.
“Our lab is primarily interested in deciphering changes in how genes are expressed in the brain and how these mechanisms contribute to neural dysfunction and neurodegeneration. ” explained the study authors. Paula Desplatassociate professor of neuroscience at the University of California, San Diego.
“Knowing disease pathways precisely allows us to identify new treatments for diseases such as Alzheimer’s disease. A key regulator of gene transcription is the circadian clock. Loss of circadian rhythms is a key driver of neurodegenerative diseases. It is a hallmark of Alzheimer’s disease that more than 80% of patients experience in the form of disrupted sleep patterns and cognitive impairment in the evening (sunset). We wanted to see if we could correct the pathology of the disease.”
In the study, researchers used mice suffering from Alzheimer’s disease-like conditions as experimental subjects. He divided these mice into two groups. One group adhered to a time-restricted feeding (TRF) schedule, and the other group served as a control and had free access to food at any time.
Mice in the TRF group were exposed to a daily 6-h feeding window, followed by a 14-h fasting period. This TRF schedule is designed to align with your natural circadian rhythm and emulate a more typical eating pattern.
Throughout the study, the researchers conducted a variety of behavioral assessments on the mice, including changes in memory, nocturnal hyperactivity, adherence to a regular sleep schedule, and disturbances during sleep. These assessments provided insight into the behavioral effects of TRF.
In addition to behavioral assessments, Desplatz and his colleagues performed molecular analyzes on both groups of mice. They investigated gene expression patterns associated with Alzheimer’s disease and neuroinflammation. Additionally, since amyloid deposits are a well-known hallmark of Alzheimer’s disease, they measured levels of amyloid protein in the brains of the mice.
Mice receiving the TRF regimen showed significant behavioral improvements compared to the control group. They had better memory, less nighttime hyperactivity, kept a more regular sleep schedule, and experienced fewer sleep disturbances. Overall, these behavioral evaluations showed that TRF alleviated behavioral symptoms of Alzheimer’s disease in mice.
At the molecular level, the researchers found significant differences in gene expression patterns between the two groups. Multiple genes associated with Alzheimer’s disease and neuroinflammation were differentially expressed in the TRF group, suggesting that TRF influences the molecular mechanisms underlying the disease. Additionally, the TRF regimen effectively reduced amyloid protein accumulation in the brains of mice.
“The message from our study is that restricting daily feeding time, rather than limiting the amount of food consumed, restores brain transcriptional rhythms in a rodent model of Alzheimer’s disease,” “Both neuropathology and cognitive impairment were significantly improved,” Desplatz said. he told Cypost. “Although this study has not yet been translated to human patients, our study supports future research into the therapeutic potential of time-restricted eating as a potent circadian regulator of Alzheimer’s disease in humans. It confirms the importance and we want to lead the way.”
Researchers have discovered that TRF affects specific genes and proteins associated with Alzheimer’s disease. One key discovery was a protein called Bmi1, which when deficient in mice causes Alzheimer’s disease-like changes in the brain. TRF helped restore Bmi1 levels to normal.
“We conducted this study primarily focused on the control of gene expression in the brain by the circadian clock,” Desplat explained. “While we expected to see a positive impact on neuropathology, we were surprised to see that multiple measures of Alzheimer’s disease improved in response to time-restricted eating. Another interesting finding was that Because Bmi1 is involved in regulating aging-related cellular senescence and DNA damage responses, we identified Bmi1 as a potential mediator of these effects.”
Mouse models of Alzheimer’s disease play a vital role in advancing our understanding of Alzheimer’s disease mechanisms and in preclinical testing of potential treatments. These models provide a controlled environment to investigate genetic and environmental factors that contribute to Alzheimer’s disease. However, there are also inherent limitations due to differences in mouse and human brain physiology.
“The use of mouse models of Alzheimer’s disease has many limitations because they don’t necessarily reproduce what we see in human pathology,” Desplatz says. “Therefore, we are now trying to determine whether the positive effects of time-restricted eating on Alzheimer’s disease pathology can be replicated in humans. We are also trying to determine whether the specific biology that controls these outcomes can be replicated in humans.” We are conducting additional experiments in mice to understand the clinical processes and identify druggable targets for treatment of the disease.
“Our findings, consistent with a growing body of evidence, indicate that Alzheimer’s disease must be treated in a manner that reflects its complex etiology and pathology,” Desplat added. “Time-restricted eating is a lifestyle change that can be easily and quickly incorporated into daily life. This dietary approach complements pharmaceutical interventions and significantly improves the lives of people affected by the disease. It can be an effective method.”
the study, “Circadian regulation through time-restricted feeding rescues brain pathology and improves memory in a mouse model of Alzheimer’s disease” is written by Daniel S. Whitaker, Laila Akhmetova, Daniel Carlin, Haley Romero, David K. Welsh, Christopher S. Colwell, and Paula Desplatz.