2023 Alzheimer's Association Research Grant (AARG)

The Role of Prolonged Fasting in the Effects of Calorie Restriction on AD

How might fasting promote healthy aging and protect against the risk of Alzheimer’s?

Dudley Lamming, Ph.D.
University of Wisconsin-Madison
Madison, WI - United States

Background

Growing evidence has shown that individuals who consume low-calorie diets have a reduced risk for developing Alzheimer's and other disorders of aging. In recent studies, low-calorie diets were found to extend lifespans and slow or prevent the development of dementia in animal models of Alzheimer’s. 

Low-calorie diets, however, are more  difficult to implement in human populations. To overcome this, many researchers are working on understanding the biological mechanisms by which low-calorie diets promote healthy aging. A goal of this research is to develop drugs that enable people to benefit from the effects of reduced calorie diets without having to undertake the diets. These drugs are called calorie restriction mimetics. 

Using cognitively unimpaired mice, Dr. Lamming and colleagues have shown that a prolonged daily fast (a period of not eating) is necessary for the beneficial effects of a low-calorie diet. They believe that understanding how fasting, calorie restriction, or both contribute to the health benefits of low-calorie diets may help guide translational studies and the development of calorie restriction mimetic drugs.

Research Plan

Dr. Lamming and colleagues will study the contributions of fasting and calorie restriction in both male and female genetically engineered Alzheimer’s-like mice. They will investigate which of the health benefits of a low-calorie diet are attributable to fasting and which are due to reduced calorie intake. 

The researchers will then study the brains of these mice to identify sex-specific and sex-independent biological pathways associated with improvements in Alzheimer’s-related changes in the brain and cognition. The research team will investigate the effects of fasting and calorie restriction on energy production (metabolism) and gene activity in male and female genetically engineered Alzheimer’s-like mice. They will identify biological pathways associated with Alzheimer’s-related brain and behavior changes and compare how these pathways are impacted by sex and diet.

Impact

The findings may shed light on the mechanisms underlying the protective effects of a low-calorie diet. The results of this project may identify biological pathways mediated by fasting as potential therapeutic targets for the treatment and prevention of Alzheimer’s.