Archana Unnikrishnan, PhD

Role of DNA methylation in Dietary Restriction mediated insulin sensitivity

Dietary restriction has been shown to increase lifespan and delay the onset and progression of most age-related diseases. One consistent observation in mammals is that dietary restriction has a dramatic effect on insulin sensitivity, which plays a role in dietary restriction’s life-extending action.

One important aspect of dietary restriction is that it can have early effects that create a cellular memory, which persists throughout life. For example, studies have shown that dietary restriction implemented only early in life can increase the lifespan of rodents fed at will for the rest of their lives. It has also been found that insulin sensitivity improves within a month after the implementation of dietary restriction, and persists after dietary restriction is discontinued.

Data from several sources indicate that DNA methylation—a mechanism by which the transcriptional capability of cells can be altered for the life of an organism—might be an important part of dietary restriction’sinfluence on age-related processes. Recent studies also suggest that alterations in DNA methylation are involved in insulin resistance.

Dr. Unnikrishnan hypothesizes that dietary restriction induces metabolic memory by bringing about changes in DNA methylation at specific genomic regions that regulate the expression of genes involved in insulin sensitivity. To test this hypothesis, she will explore the epigenomic changes induced by dietary restriction that persist after reversion to an at-will diet. This is the first study to investigate the possible role of DNA methylation in the metabolic memory of dietary restriction.