Molecular Genetics of Dietary Restriction

Dietary Restriction (DR), a moderate reduction in food intake without malnutrition, is the most successful intervention discovered to date for increasing healthy lifespan in multiple species. DR has been shown to prolong median and maximum lifespan in organisms spanning the evolutionary spectrum, from single-celled yeast to non-human primates. Critically, DR also has profound effects on age-related pathology, delaying the onset and severity of many complex diseases including metabolic disease, neurodegenerative disorders, cardiovascular disease and cancer. However, DR also imposes negative physiological, psychological and social side-effects. One aim of our laboratory is to elucidate the molecular mechanisms governing the positive effects of DR on health, separate from those that are detrimental, with the goal of developing novel small molecules that mimic the effects of DR.

By taking advantage of the evolutionary conservation of DR, we can use easily manipulatable organisms such as the nematode worm C. elegans to determine the genetic pathways responsible for the beneficial effects of DR on pathology, and use this knowledge to develop novel, multi-target therapeutics for human disorders.