Identification of Signaling Pathways That Mediate Dietary Restriction-Induced Longevity in Caenorhabditis elegans

Abstract

Aging is a complex process of accumulation of molecular, cellular, and organ damage leading to loss of function and increased vulnerability to disease and death. Despite the complexity of aging, progress has been made in not only understanding molecular mechanisms that regulate aging but also devising interventions which extend lifespan. Recent work has shown that a reduction in food intake without causing malnutrition, dietary restriction (DR), can increase the healthy lifespan of laboratory model organisms, including yeasts, flies, worms, fish, rodents, and rhesus monkeys. DR has also been shown to protect rodents and rhesus monkeys from age-related disorders, and it reduces risk factors for diabetes, cardiovascular disease, and cancers in humans [1, 2]. In mammals, two types of DR regimens, chronic calorie restriction (CR) and intermittent fasting (IF), have proven effective in increasing lifespan and disease resistance [3, 4]. In CR, there is actually a net decrease in calorie intake. In contrast, IF, in which animals are subjected to fasting intermittently, can extend lifespan without a net decrease in total calorie intake. However, an IF regimen has not been established in invertebrate model organisms. Moreover, because it seemed that both CR and IF regimens extend lifespan through a common mechanism, the two regimens have not been strictly distinguished.