The I'm Not Dead Yet (INDY) gene is one of the earlier longevity genes discovered by researchers in course of investigating the effects of calorie restriction. Here is a recent update: "It is known that excess calorie consumption leads to obesity, insulin resistance and increased mortality, whereas calorie restriction reduces accumulation of body fat and improves cellular energy balance and insulin action - reversing obesity and type 2 diabetes, delaying the aging process, and prolonging life in primates and many other species. It has also been shown in the past that reduced expression of the so-called 'INDY' gene in D. Melanogaster flies and C. elegans worms promotes longevity in a manner similar to calorie restriction. But until now, the cellular mechanism by which this happens was unknown. [Researchers] generated a mouse with the so-called 'INDY' gene deleted. Loss of the gene altered chemical levels in the cellular signaling network in a way that improved mitochondrial action in the liver, metabolism of fatty acids, and cellular energy transport. Overall, these traits protected the mice from diet-related accumulation of body fat and insulin resistance that evolve, as we age, into type 2 diabetes. Discovering how deletion of the INDY gene would impact mitochondrial metabolism in the liver was key, because that is the main organ where the INDY gene does its work."

Link: http://opac.yale.edu/news/article.aspx?id=8772