Embodiments herein relate to agents that mimic calorie restriction (CR) to extend life span, especially agents that lower the level of cytosolic NADH and increase the level of cytosolic NAD+ (relative to NADH) required to mimic calorie restriction that results in life span extension, at least in part by inhibition by NADH of SIR2, which is a key regulator of life span in both yeast and animals. NADH is a competitive inhibitor of SIR2, an NAD-requiring NAD-dependent histone deacetylase required for chromatin silencing and life-span extension. An overall reduction in NADH activates SIR2 and extends life span. The use of fluorescence measurements of NADH levels in a 96-well plate assay utilizing Bakers yeast (Saccharomyces cerevisiae) as a model to screen for agents and supplements that lower NADH levels is disclosed herein. A caloric restriction mimetic contains 1 part Mg2+ malate, 1 part turmeric and 98 parts dehydrated potato skins.
