An open access commentary: "Aging is now viewed as a plastic phenotype that can be altered by nutritional, pharmacological and genetic manipulations. However, most pro-longevity mutations are discovered by systematic gene deletion or RNA interference screens, which mainly reveal abolished or diminished gene functions. In our recent publications, we used global acetylation proteome screens to study aging in yeast, and showed that enhancing the function of certain genes through specific acetylation can promote longevity. ... It is well known that acetylation of histone proteins in cultured human fibroblasts decreases during aging, which is believed to be directly related to decreased metabolic rate and reproductive capacity associated with aging. However, histone deacetylation is not likely to be a universal driving force of aging because histone acetylation and deacetylation mimetics similarly shortened life span, which could simply reflect nonspecific fitness decreases in both instances. Extension of lifespan promoted by certain genetic and/or pharmacological perturbations will more likely lead to identification of bona fide regulatory factors of aging. ... Aging is conventionally thought to be characterized by accumulation of molecular, cellular, and organ damage, leading to increased vulnerability to disease and death. Our data, on the contrary, support the idea that the gradual loss of a crucial component promoting 'healthy young status' might underlie an intrinsic aging process. Many of the mutations that extend life span decrease the activity of external nutrient signaling, such as the IGF (insulin-like growth factor)/insulin and the TOR (target of rapamycin) pathways, suggesting that they may induce a metabolic state similar to that resulting from periods of food shortage."