Mammalian Sirtuins, Cellular Energy Regulation, and Metabolism, and Carcinogenesis

The sirtuin gene family (. SIRT) has long been hypothesized to regulate the aging process via the regulation of energy metabolism, as well as playing a role in cellular repair. In this regard, it is proposed that one function of sirtuins is to monitor cellular energy and/or metabolic requirements and availability and to direct acetylation signaling to ensure that energy production matches energy consumption. This connection between sirtuins and metabolism may be the mechanistic link, at least in some significant part, to the physiology of aging. Over the last 8 years, multiple publications have shown a connection between the dysregulation of sirtuin proteins and a role in both carcinogenesis and tumor cell resistance. Thus, since it is a very well-established observation that tumor cells exhibit altered energy and metabolism and the rate of malignancies increases significantly with age, it also seems reasonable to propose that the dysregulation of cellular energy and/or metabolic pathways may provide the mechanistic link between aging, metabolism, and an aging-related tumor-permissive cellular phenotype. As such, in this review we will attempt to connect how changes in sirtuin enzymatic activity in mice, as well as genomic data in human tumors, demonstrate a role for sirtuin dysregulation and carcinogenesis in mice and men.