SIRT1: Tumor promoter or tumor suppressor?

Over the past decade, an intensive research on the basic biology of aging has identified individual genes either directly or indirectly involved in regulating the aging process in various model. organisms. This allows us to garner all the information available from studies of model. organisms and to apply them to better understand aging and cancer in human. Among many genes thus far reported contributing to aging process, the yeast silent information regutator-2 (SIR2) and its homologues in other species, which belong to the family of type III histone and protein deacetytases, have been the subject of active discussion. The demonstrated roles of SIRT1, the mammalian counterpart of the yeast SIR2, reveal that SIRT1 regulates important cellular processes including anti-apoptosis, neuronal protection, cellular senescence, aging and longevity. Based on the observations that SIRT1 is upregulated in tumor cells, the hypothesis is that deregulation of SIRT1 expression may promote tumorigenesis by altering cellular signaling or by inducing modulation of chromatin remodeling leading to promotion of tumorigenesis. Further studies will shed new tight on the underlying mechanisms of tumorigenesis mediated by SIRT1. (c) 2006 Elsevier Ltd. All rights reserved.