DNA repair, insulin signaling and sirtuins: at the crossroads between cancer and aging.
For many years organismal aging and cancer were viewed as separate entities. Recent studies however have suggested that these two seemingly disparate biological processes may in fact share common biochemical pathways. One area of emerging convergence involves the intersection of pathways known to mediate DNA repair with pathways previously implicated in insulin signaling. Recent evidence suggests that the sirtuin family of proteins act as central mediators of this molecular crosstalk. The coordination of DNA repair with overall energy balance may be essential for reducing the risk of developing cancer as well as for determining the rate at which we age. This review will summarize our current knowledge on how the maintenance of genomic integrity and insulin signaling intersect, the potential regulation of sirtuins in this crosstalk, and how this coordinated regulation may have important implication for both tumor-free and overall survival.
Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA. rmostoslavsky@mgh.harvard.edu
Raul
R
Mostoslavsky
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D020137:Base Pair Mismatch; D004249:DNA Damage; D004260:DNA Repair; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008017:Life Expectancy; D009369:Neoplasms / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D037761:Sirtuins / Q000502:physiology*
D007328:Insulin; D017382:Reactive Oxygen Species; D007334:Insulin-Like Growth Factor I; D037761:Sirtuins