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Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis
Lindsay E Wu1, Ana P Gomes2, David A Sinclair3
1Laboratory for Ageing Research, Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Abstract:
Why does cancer risk increase as we age? Frequently attributed to the multi-hit hypothesis and the time required to accumulate genomic mutations, this question is a matter of ongoing debate. Here, we propose that the normal decline in oxidative metabolism during aging constitutes an early and important "hit" that drives tumorigenesis. Central to these metabolic changes are the sirtuins, a family of NAD(+)-dependent deacylases that have evolved as coordinators of physiological responses to nutrient intake and energetic demand. Thus, the modulation of sirtuins might be a fruitful approach to reversing the age-related metabolic changes that could underlie tumorigenesis.
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