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Sirtuins as potential targets for metabolic syndrome

Nature volume 444, pages 868–874 (2006)Cite this article

Abstract

Metabolic syndrome threatens health gains made during the past century. Physiological processes degraded by this syndrome are often oppositely affected by calorie restriction, which extends lifespan and prevents disease in rodents. Recent research in the field of ageing has begun to identify important mediators of calorie restriction, offering the hope of new drugs to improve healthspan. Moreover, if metabolic syndrome and calorie restriction are opposite extremes of the same metabolic spectrum, calorie restriction mimetics might provide another therapeutic approach to metabolic syndrome. Sirtuins and other important metabolic pathways that affect calorie restriction may serve as entry points for drugs to treat metabolic syndrome.

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Figure 1: Metabolic syndrome and calorie restriction are balanced at opposite ends of the same spectrum by diet and physical activity.
Figure 2: Pathways of SIR2 activation by moderate calorie restriction in yeast and Drosophila.
Figure 3: Influence of SIRT1 on glucose homeostasis in three mammalian tissue types.
Figure 4: Functions of SIRT3 and SIRT4 in regulating the entry of acetate or amino acids into central metabolism.
Figure 5: Model of the effects of SIRT3, SIRT4 and SIRT7 in different tissues during calorie restriction.

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Acknowledgements

The author apologizes for the many studies and references that could not be included because of space limitations. Work from the author's laboratory was supported by the NIH.

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  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Leonard Guarente

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Leonard Guarente is a founder of Elixir Pharmaceuticals.

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Guarente, L. Sirtuins as potential targets for metabolic syndrome. Nature 444, 868–874 (2006). https://doi.org/10.1038/nature05486

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