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Anti-aging molecule, Sirt1: a novel therapeutic target for diabetic nephropathy

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Abstract

Caloric restriction prolongs the lifespan of many species. Therefore, investigators have researched the usefulness of caloric restriction for healthy lifespan extension. Sirt1, an NAD+-dependent deacetylase, was identified as a molecule necessary for caloric restriction-related anti-aging strategies. Sirt1 functions as an intracellular energy sensor to detect the concentration of NAD+, and controls in vivo metabolic changes under caloric restriction and starvation through its deacetylase activity to many targets including histones, nuclear transcriptional factors, and enzymes. During the past decade, investigators have reported the relationship between disturbance of Sirt1 activation and the onset of aging- and obesity-associated diseases such as diabetes, cardiovascular disease and neurodegenerative disorders. Consequently, a calorie restriction-mimetic action of Sirt1 is now expected as a new therapy for these diseases. In addition, recent studies have gradually clarified the role of Sirt1 in the onset of kidney disease. Its activation may also become a new target of treatment in the patients with chronic kidney disease including diabetic nephropathy. In this article, we would like to review the role of Sirt1 in the onset of kidney disease based on previous studies, and discuss its possibility as the target of treatment in diabetic nephropathy.

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Acknowledgments

JSPS KAKENHI (00452235 to S.K.), the Uehara Memorial Foundation (to S.K.), Takeda Science Foundation (to S.K.) and Banyu Life Science Foundation International (to S.K.), The 4th Annual Research Award Grant of Japanese Society of Anti-Aging Medicine (to D.K.), Grant for Collaborative Research from Kanazawa Medical University (C2011-4, C2012-1) and Grant for Specially Promoted Research from Kanazawa Medical University (SR2012-06).

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All the authors declare no conflict of interests regarding this manuscript.

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Authors and Affiliations

  1. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan

    Shinji Kume & Hiroshi Maegawa

  2. Division of Diabetes & Endocrinology, Kanazawa Medical University, Uchinada-Cho, Kahoku-Gun, Ishikawa, 920-0293, Japan

    Munehiro Kitada, Keizo Kanasaki & Daisuke Koya

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  1. Shinji Kume
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  2. Munehiro Kitada
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  4. Hiroshi Maegawa
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  5. Daisuke Koya
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Correspondence to Daisuke Koya.

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Kume, S., Kitada, M., Kanasaki, K. et al. Anti-aging molecule, Sirt1: a novel therapeutic target for diabetic nephropathy. Arch. Pharm. Res. 36, 230–236 (2013). https://doi.org/10.1007/s12272-013-0019-4

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