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February 4, 2012: by admin
It’s Not Sirtuin1, it’s cAMP-dependent phosphodiesterases
While researchers have argued over whether Sirtuin1 is the direct or indirectly-activated gene responsible for its molecular mimicry of calorie restriction, researchers now claim resveratrol works directly by inhibiting enzymes called cAMP-dependent phosphodiesterases which then triggers a cascade of events that includes Sirtuin1. You also see the name of a pharmaceutical company in Japan participating here. (see attached paper)
Cell 148, February 3, 2012
Ruth I. Tennen,1,2 Eriko Michishita-Kioi,3 and Katrin F. Chua1,2,*
1Department of Medicine, Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA 94305, USA
2Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA
3R&D Division, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
*Correspondence: kfchua@stanford.eduDOI 10.1016/j.cell.2012.01.032
Despite resveratrol’s well-documented health benefits, its mechanism of action remains controversial.
In particular, the direct molecular target of resveratrol has been elusive. Park et al. now show that resveratrol directly inhibits cAMP-dependent phosphodiesterases, triggering a cascade of events that converge on the important energy-sensing metabolic regulators AMPK, SIRT1, and PGC-1a.
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