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Resveratrol
Longevity
Curr Med Chem. 2008;15(19):1887-98.
Trans-resveratrol: a magical elixir of eternal youth?
Orallo F.
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela (La Coruña), Spain. fforallo@usc.es.
Trans-resveratrol or (E)-resveratrol [3,4',5 trihydroxy-trans-stilbene, t RESV or (E)-RESV] is a natural component of Vitis vinifera L. (Vitaceae), abundant in the skin of grapes (but not in the flesh) and in the leaf epidermis and present in wines (especially red wines). In in vitro, ex vivo and in vivo experiments, t-RESV exhibits a number of biological activities, including anti inflammatory, antioxidant, platelet antiaggregatory and anticarcinogenic properties, and modulation of lipoprotein metabolism. Some of these activities have been implicated in the cardiovascular protective effects attributed to t-RESV and to red wine. Prior to 2002 there had been no previous studies describing the potential effects of t RESV on the lifespan extension. However, in the last 5 years, several researchers have reported that t RESV is a potent activator of sirtuin enzymatic activity, mimics the beneficial effects of caloric restriction (CR), retards the aging process and increases longevity in a number of organisms from different phyla such as yeasts, worms, flies and short-lived fish. In addition, t-RESV seems to be effective in delaying the onset of a variety of age-related diseases in mammals (e.g.: rodents). Therefore, this review will basically focus on the possible role of t-RESV to extend life duration and on some of the mechanisms by which t-RESV may act as an anti-aging agent.
SIRT1 confers protection against UVB- and H(2)O(2)-induced cell death via modulation of p53 and JNK in cultured skin keratinocytes.
Cao C, Lu S, Kivlin R, Wallin B, Card E, Bagdasarian A, Tamakloe T, Wang WJ, Song X, Chu WM, Kouttab N, Xu A, Wan Y. J Cell Mol Med. 2008 Aug 4.
Department of Biology, Providence College, Providence, RI 02918, USA.
SIRT1 is a member of a highly conserved gene family (sirtuins) encoding NAD(+)-dependent deacetylases, originally found to deacetylate histones leading to increased DNA stability and prolonged survival in yeast and higher organisms, including mammals. SIRT1 has been found to function as a deacetylase for numerous protein targets involved in various cellular pathways, including stress responses, apoptosis, and axonal degeneration. However, the role of SIRT1 in UV signaling pathways remains unknown. Using cell culture and Western blot analysis in this study we found that SIRT1 is expressed in cultured human skin keratinocytes. Both UV radiation and H(2)O(2), two major inducers of skin cell damage, down-regulate SIRT1 in a time and dose dependent manner. We observed that reactive oxygen species-mediated JNK activation is involved in this SIRT1 down-regulation. SIRT1 activator, resveratrol which has been considered as an important antioxidant, protects against UV- and H(2)O(2)-induced cell death, while SIRT inhibitors such as sirtinol and nicotinamide enhance cell death. Activation of SIRT1 negatively regulates UV- and H(2)O(2)-induced p53 acetylation, since nicotinamide and sirtinol as well as SIRT1 siRNA enhance UV- and H(2)O(2)-induced p53 acetylation, while SIRT1 activator resveratrol inhibits it. We also found that SIRT1 is involved in UV-induced AMP-activated protein kinase (AMPK) and downstream Acetyl-CoA Carboxylase (ACC), phosphofructose kinase-2 (PFK-2) phosphorylation. Collectively, our data provide new insights into understanding of the molecular mechanisms of UV-induced skin aging, suggesting that SIRT1 activators such as resveratrol could serve as new anti-skin aging agents.
SIRT1/PGC-1: a neuroprotective axis?
Rasouri S, Lagouge M, Auwerx J. Med Sci (Paris). 2007 Oct;23(10):840-4.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/Inserm/ULP, 1, rue Laurent Fries, 67404 Illkirch, France.
Neurodegenerative diseases are more and more prevalent in our aging societies. A rapid overview of the etiology of many neurodegenerative diseases like Alzheimer, Parkinson, Huntington disease and amyotrophic lateral sclerosis suggests a tight link with mitochondrial dysfunction. Since it has been recently demonstrated that activation of the SIRT1/PGC-1 pathway, in a metabolic context promotes mitochondrial function, we performed a detailed literature review on the implication of this pathway in neurodegeneration.
Interestingly, transgenic mice with impaired PGC-1 expression have neurodegenerative lesions and show behavioural abnormalities. As evidenced from independent investigations, enhanced SIRT1 activity has been demonstrated to protect against axonal degeneration and to decrease the accumulation of amyloid beta peptides, the hallmark of Alzheimer disease, in cultured murine embryonic neurons. In addition, several studies suggest that resveratrol, a specific activator of SIRT1, could have protective effects in animal models of neurodegenerative diseases. Taken together, these results strongly suggest that the modulation of the SIRT1/PGC-1 pathway, which has not been well documented in the central nervous system, could become the cornerstone for new therapeutical approaches to combat neurodegeneration.
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