Resveratrol, an antioxidant found in red wine presented since 2003 presented for its potential to lower risk for cardiovascular disease and neurodegeneration by increasing cell survival and slowing aging: 2014 Study – Diet rich in resveratrol offers no health boost
Reporter: Aviva Lev-Ari, PhD, RN
Related to this study are other articles published in this Open Access Online Journal, including:
Novel Cancer Hypothesis Suggests Antioxidants Are Harmful
Reporter: Larry H Bernstein, MD, FCAP
Biology, Physiology and Pathophysiology of Heat Shock Proteins
Curation: Larry H. Bernstein, MD, FCAP
Letters to Nature
Nature 425, 191-196 (11 September 2003) | doi:10.1038/nature01960; Received 13 June 2003; Accepted 31 July 2003; Published online 24 August 2003
Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
See associated Correspondence: Corder et al. , Nature 426, 119 (November 2003)
Konrad T. Howitz1, Kevin J. Bitterman2, Haim Y. Cohen2, Dudley W. Lamming2, Siva Lavu2, Jason G. Wood2, Robert E. Zipkin1, Phuong Chung1, Anne Kisielewski1, Li-Li Zhang1, Brandy Scherer1 & David A. Sinclair2
- BIOMOL Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA
- Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Masachusetts 02115, USA
- In PubMed:
In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeastSaccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD+-dependent protein deacetylases2, 3, 4, 5, 6. Included in this family are SIR-2.1, a Caenorhabditis elegansenzyme that regulates lifespan7, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor8, 9, 10. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators.
Dr. David Sinclair, now a professor of genetics at Harvard Medical School. He and his colleagues discovered in 2003 that resveratrol could increase cell survival and slow aging in yeast (and later in mice) by activating a “longevity” gene known as SIRT1. Since then, we’ve learned that resveratrol can help
- prevent skin cancer in mice;
- protect against high blood pressure, heart failure, and heart disease in mice;
- improve insulin sensitivity, reduce blood sugar, and blunt obesity induced by a high-fat diet in rodents;
- protect nerves and the brain in various lab animals.
But the dose of resveratrol administered in experiments is always much higher than you’d normally consume in a daily diet. “You would need to drink a hundred to a thousand glasses of red wine to equal the doses that improve health in mice,” says Dr. Sinclair, who was named one of this year’s Time magazine 100 Most Influential People for his anti-aging research. He wasn’t surprised about the results in the JAMA Archives study.
Still, the disappointing results don’t mean that resveratrol and other molecules like it won’t help extend the lifespan or protect against the development of aging-related diseases. Dr. Sinclair points out that drug companies have now created thousands of new synthetic molecules, “that are up to a thousand times better than resveratrol. They prevent cardiovascular disease and neurodegeneration. They also extend lifespan in mice.”
The molecules don’t have catchy names yet—with current such as SRT1720 and SRT2104—but they’re showing promising results in mice. Dr. Sinclair is again helping to pioneer much of this research.
Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults
Importance Resveratrol, a polyphenol found in grapes, red wine, chocolate, and certain berries and roots, is considered to have antioxidant, anti-inflammatory, and anticancer effects in humans and is related to longevity in some lower organisms.
Objective To determine whether resveratrol levels achieved with diet are associated with inflammation, cancer, cardiovascular disease, and mortality in humans.
Design Prospective cohort study, the Invecchiare in Chianti (InCHIANTI) Study (“Aging in the Chianti Region”), 1998 to 2009 conducted in 2 villages in the Chianti area in a population-based sample of 783 community-dwelling men and women 65 years or older.
Exposures Twenty-four–hour urinary resveratrol metabolites.
Main Outcomes and Measures Primary outcome measure was all-cause mortality. Secondary outcomes were markers of inflammation (serum C-reactive protein [CRP], interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]) and prevalent and incident cancer and cardiovascular disease.
Results Mean (95% CI) log total urinary resveratrol metabolite concentrations were 7.08 (6.69-7.48) nmol/g of creatinine. During 9 years of follow-up, 268 (34.3%) of the participants died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of participants who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P = .67). Participants in the lowest quartile had a hazards ratio for mortality of 0.80 (95% CI, 0.54-1.17) compared with those in the highest quartile of total urinary resveratrol in a multivariable Cox proportional hazards model that adjusted for potential confounders. Resveratrol levels were not significantly associated with serum CRP, IL-6, IL-1β, TNF, prevalent or incident cardiovascular disease, or cancer.
Conclusions and Relevance In older community-dwelling adults, total urinary resveratrol metabolite concentration was not associated with inflammatory markers, cardiovascular disease, or cancer or predictive of all-cause mortality. Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study.