| What's with all the hype about esveratrol? It's all | | | | were unchanged compared to wild mice, which |
| about longevity. Not the fountain of youth, | | | | showed a large increase in activity nine months |
| perhaps, but some scientists, and major | | | | after caloric restriction. However, these mice |
| pharmaceutical companies are betting it's a genie | | | | were smaller and did not lose a high percentage |
| in a bottle. Or maybe a pill. And with the news | | | | of their body weight. |
| media pouncing all over this recently, touting hot | | | | Pani and colleagues suggest their leaner smaller |
| and snazzy, "hey drink a glass of wine and live | | | | sizes contributed to Chen's endpoint. Gene |
| longer" headlines, it is spurring momentum as only | | | | expression profiling in mice studies showed that |
| it could in America. | | | | alterations in chromatin structure and transcription |
| Simply, scientists are theorizing, experimenting and | | | | were somewhat modified at lower dosages |
| hedging on resveratrol's ability to lessen the aging | | | | (Barger, 2008) but further research into those |
| process. There are thousands of studies and | | | | pathways are needed. Barger found that |
| patents being published and granted on | | | | resveratrol and caloric restriction do not affect |
| resveratrol, and blog postings are sky high. In a | | | | SIRT1 in mice for heart, liver, skeletal, and brain |
| mass-media, quick-fix society, it is easy to | | | | tissue because they did not up-regulate any |
| understand why one would want to have a few | | | | mRNA or protein for SIRT1. Therefore, there |
| glasses of vino or buy some product off the | | | | may be another mechanism of action, pathway, |
| Internet to decelerate the aging process. | | | | or gene responsible for this in murine tissues. |
| Resveratrol (3,5,4'-trihydroxystilbene; CAS# | | | | GSK Gambles on Sirtris |
| 501-36-0) is found in nature. It has yet to be | | | | Scientific unknowns aside, GlaxoSmithKline paid |
| proven to combat any type of illness or disorder, | | | | $720 million in June 2008 for Sirtris, a startup |
| and its pathways, interactions, and mechanisms of | | | | founded in 2004. Sirtris' main focus is resveratrol |
| action are mostly unknown. It could be that some | | | | mimetics to induce caloric restriction and ultimately |
| other compounds in certain red wines are actually | | | | switch the body into tissue survival mode, which |
| contributing to the effects attributed to | | | | ultimately extends tissue lifespan. A New York |
| resveratrol. | | | | Times article quotes Dr. Leonard Guarente of |
| How It Works | | | | Sirtris as saying that Barger's study did not |
| Here's the nerdy science part (you non-scientists | | | | measure activation of sirtuin, just the amount, |
| can skip this). Resveratrol activates Sirt1 in | | | | suggesting another point of view on the action of |
| humans and Sirt2 in yeast. Sirtuin's protein product | | | | resveratrol on both caloric restriction and sirtuin. |
| pathways are not fully understood, but they are | | | | The idea of increasing life spans via caloric |
| postulated to modulate metabolism and | | | | restriction is quite solid as a plausible mechanism |
| inflammation, and regulate the aging process. The | | | | for drug development. The National Institute on |
| S. cerevisiae family members and human five | | | | Aging (NIA) is funding the Comprehensive |
| member class of genes act via their | | | | Assessment of Long-Term Effects of Reducing |
| NAD(+)-dependent histone deacetylase activity, | | | | Intake of Energy (CALERIE) clinical trial to |
| which can ultimately affect age-related processes | | | | determine the effects of a 25 percent caloric |
| such as tumorigenisis, cardioprotection, or | | | | reduction in 250 healthy and normal weight men |
| mortality extension over the long term by | | | | (ages 20-50) and women (ages 20-47) for two |
| regulating epigenetic gene silencing, suppression of | | | | years to protect against age-related disease |
| rDNA recombination, or altering chromosomal | | | | processes. The principal investigator is Dr. James |
| remodeling/transcription. As an example, this | | | | Rochon from Duke University, and the study is |
| means resveratrol might make you live longer by | | | | expected to publish its results in 2010. Early |
| keeping tumors at bay or by protecting your | | | | indications found in this study include a reduction in |
| heart. | | | | both fasting insulin levels and core body |
| What is really going on is that scientists | | | | temperatures, both which are correlated to |
| understand that humans cannot keep on a diet | | | | longevity. |
| that restricts calorie intake as an anti-aging regime. | | | | Preclinical Studies Under Way |
| So, R&D efforts are well under way to | | | | The current pharmaceutical pipeline, according to |
| substitute dietary resveratrol for self-discipline, | | | | Adis R&D Insight, shows only preclinical |
| allowing people to use resveratrol to induce caloric | | | | status in the United States for sirtuin as a |
| restriction without having to eat less food. The | | | | mechanism of activation. The development of |
| reduction of calories, in turn, is hypothesized to | | | | more stable molecules could lessen the amount of |
| mimic longevity at a cellular level. | | | | dosing needed to elicit a clinically effective |
| Studies in Mice | | | | response; even if there are differing opinions on |
| Some studies are showing an extended lifespan in | | | | what is a clinically effective dose. These |
| invertebrates (S. Cerevisiae, C. elegans, Drosophila, | | | | companies are on their way in the race of the |
| for example) and decreased mortality in mice that | | | | "first to market."Since most of these studies are |
| are given high doses of resveratrol, which mimics | | | | in vitro or should I call them "in vino" studies more |
| caloric restriction. Chen and colleagues (2005) | | | | mammalian studies and clinical trials done should |
| studied knockout mice for Sirt1 and found that | | | | continue to tip us in the right direction. |
| caloric restriction and increased physical activities | | | | |