Resveratrol, a phytonutrient most commonly associated with red wine, might help keep you young. Researchers have recently been investigating its potential to act as a calorie-restriction mimetic to delay some of the detrimental processes associated with aging. Today we’ll be exploring the science to see how resveratrol could play a role in extending the human lifespan.
Calorie restriction (CR) has been extensively studied in a range of species such as yeast, worms, rodents, spiders and fish. It can be defined as a reduction of calorie intake to approximately 30-50% of what one would eat “ad libitum” (Latin for “at one’s pleasure) while still maintaining adequate nutrition. There are different ways to do this; in an experiment, investigators might choose to vary proportions of carbohydrate, fat, or protein. People have been practicing CR for health in one form or another for hundreds of years, but the first real scientific study showing that it lengthens lifespan was done in rodents in 1935. Since then, many other studies have duplicated these results in mice with average increases in lifespan of 20-30%. Animals that have been placed on a calorie-restricted diet are typically smaller, leaner, and more active than those that are allowed to feed ad-libitum. They show improvements in body repair mechanisms such as wound healing, as well as lower rates of cancer and autoimmune disease. Studies looking at short-term CR in humans have found similar physiological results. As the results of calorie restriction in animals have been so promising, investigators are now starting to study long-term CR in non-human primates (i.e. monkeys) to see what it might mean for people.
CR influences body systems in a variety of ways. It is associated with decreased inflammation and decreased reactive oxygen species (ROS) damage to tissues. It has been shown to improve insulin sensitivity and therefore reduce diabetic symptoms in both humans and animals. It can also significantly reduce risk for cardiovascular disease by lowering blood pressure, triglycerides, and cholesterol. One of the most researched mechanisms is its impact on metabolism. Both humans and animals on CR diets have been shown to have lower metabolic rates; they expend less energy to sleep, digest food, and move around. A lower metabolism may sound like a bad thing, since we’re always hearing about ways to eat and exercise to rev up our metabolisms and burn more calories. However, we have to remember that the goal with CR isn’t fat loss (although that’s going to happen anyways with the severe reduction in calories). It’s all about maximizing energy usage to make physiological systems more efficient and prolong survival.
If CR can have so many amazing effects on the body, why aren’t we all doing it? With such high rates of obesity and chronic disease, it seems like the perfect public health intervention. For one, it would be pretty hard to convince most people to cut down their food intake to one third to half of what they’re currently eating. Food is so much more than sustenance for us; it’s a source of pleasure that is interwoven into many aspects of society. We also live in an obesogenic environment in which high-calorie food is available anytime and anywhere.
CR is also associated with adverse health effects, with the primary one being difficulty having children. Laboratory animals often show a reduced ability to produce offspring when their caloric intake is drastically limited. This makes sense evolutionarily; if there isn’t enough food around, the body is going to maximize its own efficiency and delay unnecessary processes such as reproduction until environmental conditions are more favorable. Hunger can also cause irritability, and CR-associated fat loss can make one uncomfortably susceptible to cold. All of this has lead researchers to search for calorie-restriction mimetics: substances that can favorably impact aging processes in the same way that CR does. One such potential substance is resveratrol.
Similarly to CR, resveratrol has been shown to extend the lifespan of simple model organisms such as yeast, flies, and fish. The key seems to be an enzyme called Sirt1, which CR and resveratrol both activate. Activation of Sirt1 results in an improvement in glucose and fat utilization in metabolism. It has also been shown to improve signaling between neurons and therefore support brain health. Apart from its impact on Sirt1, resveratrol has the potential to increase longevity in humans by reducing the risk of chronic diseases such as diabetes, cardiovascular disease, and Alzheimer’s disease. Like CR, resveratrol can improve insulin resistance, reduce inflammation, and counteract oxidative stress. Human data supports these findings; subjects that received short-term resveratrol supplements have demonstrated a range of positive effects from reduced blood pressure and cholesterol to an overall better metabolic profile.
Although the metabolic effects of resveratrol are clear in both humans and animals, resveratrol supplementation has not been proven to extend lifespan in normal body weight mice. Obese mice given resveratrol lived longer, but this raises the question of whether resveratrol can act as a true CR mimetic for the average human or whether it is mostly useful as a tool to fight the problems caused by obesity. Investigations are ongoing to see whether resveratrol can extend the lifespan of non-obese mammals.
Over the past five posts, I’ve examined resveratrol’s impact on a range of human health conditions. It began to get serious media attention in the early 1990’s when researchers suggested that its presence in red wine might make it responsible for the French paradox, which is the observation that although the French typically eat a diet high in saturated fat, they have relatively low levels of heart disease. It has been implicated as a potential treatment for diabetes, cardiovascular disease, Alzheimer’s disease, and now as an anti-aging agent. Although research on the phytonutrient is extensive in rodents, investigators are only just starting to look at it in human clinical trials. They’re proceeding with caution, as we still don’t know how much resveratrol is toxic or what effect it has on the human body when used long-term. However, the health effects that it has been shown to have so far make it a topic of great interest for researchers, doctors, and pharmaceutical companies. Once we figure out how much resveratrol is safe, we may see a big increase in the market for supplements as well as resveratrol-enriched foods and medications.
Although resveratrol is present in many foods such as blueberries, cranberries, and peanuts, we have come to associate it primarily with red wine. Unfortunately for those of us who like to indulge, red wine alone is unlikely to provide enough resveratrol to beneficially impact your health; studies have shown that you would need to drink an average of several hundred glasses of wine at a time to have a clinical effect. However, moderate alcohol consumption (1 drink a day for women and 2 for men) has also been associated with reduced mortality, so I’m not going to kill your buzz just yet. Enjoy your wine in moderation, and know that it’s not the only way to get this multi-talented phytonutrient.
References
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