I’ve written about aging and longevity twice before this spring and those articles were called Aging should be considered a disease and we should treat it and The hype of boosting your NAD levels for improved health and longevity. A lot of that writing was inspired by David Sinclair, the Harvard Professor who’s made several podcast appearances recently and also published a new book titled Lifespan: Why We Age, and Why We Don't Have To.
I finally managed to finish the book and it really is a captivating description of what’s taken place in the field of longevity research and where we stand today. Contrary to other scientific books it also becomes rather philosophical, as Sinclair together with co-author Matthew LaPlante discuss the potential implications of people living longer and how that might ultimately question the foundation of everything we assume about our life and society.
The key questions that longevity researchers are trying to answer is what happens to our cells when we age, and is there a way to slow down, or perhaps even reverse, that process? Sinclair is known for talking about two molecules that could have anti-aging properties on the cellular level. These are nicotinamide mononucleotide (NMN) and resveratrol.
As mentioned above, I’ve already written about NMN and how it could be used to boost NAD levels, but I haven’t yet written anything on resveratrol. Resveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi.
Chemical structure of trans-resveratrol. Public domain image.
You can find resveratrol in grapes, blueberries, raspberries, mulberries, and peanuts. Because red wine contains noticeable amounts of resveratrol, it’s been suggested as a possible explanation for the French paradox, i.e. improved cardiovascular outcomes despite a high-fat diet in French people.
We know that the risk of getting certain metabolic diseases, including type 2 diabetes and heart disease, increases as we age. It’s also been shown in animal studies that some of these diseases can be prevented by severely restricting calories. Interestingly, researchers have also discovered that resveratrol can mimic calorie restriction in some ways and extend the lifespans of yeast, worms, flies and fish.
Apparently resveratrol works in a variety of ways, but what people seem to be most excited about is how it, by mimicking calorie restriction, affects the activity of enzymes called sirtuins. Sirtuins control several biological pathways and are known to be involved in the aging process.
In 2013 a study was published in Science showing that resveratrol stimulates production of the sirtuin SIRT1, which blocks diseases by speeding up the cell's energy production centers known as mitochondria. Sinclair, who was part of the study, said that “Now that we know the exact location on SIRT1 where and how resveratrol works, we can engineer even better molecules that more precisely and effectively trigger the effects of resveratrol”.
Resveratrol is only one of many natural and synthetic sirtuin-activating compounds (STACs) now known. And as previously mentioned, similar sirtuin-activating effects can also be achieved by calorie restriction.
What seems clear is that there are still mixed feelings about resveratrol in the scientific community. Some positive articles say that “Resveratrol has [indeed] been shown to mimic effects of caloric restriction, exert anti-inflammatory and anti-oxidative effects, and affect the initiation and progression of many diseases through several mechanisms”. But the Wikipedia page on resveratrol bluntly states that: “Although commonly used as a dietary supplement and studied in laboratory models of human diseases, there is no high-quality evidence that resveratrol improves lifespan or has an effect on any human disease.”
So what to believe? Perhaps best to wait for more research results and meanwhile stick to the original thing, i.e. calorie restriction. That can be done for example through intermittent fasting, which I think is a fairly easy way to implement calorie restriction while living a “normal” life.
But why even go through the hassle of calorie restriction? Well, that’s the one thing where we seem to have consensus among scientists, i.e. it really appears to have effects that can increase our lifespan.