Brown Fat, Cold Therapies, and Slowing Down the Aging Process
When he was young, David Sinclair’s grandmother told him everybody and everything will one day die. This sober fact kick-started a fascination with biology—and now, as a professor of genetics at Harvard, Sinclair is advancing our understanding of how we age and how to slow down or even reverse these processes. In his book, Lifespan, Sinclair puts forth the idea that aging is simply a disease that we’re beginning to learn how to treat. We asked him to tell us more about brown fat, resveratrol, and some of his more radical theories.
(For more with Sinclair, listen to his conversation on The goop Podcast.)
A Q&A with David Sinclair, PhD
There are two main types of information in our body’s cells: The first is genetic information, and the second is epigenetic information. Epigenetics are chemical changes that occur on our genome that dictate when genes are turned on and off. We know that the environment—how we’ve lived our lives, if we’ve been fasting or exercising, and so on—slows down or accelerates the ticking of that epigenetic clock.
“Epigenetics are chemical changes that occur on our genome
that dictate when genes are turned on and off.”
My lab discovered that epigenetic information is probably more important for our long-term survival than the actual genome itself, although both are essential. Epigenetic information is lost more quickly than genetic information because genetics are a digital record, whereas epigenetics are an analog. Anybody who has had an analog device, like a record player or a cassette tape, knows that they’re not very good at storing information in the long run. By the time we’re eighty, our cells have lost the ability to read the right genes at the right time. They forget to be the kind of cells that they were when they were young, and that’s how we get diseases. We call this aging. Unfortunately, over the last couple hundred years, we’ve decided to treat just the symptoms of aging, which are the diseases that kill us, rather than actually tackling aging at the core.
There are three main longevity pathways. The first are sirtuins, which respond to the environment. Then, there’s mTOR, which registers how much protein you’ve been eating. And the third is called AMPK. The activation of any one of these three pillars of longevity will give health benefits that slow down aging.
My lab works with the sirtuin pathway. There are seven genes in a certain family called sirtuins that respond to the environment and protect the epigenome. And we’ve shown that when we activate these sirtuins, either with lifestyle or natural molecules, we get improved health and longevity in old age. Being hungry every once in a while, intermittent fasting, exercising, or losing our breath makes the sirtuin genes more active. The overall theme is that anything that doesn’t kill you makes you live longer. Even as little as fifteen minutes every few days is sufficient to get those activities up and running.
There is also some evidence that being cold or exposing your body to heat also activates those same pathways. Specifically, the sirtuin-3 gene gets activated by cold, which promotes the browning of fat, which we believe is good for us. Brown fat is full of mitochondria that use energy and speed up the metabolism. This is beneficial because it reduces the amount of the fat that we put on and also because browning seems to produce healthy protein signals. It’s been shown that you can make white fat turn brownish or beige by being cold. White fat is very bad, especially around your organs, whereas brown fat under the skin is healthier. The older you get, the harder it is to make brown fat. That’s why I say that it’s good to start early with these lifestyle changes.
There are plenty of ways to be cold. You can wear less clothing. If you live in Boston, you can go out in the cold. You can sleep with fewer bedsheets and burn off energy while you are asleep at night. You can jump in an ice bath. I just go into a cold tub, which is four degrees Celsius, and try to spend a couple of minutes in there, then follow with a sauna to warm up, and cycle through that. When I was researching for my book, I was skeptical, because cryotherapy sounds like a fad. But when I looked into it, the science fit. We know from mice studies that if we manipulate the systems that control body temperature, we can make them live longer.
We have a lot more data about heat than we do about cold, because sauna bathing has been around since Roman times. It’s been associated with dramatic reductions in cardiovascular disease. In one study from Finland, people who spent between four and seven days a week in a sauna had a twofold reduction in fatal cardiovascular events and all-cause mortality. We don’t know exactly how the heat works, but I hypothesize that it’s probably turning on the same defenses that all of these other stressors do. We know that if you turn up the temperature on a yeast cell, it will activate the sirtuins, and they will live longer as a result. The same processes may occur in our bodies, too, at least superficially on the skin.
Some of the sirtuins respond to cold, some respond to diet, and some respond to DNA damage. We try do a variety of things that wake up the sirtuins out of their complacency and get them to work harder. Otherwise, we’re just at the whim of their decay and entropy over time. I don’t think it’s sufficient to do just one of these things. I think the combination is key, which is why I do all of those things.
We’ve discovered some molecules that may make both mice and humans healthy and live longer. One is resveratrol, which I’ve been taking for the past twelve years. It has been shown in clinical trials in humans to improve blood sugar levels and reduce inflammation. Another is NMN, which is an NAD booster. NAD is the fuel for the sirtuin enzymes. In mice, it has been shown to mimic exercise and fasting and from our clinical trials, we think it probably has the same effect in humans, although we need more human evidence to confirm this. The third molecule, Metformin, was developed for type 2 diabetes but is increasingly thought to protect you against cancer, heart disease, and potentially even Alzheimer’s because it turns on the AMPK pathway related to cellular energy homeostasis (one of the three longevity pathways I mentioned above).
“Colored plants and organic foods that have not been kept under perfect conditions are high in resveratrol and other molecules like it. Deep-colored wines have the most resveratrol.”
I also think that our diet of eating three meals a day plus snacks is killing us. In Blue Zones, where people don’t eat three meals a day and are more active, they live longer. And here’s the really interesting thing: They also consume more resveratrol. Resveratrol and a larger family of plant molecules activate the sirtuins. Plants make these molecules when they are stressed out, like when they don’t get enough water, nutrients, or sunlight. I theorize that when we eat plants that have been stressed just before picking, we get the health benefits of these resveratrol-like molecules. The plants are making what I call xenohormetic molecules that increase stress tolerance so that they can survive. And when we eat those stressed plants, our bodies are getting the signal: Whoa, our food supply might run out. Let’s hunker down and go into survival mode. So drinking red wine for most of your life or eating olives that have been stressed out on the hillside gives our bodies signals from the plants that times might be tough in the future so that the body goes into conservation mode, protecting itself against potential adversity. Eating these xenohormetic molecules is what gives the people in the Blue Zones long, healthy lives.
Colored plants and organic foods that have not been kept under perfect conditions are high in resveratrol and other molecules like it. Deep-colored wines have the most resveratrol. Most people think that it’s the antioxidants in these fruits and vegetables that are good for us, but I think that the most important thing is these xenohormetic molecules that the plants are making.
My lab took the resveratrol discovery all the way to human trials and effectively treated psoriasis in the skin. For the past two years, I’ve been running clinical trials on an NAD booster at Harvard. So far, we have safety data to show that NAD boosters are safe in short-term studies, but more on this work will be published in the next year.
Last year, we published results showing that when you give NMN to a mouse, parts of its body get younger. We were able to mimic the benefits of exercise. And we found that the older mice could run up to twice as far. Some of the old mice ran so far that the treadmill stopped working because the software wasn’t written for a mouse to do that. We tracked this finding down to increased energy and increased blood flow. Our hope is that we can use these medicines that we’re developing not just for healthy people to live longer but also to treat diseases where people need more energy or blood flow. It could get people out of wheelchairs. You can also bet there are a lot of athletes who are interested in what I work on.
Last year, my colleagues made a remarkable discovery about reprogramming, and we will be publishing the first scientific paper on this soon. Our discovery is that there’s a backup hard drive of useful information that we can use to reset the age of the cell. We’ve used gene therapy in mice to restore their vision, and we’re hoping to be able to reset other parts of the body and potentially even the entire body. It’s one thing to slow down aging; it’s quite another to be able to repeatedly reverse the age of a tissue. And that’s what makes me very excited about the future. It’s the equivalent of having discovered that you don’t need to fly in a hot air balloon because now we can build airplanes. It’s a totally different approach to this problem, and we’re hoping to start clinical trials on it to treat glaucoma in a couple of years.
David Sinclair, PhD, is a professor of genetics and a codirector of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. His research has advanced our understanding of how we age and how to slow these processes. He is the author of Lifespan and has a website by the same name where he blogs about his research on aging. Find him on twitter @davidasinclair and on Instagram @davidsinclairphd.
This article is for informational purposes only, even if and regardless of whether it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of goop.
