A Conversation With a Harvard Geneticist on How to Live (Well) Past 100 – InsideHook

In Parks and Rec, Rob Lowes Chris Traeger is a perennially positive, supplement-popping 45-year-old who glides through the rooms of Pawnee City Hall with golden retriever energy. He brings vegetable loaves to birthday parties, regularly runs 10 miles during his lunch breaks and touts just 2.8% body fat. In Season 2 of the show, Traeger reveals his lifes goal: to live to 150.

Scientists believe that the first human being to live to a 150 years has already been born I believe I am that human being. At first, it sounds like just another quotable line from a show thats famous for them. Traeger isnt to be taken seriously, after all. One of his other signature adages is simply Stop pooping. (On the exceedingly rare occasions that Traegers body fails him, he lands in a dark place.)

Believe it or not, though, Traegers right. At least one scientist has been predicting humankinds potential to live to 150 for the better part of a decade, a man whos furthered the notion of aging as disease since he arrived at MIT in the late 1990s. That would be Australian Dr. David Sinclair, a biology rockstar and former Time 100 honoree with an Order of Australia (Down Unders version of knighthood), and his own genetics lab at Harvard Medical School.

In September of last year, Dr. Sinclair released Lifespan: Why We Age and Why We Dont Have To. Its an explosive call to arms detailing Dr. Sinclairs core belief, which hes spent decades researching: most humans leave decades of high-quality life on the table simply because society doesnt afford aging the same attention and dollars it reserves for other health crises like cancer and heart disease. The book is one part memoir (Dr. Sinclair recalls the drawn-out final decades of his mother and grandmothers lives), one part crash-course in epigenetics (we hold far more in common with yeast cells than the common person knows) and one part sneak peek into the advancements being made in the worlds preeminent genetics labs (Dr. Sinclairs team has successfully cured blindness in mice).

Most refreshingly, though, Lifespan delights in giving answers. On top of the many science-fiction-esque wonders on display at Harvard Medical School each week (Dr. Sinclair is a pioneer of a practice called cellular programming, which effectively means resetting cells back to a younger age), the book includes functional day-to-day advice on how the layman or woman can activate survival processes in their epigenome, engaging specific sirtuin proteins (a class of protein that helps regulate cellular aging) to help foster greater longevity.

Basically, Sinclairs hypothesis is that eating a certain way, working out a certain way and exposure to a certain kind of temperature can make living past 100 a relative breeze. We recently caught up with Dr. Sinclair to discuss his book, intermittent fasting, Benjamin Button and more.

InsideHook: This book definitely doesnt mince concepts or words. Why was it important to you to write so boldly on aging as a disease?

Dr. David A. Sinclair: The world is in a stupor when it comes to aging. Theres a blind spot. I wrote the book to shake things up, and hopefully wake up those who dont think aging is important or worth working on. We focus as a society far too much on the end consequence of aging, playing whack-a-mole with these diseases that kill us. We ignore whats actually driving these diseases. The more we study aging, though, the more we realize that the diseases we treat are all manifestations of an underlying process. And its treatable.

Some of your peers in the field have said it isnt a good look to be so declarative in your predictions on aging. Have they changed their tune since the book was released?

I havent had any criticism from colleagues since the book came out. Either they havent read it, or theyre okay with my arguments. But also, the world is changing. What used to be considered crazy 10 years ago is no longer crazy. For example, scientists didnt used to say the phrase reversal of aging. But now, its a fact thats doable. Our field has proven that many aspects of aging are reversible, including blindness. Its also partly that I was ahead of the curve, and that things which were once forbidden are now in the realm of discussion and debate.

Im fascinated by the cellular reprogramming work your lab has done. In the book, you invoke F. Scott Fitzgeralds Benjamin Button story to describe how a 50-year-old could soon begin a routine that will have him/her feeling and looking 30 again. Are we actually close to seeing that sort of treatment in the developed world?

The first thing to say is we now understand that changes in your lifestyle can dramatically improve your age and physiology. We used to think that aging was just something that was in our genes, something that we couldnt modify. But very rapidly, within months of changing diet and exercise, you can reverse many aspects of aging. Its never too late, unless youre on your last legs. The fact that its that easy to slow down and reverse aspects of aging just with lifestyle changes totally fits with our understanding of molecular mechanisms. We should be able to slow aging even better with the reprogramming of cells. I see the work weve done as a proof of concept. While its true that Im working hard towards restoring eyesight in people whove lost their vision, its really just the beginning. This work is proof that its possible to restore the age of a complex tissue. In the same way that the Wright brothers werent building rockets to the moon, they could at least imagine that one day it would be possible. Weve shown that there is a backup copy of a youthful epigenome that we can turn on to reset the cell and get it to work again. If thats doable in the eye, it would be rather pessimistic to say we were just lucky to choose the right body part for this to work.

High-intensity training is one of the practices you cite as vital to this process. What about it encourages longevity genes?

Weve found that high-intensity training will induce the sirtuin defenses in the body, similar to what intermittent fasting does. When those genes come on, they defend the cell against diseases, and aging itself. When we dont engage those sirtuin genes, we dont reap the benefits. High-intensity training is particularly good at turning on the sirtuins, because it encourages a hypoxic response, which weve shown leads to the activation of these defense mechanisms. While walking is good, its not as good as doing high-intensity training.

Im glad you mentioned intermittent fasting, another practice you endorse. Are there any mistruths or misunderstandings in the way that popular media portrays it?

Based on recent results in animal studies, its not so much what you eat but when you eat. Of course, you cant eat a hamburger morning, noon and night, then fast the next day and expect to get the maximum benefits. That said, it seems to be more about just having a period of fasting in general. Theres one misconception that people need an optimal mix of protein, carbohydrates and fat, and that thats the most important thing to get right. Id say worry about that less, as long as youre getting nutrients and xenohormetic molecules, which are molecules produced by plants when theyre under stress. As long as youre doing those things, its far more important to skip meals.

One other thing: people claim that there is an optimal intermittent fasting protocol. The truth is, we dont know what the optimal is. Were still learning, and its individual. There are individual differences in all of us. There is a subset of people, myself included, who start producing glucose out of their livers early in the morning, at around 6 a.m. Which means, for me, to start eating breakfast around 7 a.m. makes no sense. Some people, though, have such low blood sugar in the morning that they can barely function. We also dont know the best method. Is it the 16/8 [hours, first on and then off of the fast]? Two days fasting out of every five? We really dont know yet. But we do know that if youre never hungry, if youre eating three meals a day and snacking in between, thats the worst thing you can do. It switches off your bodys defenses. Some fasting is better than none.

Do you eat meat?

I do, but its a gradient. Its mostly plants, then fish, rarely chicken, and almost never red meat.

From an aging perspective, do you recommend that people give up meat?

For the average person, focus on plants. Meat isnt going to kill you if you eat it once in a while, but the reason for the plant-based diet is we know where the hot spots are for longevity. We know what theyre eating. Its not a mystery. Theyre not carnivores. Theyre eating mostly plants, and a little bit of meat maybe, a bit of fish. Theyre consuming olive oil, avocados, red wine and other plants that have xenohormetic molecules. I dont think that thats a coincidence.

Theres been some coverage recently about the rise of wild swimming. In the UK, especially, people have started jumping into freezing cold water and claiming all sorts of health benefits. It reminded me of your points in the book about challenging the thermoneutral zone. Does one need to frequently experience extremely cold temperatures to reap benefits?

Cold baths, cryotherapy I was skeptical. I started out skeptical until proven otherwise. But theres some evidence that making brown fat is good. Adult humans can make brown fat as long as theyre not super old, and cold is a good way to do that. One of my favorite genes, the third of the seven sirtuin genes, boosts brown fat. All of these things that were talking about exercise, fasting, cold therapy, even a sauna its best to mix it up. You dont want to be constantly exercising, constantly hungry, or constantly at one temperature or another. You want to shock the body. Putting a few days of recovery in between makes a lot of sense. As for exposing yourself to cold, a little is still better than nothing. I do it once a week. But Im still trying to figure out when to do these ice baths. There was a study that an ice bath after a workout potentially lowers the benefit of the workout.

Lifespan devotes a ton of pages to metformin, the anti-diabetic medication thats been discovered to activate longevity genes. Are there adverse side effects from taking metformin? It seems a little too good to be true.

As far as drugs go, metformin is very safe. The World Health Organization declared it one of the essential medicines for humanity. One in 10,000 people have an adverse side reaction and have to stop taking it. The majority of complaints are attributed to a queasy stomach feeling until you get used to it. I actually dont mind, because it stops me from getting hungry. [Editors note: Dr. Sinclair takes metformin daily.] It doesnt give you anything like a greater risk of cancer or heart disease. The data actually suggests the opposite. The risk of getting old is pretty high, but the risk of taking metformin is pretty low, based on millions of people taking it.

Youre on the record saying the first person to live to 150 has been born. Would that person need to combine every single practice and innovation that you outline in this book in order to do so?

An important point of clarification: I dont think we have any technology today that would get us to 150. But if youre born today, you can be around until the mid-22nd century. Theres a lot thats going to happen between now and then. Were on a path of technological development. Once you see the trajectory and barriers are broken down, it gives me the license to say someone born today will live far longer than we can imagine. People born today will benefit from technologies that come about after were dead. The big breakthrough is being able to reprogram the body. If we can get that to work, wed be literally able to turn the clock back on cells. Weve done it once we managed to restore vision in mice but you might be able to reset cells twice. Or 100 times. Well just have to see.

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A Conversation With a Harvard Geneticist on How to Live (Well) Past 100 - InsideHook