Over the next few decades our accepted notions of what it means to age, grow old and die are going to radically change with massive technological progress. At least, if David Sinclair, PhD has anything to say about it. He’s the author of the New York Times bestseller, Lifespan: Why We Age and Why We Don’t Have To, a new book that explains that the ill health of old age is not something we should accept as inevitable.
As a world-renowned expert on the subject, David Sinclair is qualified to make such statements about aging. He’s a professor of genetics at Harvard Medical School, and a well known online personality and authority on the subject of aging. A painful descent into old age isn’t something we have to accept. David Sinclair explains why in this interview:
You have revealed an exciting new theory, called the Information Theory of Aging. Can you explain this to our readers in simple terms?
The new idea is that we have two major types of information stored in the body: One is digital, one is analog. The digital information is our genome, which surprisingly lasts way longer than 80 years (that’s a new discovery), but it’s the analog information that I find is the problem. The analog information is the epigenome, the structures within the cell that allow some genes to be read while keeping others silent. Because the analog information is very hard to preserve, that’s the first one to fail. And that’s what I believe causes aging.
Can people address this “loss of information” with simple interventions like diet and lifestyle modifications?
The most important thing is to eat less often. That’s not malnutrition; it’s not starvation. I don’t want any teenagers to use this as a reason to not eat enough, but most adults eat too much and they eat too often. And based on some recent results in mice, and also in humans, it looks like it’s just as important when you eat, as what you eat, and perhaps even more important. I’m suggesting that three square meals a day is not optimal for longevity. There are various varieties of fasting that you can do, which I think are potentially helpful. We don’t know which one’s best, but I don’t eat breakfast, except for maybe a few bites of yogurt, and then I don’t eat until late afternoon, sometimes all the way to dinner.
In your book, you list 9 hallmarks of aging. Can you explain a few of these and tell us how to address them?
Genomic instability: DNA damage accelerates epigenetic aging and the loss of information at the epigenetic level and the genetic level causing genomic instability. We know that breaking a chromosome is the best way to accelerate aging. We’ve done this in mice and it’s not pretty. Even just a few DNA breaks can accelerate aging. To avoid breaking DNA, try to avoid using microwaves, don’t have too many x-rays done unnecessarily, or CT scans; I think CT scans are essential, but don’t have CT scans done every year just because you’re curious what’s going on inside. That’s my view. Avoid radiation of the type that will break DNA.
Deregulated nutrient sensing: This includes insulin insensitivity, Type 2 Diabetes, which is very bad for aging, probably the worst one we know of. The way to combat that is: don’t be overweight, keep exercising and lift weights.
Mitochondrial dysfunction: Mitochondria are like the battery packs in the cell; these are important for burning fat. The key points here are: the more you exercise, the more mitochondria you will have and calorie restriction boosts mitochondrial activity.
Loss of proteostasis: This is a loss of protein homeostasis due to misfolded proteins, old proteins at the cellular level. What people can do for that is to fast. Fasting a little bit is good, fasting for three days is even better at reversing misfolded proteins and inducing chaperone-mediated autophagy cellular regeneration, which helps maintain cellular proteostasis.
Telomere shortening: This will happen naturally as cells divide, but will also be accelerated by free radicals and DNA damage. I’m not a big fan of antioxidants as they haven’t done a lot in studies. But you can try to bolster the body’s natural defenses against DNA damage, which are the hormesis effects, like fasting and high intensity exercise. Also, you could use supplements like resveratrol or an NAD-booster to try to get sirtuins more active, and that seems to slow down telomere shortening; it was shown by Dr. Lenny Guarente.
How exactly does fasting promote longevity?
We found that longevity genes are turned on by fasting. They’re also turned on particularly by high intensity exercise. Being out of breath for 10 minutes every day or every other day is linked to a reduction in different diseases, certainly heart disease. My understanding is that we used to think you had to be a marathon runner to get the full benefits of exercise, but short, high intensity interval training seems to be almost as good. And the worst thing you can do for aging is to never get out of breath.
Should people start as early as possible with these anti-aging interventions, or is there an optimal age at which to begin?
Well, because we don’t yet have an epigenetic ‘reset button’ for humans, we have to be working diligently at our aging interventions to give us a chance at improving. I started when I was 30 years old, and I don’t regret it at all. Even in my 20s I was pretty good at my diet. We’ve seen in animals that if you intervene early and calorie-restrict or give them a molecule like rapamycin earlier on, it works better.
Is there a point of at which it’s impossible to turn back the aging clock?
A very old, morbid mouse will never live longer, but you can start treating them pretty late with rapamycin, I think it’s 19-20 months of age, which would be a 60-year-old human. It gets harder the older you get, so it’s better to prevent aging than to try to reverse it.
What about gender differences in aging, should we take gender into account when considering interventions?
What we’re discovering in many of the studies is that gender really makes a difference, particularly when it comes to longevity. There are treatments that work in female mice but not in males, and vice versa. And so, what this tells me is that it’s not just important to go to the doctor and get recommendation based on an ‘average’ human being, but it is way more important to get targeted recommendations, when we have knowledge about people from our own gender, our own demographic, our own age. Age is important in how we metabolize and respond to drugs. And we don’t know how we each respond to drugs because none of us is an ‘average’ human being. The only way to know is to measure it.