Sestrin: The Stress-induced Protein that Ages You in Reverse


When I was in my twenties, I made a decision to never grow old. I want to continue having birthdays — I plan to live until I’m 180. But when it comes to my body and brain, I plan to crush it like I do today, even as I’m pushing 200.

That’s why I’m pumped about new anti-aging research about sestrins — proteins that “wakes up” in the presence of stressors like low oxygen,[ref url=”″] oxidative stress,[ref url=”″] low nutrients,[ref url=””] and exposure to things that damage DNA.[ref url=”″][ref url=”″] 

When they’re activated they work a lot of anti-aging magic. Sestrins have a huge effect on how you muscles work, how your body fights tumors, cleaning your body from the inner-cells and on out, burning fat… the list goes on. Keep reading to learn about the many superpowers of sestrins.

Sestrins counteract age-related loss of muscle mass

After age 30, you lose 3-8% of muscle mass each decade, and the decline gets sharper after you turn 60.[ref url=”″] That’s why the elderly experience weakness and falls, and difficulty recovering from injury.[ref url=”″]

Conventional advice tells people to start doing resistance training to counteract muscle loss due to aging. Here’s the thing, though. If you don’t have sestrin protein in your muscles, you don’t get the full benefit of exercise. It’s a snowball effect. You lose muscle mass because you’re getting old, so you have less sestrin available to help you out. You exercise, but since you don’t have as much sestrin, so you don’t get the as much benefit from the exercise as a younger person would. Talk about frustrating.

It’s true that sestrin builds up in your muscle tissue after exercise.[ref url=”″] If you’re older and you don’t have as much sestrin, it just takes longer to see the benefit.

The answer? Supplements.

Have you ever worn a cast and found that your muscle had gone weak or even shrunk because you hadn’t used it? Researchers think that supplementing with sestrin could prevent that from happening. Having good levels of sestrins prevents muscle wasting associated with inactivity or even age.[ref url=”″]

Sestrins prevent muscle wasting by activating autophagy

If you’ve been following the blog or you’ve been listening to the Bulletproof Radio podcast for a while, you know that autophagy is your cells’ way of cleaning out waste and keeping you young from the inside out. Imagine having to drive around piles of trash and clutter every time you had to get somewhere. It would slow you down, right? Trash on the freeway during rush hour would cause annoying bottlenecks and traffic jams.

Your cells work the same way. When your cells are clear of waste and debris, they work more efficiently, so your organs and systems run more smoothly, and you feel younger.

One of the ways that sestrin proteins activate is when they sense that you don’t have enough energy from food.[ref url=””] This can happen if you restrict calories, which isn’t fun for you or anyone who has to be around you. Or, it can happen if you switch to a low-carb, high-fat, ketogenic diet like The Bulletproof Diet and you deplete your carbs (which is the goal — that’s when the magic happens).

When sestrins wake up due to low sugar and carbs, they activate autophagy so that your body burns cellular “trash” for energy instead of going after muscle tissue.[ref url=”″] Because your metabolism’s attention is diverted to cellular waste instead of muscles, the whole process prevents muscle wasting.

Sestrins suppress mTOR to preserve (and grow!) muscle

Your body has a protein called mTOR that triggers muscle building.[ref url=””] Sestrins suppress mTOR.[ref url=”″]

You’re probably wondering why suppression is a good thing. Wouldn’t you want as much mTOR as possible? Why would you want to suppress a protein that builds muscle?

It’s all about the bounceback. When you suppress mTOR, it bounces back stronger than before. Think about your breathing rate right now. You’re taking normal breaths in, normal breaths out. What happens when you hold your breath underwater a little too long? When you come up for air, you’re filling your lungs way more than you would if you were poolside in the lounge chair. It’s like that.

The cool part is, the more you suppress it, the stronger the bounceback.

Another superpower of mTOR suppression is an antioxidant effect.[ref url=”″] More on that, coming up.

Sestrins and metabolism

As any older person will tell you, one of the hallmarks of aging is that your metabolism changes. Keeping extra weight off doesn’t look the same when you’re 60 as it did when you were 20.

That’s partly because your hormone levels change. New research on sestrins is showing that they play a role, too. Scientists have been able to show that sestrin proteins regulate fat burning[ref url=””][ref url=””] and protect mice against diet-induced insulin resistance,[ref url=”″] which plays a role in not just body composition but cognitive ability, too. It has such a strong impact on metabolism that researchers are exploring its potential as a treatment for diabetes.[ref url=””]

Sestrin’s role in cell stress, oxidative stress, and cancer

Cancer is one of the four killers that I talk about in my New York Times Bestseller, Super Human. Your risk of cancer increases as you age, but that doesn’t have to be the way it plays out for you. Anti-aging science is advancing every day, and sestrins are working their way into the anti-cancer narrative.

One major way cancer forms and thrives is in the presence of reactive oxygen species (ROS), which are damaging oxygen atoms that your body produces through natural processes, or that you come into contact with by breathing polluted air, flying in an airplane, eating non-organic food… the list goes on. Free radicals can damage the DNA in healthy cells and cause them to mutate and form turmors. Further, they weaken your body’s natural mechanisms that identify and destroy tumor cells.

Your body has a lot of ways to deal with ROS. Polyphenols in food help. Your body makes glutathione, your “master antioxidant” that snaps up free radicals more efficiently than nearly any substance on the planet. Another way your body deals with ROS is with sestrin proteins. As described before in the context of muscles, sestrins suppress mTOR which through a complex pathway reduces cell damage by oxidative stress and as a result, prevents age-associated diseases.[ref url=””]

Sestrins reduce the effects of stress on cells. They “wake up” in response to cellular stress[ref url=”″] and activate response proteins that reduce cellular damage from whatever the stressor is, which increases healthy cell survival.[ref url=”″] In one study, suppression of sestrin in flies caused a buildup of oxidative damage[ref url=””] that is associated with the more unpleasant effects of aging.

Anti-tumor and anti-cancer effects of sestrins

cbd oil and cancerIts antioxidant effects have shown tangible cancer prevention benefit. Here’s what the science says:

  • Sestrin protein suppressed colon cancer in humans[ref url=””] and inhibited colon cancer tumor growth[ref url=””]
  • Sestrins caused lung cancer cells to self-destruct[ref url=”″]
  • In non small cell lung cancer, having high sestrin 2 was associated with longer overall survival than having low sestrin 2[ref url=””]

When you think of aging, what does that look like for you? Do you picture you think of wheelchairs and pill bottles? If it’s the latter, I encourage you to think of what the world looked like 50, or even 20 years ago. Things are possible now that people would have never thought would be a reality. Imagine what the world will look like 50 years from now in the world of anti-aging. It’s changing fast, and it’s going to blow our minds.

The way science and biotech are moving, you can decide what your own aging process looks like. The things you do and don’t do every day have a lot of influence on your lifespan, and what life will look like for you later on. It lights me up to be the first one to try different supplements and technologies to show you which ones actually work.





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