Cellular Housekeeping: How to Increase Autophagy and Your Healthspan

This week on the Institute for Human Optimization blog, we discuss an important subject in the world of longevity research- autophagy. Autophagy is your body’s way of clearing out damaged cells to make way for new ones. As we age, this cleaning system becomes less efficient, causing an accumulation of senescent (or “zombie”) cells that can cause inflammation and a host of other problems. Here, we’ll describe some of the science behind autophagy and what you can do to enhance this vital process and stay feeling younger longer. 

Your cells have their own busy lives inside of your body. At all hours of the day, they are eating, communicating, using energy, and taking out the trash. If your goal is to stay healthy as long as possible, you have to support the natural functions of your cells and make sure they have everything they need to keep you going.

In 2016, cell-biologist Yoshinori Ohsumi won the Nobel Prize for his many years of research on the way cells break down and recycle their contents. Thanks to this brilliant scientist, there are now over 5,000 scientific papers written about what has been termed “autophagy”.

Autophagy is the housekeeping process. When cells have reached the end of their lives or have irreparable damage, they become senescent. These senescent cells give off signals, alerting the immune system to come and clear them out and make room for healthy ones in the process. As we age, even the immune system cells start to break down and become senescent, which is why the elderly have less autophagy happening and become more prone to illness.

When our senescent cells build up, the proteins that alert the immune system (called cytokines) cause inflammation and can even damage other cells nearby. This is why the autophagy process is so essential and why longevity research covers it so heavily. Increased autophagy is one of the critical factors in having a body that functions well even in later years.

Rapamycin and mTor

Rapamycin is a term you’ll come across often when researching anti-aging literature. Originally developed as an anti-fungal compound, it was found to repress the immune system and today is used mainly for organ transplant patients to reduce the chance of rejection.

When researchers gave rapamycin to lab animals, their lifespans increased 15-25%. This unprecedented side-effect eventually led to the discovery of another important regulator in the body- mechanistic target of rapamycin or mTOR.

mTOR’s job is to determine if your body is getting enough nutrients. If you are, it flips the anabolism switch- this builds up new cells and tissues. If you’re not getting enough nutrients (fasting), it triggers autophagy instead, breaking down old cells and recycling the proteins for future use.

Rapamycin was found to not only inhibit the immune system cells but also inhibit mTOR. That means your body reacts as though you’re in a fasted state even though you might not be. This triggers autophagy and could be the reason for the longer lifespans in the animals given the compound in lab studies.

There are no studies yet that show rapamycin’s effect on the human lifespan, but there are things you can do to inhibit mTOR and increase autophagy yourself.

Intermittent Fasting

Now that you understand the basics of how autophagy works, you can start to hack your body to achieve the results you want. One of the best ways to naturally inhibit mTOR and get that housekeeping process going is intermittent fasting.

Intermittent fasting, or IF, means becoming conscious of the times you choose to eat and increasing the time you’re not consuming calories. It can also be termed “time-restricted eating.”

Valter Longo, Director of the Longevity Research Institute, helped popularize what he calls a “fasting-mimicking diet”. His research showed that mice that fasted intermittently had improved life spans, reduced inflammation, increased cognitive ability, and that this mechanism could be used in humans for similar results.

Autophagy is hard to measure outside of a lab, but most experts agree that it initiates in humans after 18-20 hours of fasting with maximum benefits happening around the 48-hour mark. When you’re not consuming calories, mTOR flips the autophagy switch, putting your body in a cleanup mode and getting rid of the cellular waste that can build up and cause health issues. Many people who practice intermittent fasting as a health hack report having more energy during the day, fewer cravings, clearer skin, and weight loss. 

There are a variety of apps that can help you track your fasts, remind you when to eat, and provide more information on how to benefit from this practice.


Berberine is an alkaloid compound naturally occurring in a variety of plants such as the Oregon grape, Californian poppy, and cork tree. Though it has a long history of being used in traditional Chinese and Indian medicine, it is being researched today for its pharmacological effects against chronic health conditions such as depression, gastrointestinal disorders, neurodegenerative diseases, and more. It has also been shown to have anti-aging properties in rodent studies.

Naturally-aged mice that were given berberine lived about 17% longer than their counterparts and experienced positive changes in their fur density, behavior, and healthspan.

The main driver of berberine’s success as an anti-aging compound revolves around its activation of AMPK (adenosine monophosphate-activated protein kinase). AMPK’s main job is to monitor cellular energy and determine if your cells are operating efficiently. If AMPK is not activated, it can’t do its job, and damaged cells can fall through the cracks, ultimately avoiding getting cleared out by autophagy.

Berberine has also been found to reduce blood sugar levels in people with type-2 diabetes. Lowering blood sugar is essential for metabolic health and can do a lot towards increasing your overall healthspan. Berberine is currently available on the market, but please speak with your physician before starting any supplement regimen and use a company that is reputable for quality.

(Here is a great article on berberine by Dr. Rhonda Patrick if you’d like to learn more.)

When it comes to longevity, autophagy is the MVP. We can’t have zombie cells floating around in our bodies, causing upregulation of cytokines and all the damage that comes with them. Instead, we can work with our cells, giving them everything they need to take out the trash and make room for new, healthy cells to thrive.

Through intermittent fasting and using natural compounds like berberine, we can take active steps to increase our health spans and feel amazing well into old age. Autophagy will be an encompassing theme for this blog and future projects as we strive to bring you the latest information on optimizing human health.

If you’re interested in becoming a patient of the Institute for Human Optimization, schedule a discovery call and let’s discuss what we can do to hack your lifestyle to improve your healthspan.

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