How to Stimulate Autophagy to Dramatically Improve Your Health
You can stimulate autophagy by fasting for three days. If you’re not up to that, learn what else you can do to get rid of the scenescent zombie cells that age you and promotes chronic disease.
The best way to stimulate autophagy is to not eat for a certain period of time, like around three days. There’s an obvious problem with that — most people won’t do it, because of the discomfort of hunger.
Another reason most people won’t fast long enough to stimulate autophagy is because the feedback loop of cause and effect is weak; meaning that it’s hard to know in the short-term what all that hunger is getting you. It’s not like your health is immediately and obviously transformed once autophagy kicks in. No, it takes time and many rounds of stimulating autophagy for its benefits to be noted.
As I wrote in the post How Intermittent Fasting Ignites Cellular Autophagy and A Longer, Healthier Life, cellular autophagy is a crucial process for cells to survive and stay healthy. During a period of ingesting limited calories, or starvation, not only do cells break down proteins and nonessential components and reuse them for energy, but also cells use autophagy to:
- Destroy invading viruses and bacteria; and
- Rid themselves of damaged structures; a process which…
- Is thought to get disrupted in cancer, infectious diseases, immunological diseases and neurodegenerative disorders; including Parkinson’s disease, type 2 diabetes and cancer.
One more thing – disruptions in autophagy are also thought to play a role in aging; conversely, improved autophagy is thought to slow down the aging process.
Autophagy was a big topic discussed in last week’s post where I delved into numerologists Dr. Andrew Huberman’s video interview with geneticist Dr. David Sinclair. Several Subscribers to this blog wrote me to ask if I could go deeper into how to stimulate autophagy, particularly as it relates to hormesis, another topic that loomed large in the interview.
If you’re interested in extending your healthspan, and possibly your lifespan as well, learning how to stimulate autophagy and target hormetic pathways are essential.
How to stimulate autophagy and target hormetic pathways can be difficult to clearly describe, because the science is still evolving in these areas. Thankfully, we have the benefit of a recent Longevity Roadmap email sent by Dr. Mark Hyman (no link available) that’s right on the mark, as well as a post by the Center for Healing Nuerology to help guide us.
So, let’s dig in.
The Damage Done by Zombie Cells
Zombie cells is a term given to senescent cells, which are cells that are no longer fully alive, nor dead. In this zombie state they secrete proinflammatory cytokines that weaken nearby cells, and promote various chronic illnesses, as well as to accelerate biological aging.
The process of autophagy helps eliminate senescent (zombie) cells, and is thereby a very important arrow in your arsenal to slow down the aging rate.
This house is a mess!
A few years ago, I came up with a metaphor to conceptualize cellular autophagy. The cells are represented by a house, and the dirt and clutter in the house represents the cellular debris and waste byproducts that accumulate in cells. If your house gets to dirty and messy, it’s hard to function in it, and so it is with your cells. Now, if it’s just you in the house and you’re tidy, just a bit of cleaning here and there will suffice. But after a party, the house is a mess, and you need to do some heavy cleaning. So it is with autophagy — if you exercise regularly, aren’t too stressed, get restorative sleep, and eat a nutritious diet, your body can clean up the cells without much assistance; however, Spring Cleaning is always recommended.
Autophagy and apoptosis
There are two main mechanisms of cellular clean-up: autophagy and apoptosis. As mentioned, autophagy is our cells’ way of housekeeping—it cleans up any debris or damaged organelles within the cell to preserve its life. When a cell is damaged beyond repair, that’s where apoptosis, or programmed cell death, comes in. Apoptosis targets the damaged cell and destroys it.
Aging Takes A Hit On Our Cellular Quality Control
A lifetime of eating nutrient-poor processed foods, living a sedentary lifestyle, experiencing chronic stress, and exposing ourselves to chemical toxins and electromagnetic frequencies (EMFs) from smartphones, electricity, and appliances takes a toll on our cells ability to stimulate autophagy to deal with scenescent cell proliferation.
As a result, there is a buildup of inflammation and oxidative stress that damages our DNA, shortens our telomeres, and causes advanced aging. Experts refer to this accelerated aging process due to modern-day living as “inflammaging.”
Our body’s ability to endogenously stimulate autophagy loses efficacy as we age, and then damaged cells like senescent cells become less efficiently removed from our organ tissues. They can stick around and secrete harmful pro-inflammatory cytokines that infect and injure nearby cells, turning them senescent.
These zombie cells are found in many age-related chronic diseases. The joints, arteries, eyes, liver, and brain are most impacted, which is why zombie cells are frequently observed in osteoarthritis, cardiovascular disease, cataracts, fatty liver, cancer, and Alzheimer’s disease.
The good news is that you can do something to stimulate autophagy in order to kill off zombie cells.
Stimulate Autophagy by Targeting Hormetic Pathways
Not all stress is bad.
Yes, the stress that affects you emotionally, or behaviorally, is pretty bad, unless it moves you to take corrective actions that improve the quality of your life. Which brings us to hormesis, the good side of stress.
Stress can be extremely beneficial in small doses that stimulate a certain, positive response. Hormesis is a small dose of a stressor that causes your body to adapt and become stronger—and live longer. Exercise is a classic example of hormesis: low-level damage to your muscle fibers causes them to build back stronger. In fact, exercise is about the best anti-aging thing you can do, as I report in Longevity Exercise: 7 Anti-aging Interventions Backed By Science.
When senescent cells linger, they secrete proinflammatory cytokines that cause damage to nearby cells and tissue. As we get older, autophagy and apoptosis lose their stamina, and zombie cells start to accumulate. Activating hormetic pathways can help prevent zombie cells from taking over by lowering inflammation and turning on longevity genes. It’s like the saying goes: what doesn’t kill you makes you stronger.
Starting with exercise, here are a handful of ways you can use to activate autophagy and rid yourself of excess senescent cells.
Exercise in the form of resistance and cardiovascular training reduces markers of inflammation and cellular aging.
Resistance training prevents age-related sarcopenia (muscle wasting) and osteoporosis. Because weight training causes slight tears in the muscle tissue (this is its hormetic effect), eat high-quality protein (about 1.2 g/kg/day) after workouts and give yourself proper rest periods in between sessions to enable muscle recovery — this is when the muscle and strength is built.
Aerobic and anaerobic exercise enhances insulin sensitivity, lowers inflammation, and increases your heart rate variability (HRV), a biomarker of healthy aging. Having a high HRV is associated with fewer inflammatory cytokines and zombie cells.
Fasting promotes autophagy and inhibits mTOR (mammalian target of rapamycin), a metabolic pathway that upregulates cell growth and proliferation, which protects against cancer. Fasting also stimulates mitochondria production and energy metabolism. There are two main types of fasting practices that you should consider trying in order to enjoy the health benefits conferred by fasting.
Intermittent Fasting (IF), or “time restricted eating”, is when you abstain from eating and drinking (other than black coffee, herbal tea and water) for 16+ hours. Typically, this is done from early evening till midday the following day. There’s also the popular “5:2” plan, whereby you eat normally for five of seven days, and eat just 500 to 800 calories for two days.
I’ve written a lot about Intermittent Fasting, which you may access here.
The ProLon Fasting Mimicking Diet was invented by Dr. Valter Longo, and consists of precise amounts of micro and macronutrients that, in effect, fools the body into thinking it’s fasting, and thereby stimulate cellular longevity pathways.
You may learn all about ProLon FMD on this page, where I include a video of me guiding my mother through one week on the fasting diet.
Polyphenols and Supplements
As mentioned, certain hormetic stressors can kill zombie cells. Below are some approached to activate hormesis and eradicate disease-causing zombie cells.
Polyphenols are plants’ defense mechanisms that deter predators from eating them due to their bitter or strong taste. In humans, polyphenols are metabolized by our gut microbiota into bioactive metabolites that promote the growth of beneficial gut microbes and activate genes that combat inflammation.
Here are four of the most widely researched polyphenols that you can obtain and consume as supplements:
Resveratrol: lowers inflammation, prevents cancer and the formation of zombie cells by turning on the SIRT1 longevity gene. Red wine is a classic source, but you would have to drink extraordinary amounts to get close to obtaining any benefits. A concentrated resveratrol supplement in the trans-resveratrol form is the best way to get it.
Update (9/20/21): There's some controversy about the benefits of resveratrol. If you currently use resveratrol, or are considering it, make sure you read my update.
Curcumin is a potent antioxidant that supports joint, gut, hepatic, and cardiovascular health. You can get curcumin, the bioactive molecule in turmeric, by making your own curry dish, a healthy shake, or taking it in supplement form.
Quercetin: prevents disease through its extensive health-promoting, anti-aging properties. Supplementation also effectively reduces viral replication in COVID-19. Capers, peppers, onions, and apples are natural sources.
Epigallocatechin-3-gallate (EGCG for short) is the most abundant and biologically active catechin in green tea and matcha (my preference). It supports gut health and has anti-obesity and anti-cancer properties. You can also take it as a supplement.
Spermidine is a naturally occurring polyamine (an organic compound having more than two amino groups) that triggers autophagy, notwithstanding its unsavory-sounding name.
In my post, The Geroprotectors: 7 Anti-aging Interventions Backed By Science, I make the following science-backed claims:
- Spermidine is associated with lifespan extension when supplemented in the food supply of yeast, flies, and worms.
- Spermidine concentrations in the body (endogenous) decrease as the organism age, including in humans with the exception of centenarians. Acute injections of spermidine in mice activate autophagy in multiple organs, while chronic spermidine feeding promotes increase in healthspan.
- Given that spermidine increases autophagy, it’s unsurprising that the result is improved healthspan. Dr. Yoshinori Ohsumi won a Nobel Prize for showing how cellular autophagy detoxifies and repairs cells, thereby making them healthier.
In addition to upregulating autophagy, spermidine:
- Can impede a number of neurological pathologies and induce neuronal autophagy (in nerve cells).
- Can extend lifespan in two short-lived mouse models after oral administration of spermidine.
For your convenience, I embedded a video about spermidine below. You can learn more about this supplement in my post, How Spermidine-rich Foods Feed A Healthy Aging Brain.
Your Takeaway On Stimulating Autophagy
Remember these three things:
- Cellular autophagy is your body’s natural cellular clean up mechanism that’s necessary for healthy cells; the primary function being to kill zombie (scenescent) cells that accelerate aging and chronic diseases.
- Fasting is the best way to stimulate autophagy, but it takes about three days for a substantial response. Ideally, you will work up to a long fast, beginning with Intermittent Fasting, then a full day fast, etc.
- In addition to fasting, you can simulate autophagy via exercise, and by consuming the polyphenols and supplements listed above.