Fasting Triggers Autophagy, The Key To A Longer Life


The scientific and medical community are just beginning to understand the significance autophagy plays in avoiding disease and living a long, healthy life. The best way to make sure you’re reaping all its benefits? A regular fasting protocol.

Autophagy and How Fasting Contributes To Longevity

There are many benefits to fasting and autophagy. And while weight reduction/management might be the first to come to mind, longevity is what has much of the health community most excited.

The Science of Autophagy

To understand the benefits of fasting, we must first break down the benefits of autophagy. Autophagy, derived Greek meaning “self” (auto), and “eating” phagy -- literally describes “self-eating.” An easier way to understand it, however, would be to describe it more as ‘self-cleaning” on the cellular level.

During autophagy, the body (temporarily starved of nutrients from calories/sugar) begins the use of old/damaged cellular components for re-use and recycling. This does an excellent job of cleaning up disease-causing cellular abnormalities. This involves the formation of something called an autophagosome, which destroys damaged/unnecessary cellular components including misfolded proteins, damaged organelles, and invading pathogens (disease)..

Think of it as a spring cleaning for your cellular system. Without these clean-ups, junk and unwanted pieces begin to accumulate. With a constant influx of calories and sugar, the body has no route to rid itself of these disease-causing cells.

Activation by Fasting

Now that we’ve explored the science of what autophagy is, now time to dive into how to get there. Fasting (calorie restriction) is the best way to trigger autophagy. When nutrients are scarce, the body needs to use existing cellular resources in an efficient manner. Breaking down cellular components to reuse the mechanism that ensues. Through this process, the useful parts of the cell are reused and the potential harmful parts are cleaned up.

Role in Health and Longevity

Relatively new breakthroughs in science reveal that autophagy is essential for cellular health and homeostasis. It is therefore a crucial element to longevity, observed in an array of organisms from worms to humans. (1) Without it, the body accumulates damaged proteins and organelles which contribute to various cancers, neurodegenerative disorders, and heart disease. It is the incidence of these damaged cells, disease, and organ/system failure that ultimately lead to death or reliance on intervention. If able to delay these failures as long as possible, the human lifespan becomes much longer and more enjoyable with a healthy body and mind.

Ongoing Research

As the mechanisms of autophagy are now widely accepted, much current research is focusing on protocols related to specific concerns such as cancer treatment and preventing age-related kidney deterioration. (2) While targeted approaches may be hugely beneficial in therapeutic clinical settings, the broad learnings are clear enough to apply to the general population. Simply stated, fasting is a tool available to everyone and barring contraindications like a history of eating disorder or malnutrition, and should be leveraged accordingly.

Fasting Activates Autophagy

Autophagy begins when your body runs out of sugar, or nutrients it can convert to sugar, to create energy. The most straightforward way to activate autophagy is to fast, either intermittently (IF) or for longer durations as periodic long fasts (PF). (3) Depending on a host of bioindividual factors, including what you’ve eaten prior and the way your metabolism works, autophagy can be triggered somewhere in the 12-36 hour range (longer ranges more likely). Studies also find a gap between the starting point of autophagy and the “peak,” where your body is doing more heavy lifting for cellular cleaning. Some studies have also observed diets very low in sugar, moderate in protein, and high in fat may kick off autophagy by initiating ketosis. (4)

Benefits of Fasting for a Longer Life

  • Autophagy
    • Cellular cleaning is key for optimal health and disease prevention. Given fasting is the absolute best way to trigger autophagy, it is a no-brainer in a longevity-focused lifestyle.
  • Hunger Management
    • So many people struggle with their relationship with food and hunger, and without fault - the standard American diet (SAD) has knocked hunger cues so out of whack, it’s nearly impossible to eat intuitively at an optimal amount. Fasting is a very effective way to get hunger signals regulated.
  • Weight Management
    • Inherent in a fast is a reduction of calories, which in itself can lead to weight loss and management. Even more, though, is the promising effects fasting has on the metabolic system as a whole, helping the body process food and nutrients without holding onto excess fat stores.
  • Mental Clarity
    • Fasting supports neuroplasticity and decreases inflammation, a double win for brain health and cognitive function. Fasting practitioners often report significant mental clarity improvements as being one of its most immediate benefits. There is also promising research indicating it may be effective in reducing incidence of and slowing progress of Parkinson’s and Alzheimer’s disease. (5)
  • Gut Health
    • Fasting is an extraordinary tool in healing the gut microbiome. Because of its anti-inflammatory and gut microbiota-enhancing, combined with its impact on metabolism, it is a key part of a gut health protocol for many of my patients.
  • Decision-Fatigue Freedom
    • The burden of healthy food choices 3-9 times a day is often a struggle I hear from patients. In the case of intermittent fasting, the required choices made each day are lowered drastically, leading to less decision fatigue and higher likelihood of overall success. And in the case of a prolonged fast, the decision-fatigue is essentially eliminated. There is no meal-prep or expensive input required to make a lasting impact on your health.

The Longevity Diet to Pair with Your Fasting Regimen

While fasting is an extraordinary tool as part of a longevity-focused lifestyle, you cannot out-fast an otherwise poor diet and lifestyle. Focusing on ketosis as you approach your diet is one way to think about a holistic diet. But truly tackling longevity will probably mean something different per individual. Whether you’re focused on weight loss, autoimmune function, blood sugar, or food sensitivities, the perfect diet for you will be best identified working with an expert.

There is no one-size-fits-all protocol when it comes to fasting. There are many ways to achieve autophagy based on what fits your nutritional needs, preferences, lifestyle, and schedule the best.

  • Intermittent Fasting (daily window) 
    • The most popular way to intermittent fast is choosing a daily window to fast during--an example being 8pm to noon the following day. And easier way to think about it is your eating window, which in the same example would be noon to 8pm. The most common recommendations are 14 hours daily for women and 16 hours daily for men.
  • Intermittent Fasting (OMAD)
    • Another way to fast is called One Meal A Day, or OMAD. This structure leans on a bigger fasting window. The benefits of this structure is that you really only need to think about preparing and eating one meal during the day, and it leaves a ton of flexibility for social events or meals where you may want to consume many calories.
  • Alternate Day Fasting 
    • Another approach is to take either the intermittent or OMAD protocol and apply it every other day. This is a good approach for someone who may not otherwise get enough nutrition and calories.
  • 5:2 Fasting
    • Some people take a 5:2 approach, which is eating normally 5 days of the week and eating less than 500 calories per day on the remaining 2 days.
  • Periodic Fasting
    • Periodic fasting refers to fasting that is not on a daily or weekly basis, but part of a longer term health strategy that may include longer, prolonged fasts.
  • Fasting Mimicking
    • Similar to the 500/calorie days on the 5:2 fast, there is an approach called “fasting mimicking” which restricts calories and delicately balanced macronutrient ratios enough to mimic the effects of fasting to trigger autophagy without actually fasting. This requires a prescriptive and precise diet regime guided by an expert.

As one of the first functional medicine telehealth clinics in the world, we provide webcam health consultations for people around the globe.


The autophagy triggered by intermittent fasting not only has the potential to prevent age-related decline, but may also reverse some of the negative effects of aging such as disease and system decline.

There is no clear evidence supporting one protocol over another. The answer to this is best answered on an individual level to see which approach best fits someone’s health needs and lifestyle requirements.

Telomere length may be improved by the effects of intermittent fasting.

During a fast I recommend adding 6 grams of branched-chain amino-acid supplements (BCAAs), as a powder or capsule supplement. These can help improve the positive impact of fasting and reduce unwanted side effects like fatigue and hunger.

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  1. Nakamura S, Yoshimori T. Autophagy and Longevity. Mol Cells. 2018 Jan 31;41(1):65-72. doi: 10.14348/molcells.2018.2333. Epub 2018 Jan 23. PMID: 29370695; PMCID: PMC5792715.
  2. Mohammad Bagherniya, Alexandra E. Butler, George E. Barreto, Amirhossein Sahebkar, The effect of fasting or calorie restriction on autophagy induction: A review of the literature, Ageing Research Reviews, Volume 47, 2018.
  3. Longo VD, Di Tano M, Mattson MP, Guidi N. Intermittent and periodic fasting, longevity and disease. Nat Aging. 2021 Jan;1(1):47-59. doi: 10.1038/s43587-020-00013-3. Epub 2021 Jan 14. PMID: 35310455; PMCID: PMC8932957.
  4. Daniela Liśkiewicz, Arkadiusz Liśkiewicz, Mateusz Grabowski, Marta Maria Nowacka-Chmielewska, Konstancja Jabłońska, Anna Wojakowska, Łukasz Marczak, Jarosław J. Barski, Andrzej Małecki, Upregulation of hepatic autophagy under nutritional ketosis, The Journal of Nutritional Biochemistry.
  5. Roco-Videla, Á., Villota-Arcos, C., Pino-Astorga, C., Mendoza-Puga, D., Bittner-Ortega, M., & Corbeaux-Ascui, T. (2023). Intermittent Fasting and Reduction of Inflammatory Response in a Patient with Ulcerative Colitis. Medicina, 59(8), 1453.

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Dr. Will Cole, DNM, IFMCP, DC is a leading functional medicine expert who consults people around the globe, starting one of the first functional medicine telehealth centers in the world. Named one of the top 50 functional and integrative doctors in the nation, Dr. Will Cole provides a functional medicine approach for thyroid issues, autoimmune conditions, hormonal imbalances, digestive disorders, and brain problems. He is also the host of the popular The Art of Being Well podcast and the New York Times bestselling author of Intuitive Fasting, Ketotarian, Gut Feelings, and The Inflammation Spectrum.

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