Exercise Better Than Fasting for Supporting Autophagy, Longevity and Health

by Mike Mutzel


A new book dedicated to the topic of exercise as an autophagy enhancer makes the case that physical activity is a very important inducer of autophagy–especially in muscle, heart, liver and brain.

We review key takeaways from this book and discuss blending fasting and exercise to support longevity and the biology of aging.






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Book Review:

Chen, N. (2021). Exercise, Autophagy and Chronic Diseases. (N. Chen, Ed.) (pp. 1–267). Springer. 978-981-16-4524-2


Related: Is Exercise: Better Than Fasting, Calorie Restriction for Aging, Longevity?



Time Stamps:

01:14 If you are not exercising at all, you may need to increase your fasting duration and intensity. If you are doing lots of exercise, fasting may not be as important.

01:53 Autophagy is the self-degradative process that targets cell constituents, like mitochondria, that are damaged or aged. One of the hallmarks of aging is misfolded protein accumulation. This causes cells to misbehave and potentially trigger apoptosis, leading to disease and disfunction within organ systems.

02:28 Autophagy occurs at low levels in most tissues, leading to the routine turnover of cellular trash and supporting the maintenance of homeostasis.

02:36 Dysfunctional autophagy leads to many acute and chronic diseases, like obesity, type 2 diabetes, non-alcoholic fatty liver disease, cancer, neurodegenerative disease, cardiovascular disease and more.

03:00 Providing periodic states of nutrient deprivation can be achieved by exercise, fasting or caloric restriction. This allows the turnover of cellular trash.

03:45 Acute (one time) and chronic exercise (done near-daily as routine) are enhancers of autophagy. There are differing adaptations in the post exercise window. There are long-term favorable adaptations with habitual exercise.

04:35 Appropriate exercise can regulate autophagic activity through multiple signaling pathways. Moderate exercise can promote cellular autophagy.

04:50 Over training may lead to over accelerated autophagy, and even cause programmed cellular lesions or cell death.

05:35 Autophagy is important in the maintenance of skeletal muscle mass and function. Skeletal muscle mass is about 40% of your body weight.

06:30 Autophagy is part of your muscle’s adaptation process. Exercise tears down muscles and places a hermetic stress on your cardiovascular system.

07:30 Heart muscle is highly influenced by autophagy. Misfolded proteins and mitochondrial dysfunction within the heart can lead to challenges in functionality.

09:00 Autophagy influences the health of the heart, brain, muscles and liver.

11:15 Moderate exercise increases heart autophagy levels and degrades intracellular metabolic waste, helping to maintain the health of heart cells. It has been shown to improve injured cardiac functioning cells and degrade intracellular proteins that are compromising ejection fraction and heart health. Morning fasted exercise upregulates glycogen depletion and can increase levels of autophagy.

12:40 Ageing cardiac myocytes are prone to reduced autophagy. Long-term aerobic exercise can increase autophagy levels in ageing cardio myocytes, resisting myocardial ageing.

13:40 Fatty liver is a sign of dysregulated autophagy. Hepatocytes are the cells of your liver. Autophagy impacts the health of your liver. The level of fat buildup in your liver is measurable with a liver function test: ALT, AST and GGT.

16:15 Glycogen levels in your muscle before exercise is correlated in the flux in autophagy.

18:10 Exercise can induce autophagy and increase the expression of autophagy-related proteins in normal cells. Long-term endurance exercise can increase cellular levels and improve adaptation of the body to exercise training, by upregulated initiation proteins, LC3 and Beclin-1.

18:55 Chronic exercise induces autophagy and increases basil levels, over acute exercise.

19:40 Autophagy impacts mitochondrial biogenesis and function. As you age, the level of quality mitochondria within your heart cells can decline.

20:55 Moderate intensity long-term exercise can effectively improve the quality and quantity of myocardial mitochondria and reduce the number of damaged or ageing mitochondria in order to meet functional demand.

22:12 Exercise may play a therapeutic role in protecting against mitochondrial impairment and insulin resistance. Exercise helps to maintain mitochondrial health in the muscle, where type 2 diabetes often starts. Part of the way moderate exercise improves mitochondrial function is autophagy mediated.

23:25 Autophagy is part of the balance between muscle protein synthesis and protein degradation.

24:00 Hyperglycemia, insulin resistance and type 2 diabetes can decrease skeletal muscle mass and induce skeletal muscle atrophy and dysfunction.  Insulin resistance accelerates muscle loss and muscle wasting.

25:25 A high fat diet or high sugar diet can lead to dysfunctional muscle and decrease grip strength. Autophagy is required to maintain skeletal muscle mass and protect against atrophy.

26:14 Lipophagy is the process of liberating stored fat from your fat cells. Lipophagy and mitophagy can reduce oxidative stress and prevent the overaccumulation of lipids within the cell. Autophagy is dysregulated in obese individuals.


  1. Maybe is time to stop bashing cardio and recognise its benefits? Both cardio AND resistance training are needed. And they need to be at the right ratio.

    Hiking is great for many things, but cardio it isn’t. Its training effect is more muscular endurance. Take it from a mountain guide: unless you’re at high altitude, you are not limited by the oxygen (aerobic metabolism) but rather localised muscles fatigue (ATP turnover and lactate clearance).

    It isn’t a replacement for sub AeT intensity, long duration type workout. Mitochondria can be increased in number, size and/or function as adaptation to different type of workouts. Strength training alone doesn’t hit them all.

    It is about training all the systems for optimal adaptation.

    • Hi Jonathan,

      Didn’t realize I was “bashing” cardio. Of course it has benefits! Both are needed, 100% agree.

  2. Hi Mike, thanks for this great talk. I am interested in the bloodwork cheat sheet you mentioned. Where can I find it?

  3. Do you have a document that shows optimal blood testing levels? I just got a full blood panel and what to look at optimal reference ranges. Thanks in advance for all your helpful information.

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