If you want to know how fasting improves mitochondrial function, then this article about intermittent fasting and mitochondria is just for you.

Mitochondrial Powerplants

Your body is comprised of trillions of cells, bacterial life forms, organelles, and mitochondria. All of them enable you to survive and exist in the first place.

Mitochondria are small organelles inside the cells that function like the powerplants of the cells. They help to create a molecule called adenosine triphosphate (ATP), which is the energy currency of your cells.

The mitochondria play a critical role in cellular senescence and overall longevity[i]. They literally make your body sustain itself by converting calories, sunlight, and oxygen into ATP.

Your cells are constantly monitoring the nutrient status around them as to choose whether to replicate or preserve energy by recycling themselves. That regulation is mediated by the electron ratios of NAD+ and NADH, which are enzymes of energy homeostasis and ATP production.

Fasting and Mitophagy

The mitochondria are constantly breaking apart and combining together with each other through fission fusion processes[ii]. This type of mitochondrial dynamics is necessary for maintaining the health and vitality of the cells. Poorly functioning mitochondria can produce more free radicals and create oxidative stress throughout the entire body.

When dysfunctional mitochondria get broken down they’ll get eaten up by other healthy organelles and they’re recycled back into energy. This type of self-eating is called mitophagy or mitochondrial autophagy.

Defective mitochondria are linked to many diseases of excessive growth, such as neurodegeneration, diabetes, obesity, and cancer.

The key to keeping mitochondria healthy is to maintain energy homeostasis and remove dysfunctional cellular components that are causing inflammation.

Time-controlled fasting prevents mitochondrial aging and deterioration[iii]. It can also promote the longevity of mitochondria by eliminating the production of reactive oxygen species and free radicals by dysfunctional organelles[iv].

When your body faces a shortage of energy whether through caloric restriction, fasting, starvation, or anything the like, then you’re going to promote the fusion of mitochondria.

Fasting Keeps the Mitochondria Healthy

Fasting enhances mitochondrial coordination through peroxisomes, which are a type of organelle that increase fatty acid oxidation.

A study published in Cell discovered that fasting and caloric restriction substantially increased the lifespan of nematodes by promoting mitophagic mitochondrial fission fusion dynamics[v].

One of the scientists William Mair said: “Our work shows how crucial the plasticity of mitochondria networks is for the benefits of fasting. If we lock mitochondria in one state, we completely block the effects of fasting or dietary restriction on longevity.”

If the cells detect the presence of any nutrients, autophagy gets suppressed due to the elevation of growth factors such as insulin, IGF-1, and mTOR. Therefore, the key is to elevate fuel sensors of energy preservation such as AMPK and lower mTOR, which can be accomplished with strict intermittent fasting.

Fasting and caloric restriction promote mitochondrial efficiency by fusing together several mitochondria. Nutrient excess in the eating phase fragments the mitochondria and decreases their ability to produce energy.

Check out this article on how fasting can make you live longer by promoting mitochondrial function!

Does Fasting Increase Mitochondria Biogenesis

Building new mitochondria is also critical for keeping yourself youthful and energized throughout your lifetime.

Mitochondrial biogenesis is the process of building new mitochondria through the activities of certain metabolic regulators such as PGC-1alpha[vi] and AMPK[vii]. AMPK produces new mitochondria and controls mitophagy as well.

The key to growing new mitochondria is to signal the body to produce energy under energy depletion and in stressful environments. This causes cellular crises that need to be compensated for by building new powerplants.

Fasting increases AMPK which promotes fatty acid oxidation which produces ketone bodies [viii]. The mitochondria run a lot better on ketone bodies because they can get into the mitochondria faster via the electron transport chain and they’ll yield more ATP than glucose.

[viii]. The mitochondria run a lot better on ketone bodies because they can get into the mitochondria faster via the electron transport chain and they’ll yield more ATP than glucose. Fasting increases FOXO proteins , which are transcription factors that regulate longevity through the insulin and IGF-1 pathway. FOXO1 and FOXO3 promote mitophagy[ix]

, which are transcription factors that regulate longevity through the insulin and IGF-1 pathway. FOXO1 and FOXO3 promote mitophagy[ix] Fasting increases sirtuins, which are a family of proteins that act as metabolic sensors. SIRT1 regulates mitochondrial biogenesis and PGC-1alpha[x]. Sirtuins regulate fat and glucose metabolism in response to physiological changes in energy levels, thus they’re crucial determinants of energy homeostasis and healthspan of the cell[xi]. Suppressing SIRT2 restricts fatty acid metabolism, reduces mitochondrial activity, and promotes obesity[xii].

The key to increased mitochondrial biogenesis and longevity is to prime the body towards a more fat burning metabolism. This increases your cells’ ability to produce energy from its own internal resources (autophagy) and lowers insulin levels (less oxidative stress).

Fasting Increases Mitochondrial Function

But intermittent fasting increases mitochondrial functioning in many other aspects as well.

Mitochondrial density refers to the cells’ ability to produce more energy from fewer resources and become more efficient at it.

Fasting increases NAD+ levels, which is an enzyme that helps with energy production and promotes longevity. NAD+ support mitochondrial functioning during youth and restore it in later life[xiii] NAD+ protects the cells against oxidative stress with the help of sirtuins [xiv] . NAD+ activates sirtuins which then help to grow blood vessels and muscle [xv] NAD+ replenishment improves lifespan and healthspan through mitophagy and DNA repair [xvi] . NAD+ supplementation can promote DNA repair in mice [xvii]

and promotes longevity. Intermittent fasting protects against telomere shortening and DNA damage. Telomeres are protective caps on top of chromosomes that shorten as you age.

Telomeres are protective caps on top of chromosomes that shorten as you age. Fasting increases sirtuins, which promote fat burning and mitochondrial functioning. SIRT3 is the major mitochondrial deacetylase and it protects against oxidative stress[xviii] through its anti-oxidant properties. SIRT1 overexpression inhibits telomere deterioration while its inhibition accelerates telomere shortening[xix].

Burning fatty acids and ketones cause less damage to the mitochondria as well. Glycolysis, which is the process by which mitochondria burn glucose, causes more oxidative stress and the creation of free radicals, which in turn will speed up aging.

Glycolysis, which is the process by which mitochondria burn glucose, causes more oxidative stress and the creation of free radicals, which in turn will speed up aging. Reactive oxygen species and oxidative stress activate FOXO pathway to adapt to the stress. Fasting causes mild stress that makes the body adapt to it through hormesis. Inactivity of FOXO factors accelerates atherosclerosis and compromises stem cell proliferation[xx].

As you age or when you experience high levels of stress, you become more prone to mitochondrial dysfunction and accelerated aging. Mechanisms mediated by fasting such as increased NAD+, sirtuins, and FOXO proteins make your cells more resilient against environmental stressors and energy depletion.

Fasted Cardio Mitochondria

Next to fasting, exercise can also increase mitochondrial biogenesis and function through the same pathways of AMPK and FOXO proteins.

High-intensity interval training increases the ability of mitochondria to produce energy by 69% in older people and 49% in younger[xxi].

Even just acute exercise increases FOXO1 phosphorylation, improves insulin sensitivity and promotes mitochondrial biogenesis[xxii]. Exercise also increases NAD+ and sirtuins[xxiii][xxiv]

However, to see the real growth you have to send a real signal. That’s why it’s a good idea to incorporate both low-intensity aerobic exercise and high-intensity training.

Staying under the glycolytic zone of your VO2 max makes you burn more fatty acids instead of glucose. This range is great for promoting mitochondrial biogenesis if done over a long period of time. It builds up your fat burning engine so to say.

Anaerobic training where your heart rate exceeds 70% of your VO2 max makes you burn glycogen and enforces mitochondrial density. It makes your muscles produce more ATP at a quicker rate and within a shorter time.

How much training of each you do depends on your goals and workout routine but it’s a good idea to add at least 1-2 sessions of each into your week.

Doing fasted exercise will have a much greater effect on mitochondrial biogenesis and adaptation because you’re forced to produce more energy while being completely depleted of it. This also raises a lot more growth hormone and drives you deeper into ketosis.

Fasting for Mitochondria

Here’s how to do intermittent fasting for mitochondria:

Practice daily intermittent fasting and consume fewer calories. Caloric restriction and fasting increase SIRT3 and deacetylate many mitochondrial proteins[xxv]. Reduction of calorie intake without causing malnutrition is the only known intervention that increases the lifespan of many species including primates[xxvi][xxvii]. It’s thought that these effects in longevity require SIRT1[xxviii].

Caloric restriction and fasting increase SIRT3 and deacetylate many mitochondrial proteins[xxv]. Reduction of calorie intake without causing malnutrition is the only known intervention that increases the lifespan of many species including primates[xxvi][xxvii]. It’s thought that these effects in longevity require SIRT1[xxviii]. Lower your carbohydrate intake strategically. Glucose depletion results in increased NAD+ by promoting AMPK and SIRT1 activity[xxix]. Ketone bodies lower the production of reactive oxygen species in mitochondria by increasing NADH oxidation into NAD+[xxx]. A ketogenic diet promotes NAD+ levels because of fatty acid oxidation and glucose depletion[xxxi]. However, fruit can also activate enzymes that help to convert NADH into NAD+[xxxii]. So, some natural fruit can be good even on a low carb diet.

Glucose depletion results in increased NAD+ by promoting AMPK and SIRT1 activity[xxix]. Ketone bodies lower the production of reactive oxygen species in mitochondria by increasing NADH oxidation into NAD+[xxx]. A ketogenic diet promotes NAD+ levels because of fatty acid oxidation and glucose depletion[xxxi]. However, fruit can also activate enzymes that help to convert NADH into NAD+[xxxii]. So, some natural fruit can be good even on a low carb diet. Prolonged fasting suppresses mitochondrial inflammasomes by activating SIRT3-mediated superoxide dismutase 2[xxxiii]. Extended fasts for 3-5 days a few times a year are great for disease prevention and autophagy.

Extended fasts for 3-5 days a few times a year are great for disease prevention and autophagy. Reduce your stress load. Too much stress shortens telomeres but it also damages the mitochondria. That’s why a healthy lifestyle should include active stress management such as meditation and sleeping.

Too much stress shortens telomeres but it also damages the mitochondria. That’s why a healthy lifestyle should include active stress management such as meditation and sleeping. EGCG found in green tea improves mitochondrial functioning by reducing Alzheimer’s plaques[xxxiv]. You can drink it while fasting as well.

The single most effective way to promote mitochondrial function and slow down aging is to eat a diet that makes you burn more fat instead of glucose. This type of keto-adaptation increases the mitochondria’s ability to produce energy and maintain active mitophagy. High levels of glucose and carbohydrates may inhibit this process and prevent the removal of damaged particles.

If you want to learn about how to do intermittent fasting, then check out the Full Guide to Intermittent Fasting FREE BOOK!

Stay Empowered

Siim

References

[i] http://emboj.embopress.org/content/35/7/724

[ii] https://www.ncbi.nlm.nih.gov/pubmed/24304053

[iii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942780/

[iv] https://www.sciencedirect.com/science/article/pii/S0047637405001478

[v] https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30612-5

[vi] https://www.ncbi.nlm.nih.gov/pubmed/17108241

[vii] http://www.pnas.org/content/99/25/15983.full

[viii] https://www.jci.org/articles/view/97736

[ix] https://www.ncbi.nlm.nih.gov/pubmed/23140641

[x] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403509/

[xi] https://www.ncbi.nlm.nih.gov/pubmed/22395773/

[xii] https://www.ncbi.nlm.nih.gov/pubmed/22302938/

[xiii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076149/

[xiv] https://www.sciencedirect.com/science/article/pii/S0092867407009737

[xv] https://news.mit.edu/2018/study-suggests-method-boost-growth-blood-vessels-muscle-0322

[xvi] https://www.sciencedirect.com/science/article/pii/S155041311630482X

[xvii] http://science.sciencemag.org/content/355/6331/1312

[xviii] https://www.ncbi.nlm.nih.gov/pubmed/21658599/

[xix] https://www.ncbi.nlm.nih.gov/pubmed/21187328?dopt=Abstract

[xx] https://www.ncbi.nlm.nih.gov/pubmed/18371346

[xxi] https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30099-2?code=cell-site

[xxii] https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2008.164202

[xxiii] https://www.ncbi.nlm.nih.gov/pubmed/20197054/

[xxiv] https://www.ncbi.nlm.nih.gov/pubmed/19887595/

[xxv] http://jcb.rupress.org/content/199/2/205.full

[xxvi] https://www.ncbi.nlm.nih.gov/pubmed/19590001?dopt=Abstract

[xxvii] https://linkinghub.elsevier.com/retrieve/pii/S1568163714001275

[xxviii] https://www.ncbi.nlm.nih.gov/pubmed/16339438?dopt=Abstract

[xxix] https://www.ncbi.nlm.nih.gov/pubmed/18477450/

[xxx] https://www.sciencedirect.com/science/article/abs/pii/S0306452206016617

[xxxi] https://www.ncbi.nlm.nih.gov/pubmed/18477450/

[xxxii] https://joe.bioscientifica.com/view/journals/joe/208/3/273.xml

[xxxiii] http://www.jbc.org/content/292/29/12153

[xxxiv] https://content.iospress.com/articles/journal-of-alzheimers-disease/jad101629