“Everybody wants to live forever but ain’t nobody want to do some heavy fasting” said someone of unknown origin. Does fasting make you live longer? Can intermittent fasting increase lifespan in humans? This article will give you some answers.

Nematode Worms and Anti-Aging

In 2017, a study published in the journal Cell Metabolism showed that aging and age-related diseases are associated with a decrease in the cells’ ability to process energy efficiently[i].

The scientists used nematode worms who live for only 2 weeks to carry out an experiment on their mitochondria, which are little organelles responsible for energy production in the cells.

They found that restricting the worms’ calories and manipulating a fuel sensor called AMPK promoted longevity by maintaining mitochondrial networks and increasing fatty acid oxidation. This happened in communication with other organelles called peroxisomes that regulate fat metabolism.

The researchers proposed that fission and fusion amongst the mitochondria’s network and fatty acid oxidation are required for the longevity benefits. For intermittent fasting-mediated lifespan increase, you need the dynamic remodeling of mitochondrial networks, which happen in response to various physiological and pathological stimuli[ii].

Caloric Restriction of Rats and Monkeys

Caloric restriction and intermittent fasting have been linked to longevity previously already.

In 1946, a study on rats found that fasting 1 day in 3 increased lifespan in males by 20% and in females by 15% [iii]. They didn’t experience any retardation of growth but what did happen was the death of tumors increased in proportion to the amount of fasting. Other studies on rodents have noted reduced inflammation and other age-related health issues[iv].

[iii]. They didn’t experience any retardation of growth but what did happen was the death of tumors increased in proportion to the amount of fasting. Other studies on rodents have noted reduced inflammation and other age-related health issues[iv]. Fasting has been shown to increase the lifespan of bacteria and yeast by more than 100% [v]

[v] Caloric restriction shows increased lifespan of brain neurons in both humans and monkeys [vi]

[vi] In 2009, a group of scientists from the University of Wisconsin reported improved biomarker and longevity benefits[vii] in rhesus monkeys who ate less. However, in 2012, a study done by the National Institute of Aging noted there to be no improvements in survival but they did find a trend toward better health.

However, in 2012, a study done by the National Institute of Aging noted there to be no improvements in survival but they did find a trend toward better health. After working through the conflicting outcomes, it’s thought that the different results were caused by several things[viii]. Caloric restriction is more beneficial in adults and older monkeys but not as so in younger animals. How much less food was eaten also affected the differences in survival rates. The monkeys in NIA ate naturally sourced foods whereas the ones in Wisconsin ate processed food with higher sugar content, which made them substantially fatter. There were also sex differences, where females seemed to have less adverse effects of obesity than males. This makes sense, as women are more prone to carrying extra fat for their offspring



Can Fasting Increase Lifespan in Humans

What about humans? Does caloric restriction and intermittent fasting have a similar effect on longevity in humans? We do share 93% of the genes with Rhesus Monkeys.

One study on 3 weeks of alternate day fasting discovered an increase in SIRT1, which is a gene associated with longevity[ix]. Sirtuin genes regulate the hypothalamus, which modulates the circadian rhythms, feeding behavior and energy expenditure[x].

Why this happens is still unclear but it’s suggested that caloric restriction induces cellular respiration, which increases NAD+ and reduces NADH levels[xi]. NADH inhibits Sir2 and SIRT1.

Sirt genes have been shown to also activate PGC-1α, which triggers the growth of new mitochondria[xii]. Sirt 3, Sirt4, and Sirt5 are also associated with improved mitochondrial function[xiii].

This may be evidence that if not increased lifespan, then caloric restriction and fasting will improve longevity of the cells. To know how it actually works, let us return to the first study we talked about on nanotode worms and their mitochondrial network dynamics.

Mitochondrial Longevity

The life cycle of mitochondria is characterized by fission and fusion events.

Fusion states happen when several mitochondria mix and organize themselves into a network

Fission states happen when the fused mitochondria get split into 2 out of which the one with a higher membrane potential will return to the fission-fusion-cycle and the one with a more depolarized membrane will stay solitary until its membrane potential recovers. If its membrane potential remains depolarized it’ll lose its ability to fuse and eventually will be eliminated by a process called mitophagy, which is the degradation of mitochondria by autophagy.

Changes in nutrient and energy availability can make the mitochondria stay in either one of these states for longer.

Post Fusion State is called Elongation, which is characteristic to states of energy efficiency, such as starvation, acute stress, caloric restriction, and senescence.

Post Fission State is called Fragmentation, which shortens the mitochondria and keeps them separate. This is typical to bioenergetic inefficiency that’s caused by high energy supply and extended exposure to excess nutrient environments.

These mechanisms show that the mitochondria evolved to adapt to drastic changes in nutrient availability in the form of fasting and feasting. 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.

How Can Caloric Restriction Increase Lifespan

All of the other genetic pathways we’ve talked about are also associated with energy efficiency and nutrient deprivation.

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. This lowers your energetic demands because the organelles in your cells are in better connection. It’ll also make you recycle old worn out cell components and convert them back into energy through the process of autophagy. Mitophagy is a layer deeper and happens inside the mitochondrial fission-fusion cycle.

Energy restriction also upregulates the other genes that increase energy efficiency by improving insulin sensitivity and fat oxidation. Remember – the increased lifespan of the nematode worms happened because of peroxisome-mediated fat metabolism.

During states of fasting or depletion of exogenous calories, your mitochondria rev up their functioning and boost endogenous energy production from internal sources.

Fasting Ketones and Penguins

Ketosis is another vital component to the survival of the mitochondria as it allows them to become more energy efficient. Fasting for 40 days in humans increases the concentration of ketone bodies and plasma free fatty acids by more than 3 orders of magnitude[xiv].

This shift of starting to burn ketones preserves muscle tissue gives adequate energy to the brain, and keeps you satiated by downregulating some of the hunger signalings.

From an evolutionary perspective, it makes perfect sense, as the mechanisms of longevity came from organisms trying to survive periods of nutrient deprivation and avoid age-related damage[xv].

In nature, there are many other species that still go through this similar process. Emperor penguins can fast for over 5 months while still living in the coldest place on earth.

Other wild animals that fast for long periods are also very efficient at sparing protein with only 2-10% of total energy coming from protein versus the 20-40% in species that are less adapted to fasting. This again shows that the longest living organisms aren’t necessarily burning off a ton of energy but are more efficient with it.

The Missing Piece of the Puzzle

However, the life-extension benefits of caloric restriction are linked to autophagy.

In one study on mice and flies, they found out that if you inhibited autophagy but still fed the animals fewer calories, they didn’t live longer, but the ones who were proficient at causing autophagy did [xvi].

This is the most important point – It means that you can still eat fewer calories, practically stay in a semi-starvation state, and not gain the longevity benefits just because you didn’t shift into a fasted state and allowed autophagy to do its work.

The mitochondrial fission-fusion cycles are also dependent on autophagy modulating pathways such as AMPK and mTOR[xvii].

mTOR or mammalian target of rapamycin is responsible for cell growth, protein synthesis, and anabolism. It promotes the activation of insulin receptors and will make the body build new tissue.

AMPK or AMP-activated protein kinase is a fuel sensor that is involved in balancing energy deprived states

mTOR inhibits autophagy because it makes your body grow, which requires conserving energy and upregulating the metabolism, whereas AMPK supports autophagy due to the energy deprived state.

Nutrient starvation allows unneeded proteins to be broken down and recycled into amino acids that are essential for survival[xviii].

Too Much Energy Leads to Inefficiencies

An additional mechanism for this is the inhibition of a hormone called IGF-1, which is associated with aging and disease.

In a study on humans, a fasting mimicking diet in diabetics reduced body fat, decreased the production of IGF-1 and lowered C-reactive protein levels, which are associated with inflammation[xix].

IGF-1 and mTOR both are elevated in the presence of an abundant supply of amino acids and glucose that inhibit the body’s ability to burn its own endogenous fat stores.

The elevation of NAD+ and Sirtuins are also linked to the mitochondria’s ability to take those stored fat slobs and burn them off for energy while giving enough energy to the brain, muscle tissue, and vital organs.

In a state of ketosis, you’re burning almost your own body fat exclusively but higher amounts of ketones in the blood aren’t indicative of good metabolic health either.

People who’ve keto-adapted after a long time tend to show lower amounts of ketones in their blood because of increased energy efficiency and utilization.

Therefore, the key to longevity and increased lifespan still gets traced back to decreased energy intake and improved energy usage within the body itself.

In Conclusion – Does Fasting Make You Live Longer

So, what to make of this? I think it’s clear that caloric restriction and intermittent fasting increase lifespan in many species and it probably has a similar effect in humans as well.

If not a direct boost in longevity, then the improvements in other biomarkers like reduced inflammation, lower body fat, and better mitochondrial function will still have an indirect effect on living longer and being more youthful.

The takeaway of this is that you should practice intermittent fasting and go through periods of caloric restriction in which you allow your body to promote its energy efficiency.

However, to prevent malnourishment and starvation, you have to actually avoid all caloric intake for a certain period of time. Keeping yourself in a constantly anabolic state whether through too frequent eating or consuming too many carbs and protein will prevent your cells from raising autophagy and can accelerate aging.

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://www.cell.com/cell-metabolism/fulltext/S1550-4131(13)00104-6

[ii] https://www.ncbi.nlm.nih.gov/pubmed/20649548

[iii] https://academic.oup.com/jn/article-abstract/31/3/363/4725632?redirectedFrom=PDF

[iv] http://stm.sciencemag.org/content/9/377/eaai8700

[v] https://www.ncbi.nlm.nih.gov/pubmed/24440038

[vi] https://www.sciencedirect.com/science/article/pii/S156816371530012X

[vii] https://www.ncbi.nlm.nih.gov/pubmed/11113597

[viii] https://www.nature.com/articles/ncomms14063

[ix] https://www.ncbi.nlm.nih.gov/pubmed/15833943

[x] http://genesdev.cshlp.org/content/27/19/2072?top=1

[xi] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627124/

[xii] https://www.ncbi.nlm.nih.gov/pubmed/15716268 / https://www.ncbi.nlm.nih.gov/pubmed/15744310 /

[xiii] https://www.ncbi.nlm.nih.gov/pubmed/23209156

[xiv] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946160/figure/F3/

[xv] https://www.ncbi.nlm.nih.gov/pubmed/24440038

[xvi] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032517/

[xvii] C. A. Lamb, T. Yoshimori, and S. A. Tooze, ‘The Autophagosome: Origins Unknown, Biogenesis Complex’, Nat Rev Mol Cell Biol, 14 (2013), 759-74 / R. C. Russell, H. X. Yuan, and K. L. Guan, ‘Autophagy Regulation by Nutrient Signaling’, Cell Res, 24 (2014), 42-57

[xviii] http://ec.asm.org/content/1/1/11.long / http://science.sciencemag.org/content/290/5497/1717

[xix] http://www.cell.com/cell/fulltext/S0092-8674(17)30130-7