The Importance of Mitochondrial Biogenesis
Healthy mitochondria are at the core of staying healthy and preventing disease. Mitochondrial damage can trigger genetic mutations that can contribute to cancer, so optimizing the health of your mitochondria is a key component of cancer prevention. Autophagy is one way to remove damaged mitochondria, but biogenesis is the process by which new healthy mitochondria can be duplicated.
Interestingly, exercise plays a dual role as it not only stimulates autophagy but is also one of the most potent stimulators of mitochondrial biogenesis. It does this by increasing a signal in your body called AMPK, which in turn activates PGC-1 alpha.
By stimulating your mitochondria — the organelles in nearly every cell that produce ATP — to work harder, your mitochondria start making reactive oxygen species (ROS), which act as signaling molecules. One of the functions they signal is to make more mitochondria.
In essence, the key to preventing disease — virtually eliminating the risk of cancer, heart disease, diabetes, many other diseases — and slowing down the aging process lies in optimizing mitochondrial function and increasing mitochondrial numbers. Thankfully, exercise helps you do both.
Intermittent Fasting — Another Way to Boost Autophagy
Fasting is another biological stressor that produces many beneficial results, including autophagy. In fact, some of the benefits associated with fasting — such as a reduced risk of diabetes and heart disease — can at least in part be attributed to this process.
While there are many different kinds of intermittent fasting schedules, if you’re insulin resistant, my personal recommendation is to fast every day by scheduling all of your eating within a window of approximately 8 hours or less. For example, you could restrict your eating to the hours of 11am and 7pm. This equates to 16 hours of daily fasting.
I used to recommend skipping breakfast, but I’ve since realized that it probably doesn’t matter which meal you skip — breakfast or dinner — as long as you skip one of them. Some really struggle without breakfast, so play around with it and find out what works best for you.
Eating between the hours of 8 a.m. and 4 p.m. may work better for some people, and this schedule actually has an added advantage, because you’re now fasting for several hours before going to bed. I’m convinced that it’s best for most to avoid eating three hours prior to bed, as the last thing you need to be doing is producing energy when you don’t need it.
There’s compelling evidence showing that when you supply fuel to your mitochondria at a time when they don’t need it, they leak a large number of electrons that liberate reactive oxygen species as free radicals.
These free radicals damage your mitochondrial and eventually nuclear DNA. There’s also evidence indicating that cancer cells uniformly have damaged mitochondria, so eating too close to bedtime is not a good idea. I personally strive for six hours of fasting before bedtime, but at bare minimum, avoid eating at least three hours before going to bed.
To Boost Autophagy, Switch to a High-Fat, Low-Carb Diet
Nutritional ketogenesis is a third strategy that will help boost autophagy, and to accomplish that, you need to cut down on the non-fiber carbs and increase the amount of healthy fat in your diet, along with a moderate amount of protein. (Many Americans tend to eat far more protein than they need, which will counteract your efforts to get into nutritional ketosis.) According to Champ:3
“Ketogenesis is like an autophagy hack. You get a lot of the same metabolic changes and benefits of fasting without actually fasting ... Between 60 and 70 percent of one’s overall calories should come from [healthy] fat ... Protein makes up 20 to 30 percent of calories, while carbs are kept below 50 grams per day ... Similar benefits have been noted in people following a diet in which carbs didn’t exceed 30 percent of their overall calories.”
Most Americans consume harmful fats like processed vegetable oils, which will invariably make your health worse. Not only is it processed, it’s very high in omega-6 oils, and excess omega-6 fats will integrate into the inner mitochondrial membrane and become highly susceptible to oxidative damage, causing your mitochondria to die prematurely.
It is best to keep omega-6 fats consumption to less than 4 to 5 percent of your total daily calories. Replace the omega-6 fats with healthy fats- such as natural, unprocessed fat- found in real foods such as seeds, nuts, real butter, olives, avocado, or coconut oil.
It’s also important to make the distinction about which carbs we're talking about when we say “low-carb,” as vegetables are "carbs" too. However, fiber carbs (i.e. vegetables) will not push your metabolism in the wrong direction — only the non-fiber ones will (think sugars and anything that converts to sugar, such as soda, processed grains, pasta, bread and cookies, for example).
Even more importantly, the fiber is not broken down by sugar but travels down the digestion system, is consumed by bacteria in your intestine, and converted to short chain fats that actually improve your health.
If you look at the nutrition facts on a processed food package, it will list total carbs, and again, that's not what we're talking about. To calculate the dangerous non-fiber carbs, simply subtract the grams of fiber from the grams of total carbohydrate in the food in question. Remember, you do need carbs, but you need most all of them from vegetables, which are also high in fiber.
Autophagy Restores Function in Aging Muscle Stem Cells
It has long been known that mesenchymal stem cells (MSCs) in skeletal muscle are an important part of the muscle repair process. Previous research4 has shown that exercise affects the behavior of your muscle stem cells, and may help prevent or even restore age-related muscle loss. MSCs in muscle are very responsive to mechanical strain, and these stem cells accumulate in muscle post-exercise.
And, while the MSCs do not directly contribute to building new muscle fibers, they do release growth factors, which encourage other cells to generate new muscle. It’s also known that people's muscles tend to become increasingly deficient in MSCs with age, and that autophagy efficiency declines as well. As a result, metabolic waste starts to build up in your cells and tissues.
A recent Spanish study5 reports that satellite cells — muscle stem cells responsible for tissue regeneration — rely on autophagy to prevent the arrest of the cell cycle, known as cellular senescence; a state in which stem cell activity significantly declines. In short, to improve the regeneration of muscle tissue, you need to augment autophagy.
With efficient autophagy — your body’s internal cleaning mechanism — your stem cells retain the ability to maintain and repair your tissues.
As reported by Fight Aging:6
“The researchers demonstrated that restoring youthful levels of autophagy in old satellite cell populations can restore them from senescence and return their regenerative capabilities ... The paper ... is one of the more compelling of recent arguments for putting more effort into treatments based on artificially increased levels of autophagy ...
[M]any of the methods known to modestly slow aging in laboratory species are associated with increased levels of autophagy. It is a vital component in hormesis, wherein causing a little damage leads to a lasting increase in autophagy and a net gain. Stem cells spend much of their time in a state of quiescence, only springing into action when called upon.
This helps to preserve them for the long term. In older tissues with greater levels of molecular damage, ever more stem cells slip from quiescence into an irreversible senescent state. These senescent cells are no longer capable of generating new cells, and start to secrete all sorts of harmful signal molecules.”
Health and Longevity Are Rooted in Mitochondrial Function
The take-home message here is that your lifestyle determines your fate in terms of how long you’ll live and, ultimately, how healthy those years will be. For optimal health and disease prevention, you need healthy mitochondria and efficient autophagy (cellular cleaning and recycling), and three key lifestyle factors that have a beneficial effect on both are:
1. What you eat: A diet high in quality fats, moderate in protein, and low in non-fiber carbs. Eating organic and grass-fed is also important, as commonly used pesticides like glyphosate cause mitochondrial damage
2. When you eat: Daily intermittent fasting tends to be the easiest to adhere to, but any fasting schedule that you will consistently follow will work
3. Exercise, with high intensity interval exercises being the most effective.
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Sources and References:
Mercola, J. (2016). “Autophagy — How Your Body Detoxifies and Repairs Itself.” Mercola.com. Joseph Mercola, published 11 March 2016. Accessed 23 August 2016.
Image Credit: Racoma, I.O.; Meisen, W.H.; Wang, Q.E.; Kaur, B.; Wani, A.A. PLoS ONE. “Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase-independent cell death in glioblastoma cells.”
<https://openi.nlm.nih.gov/detailedresult.php?img=PMC3767730_pone.0072882.g006&req=4>. Published 2013. Accessed 28 August 2016.
2, 5, 6. Fightaging.org January 7, 2016
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