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BLOG: March 2020

Help your mitochondria slow down aging

Some may find it odd, but at this point of our civilization, as we are thinking we might be grasping what the beginning of Time looked like, we're still not sure why do we age and die.

For a few decades now, seems that ageing has much to do with mitochondria - the energy producing organelles of every cell - losing control over its ROS production.

ROS, or reactive oxygen species, are the most relevant form of free radicals for biological systems. They are oxygen based, i.e. either oxygen atoms, or molecules containing oxygen atom with unpaired electron(s) in their outer orbit (since oxygen atom has two unpaired electrons in its outer shell). That makes them unstable, highly reactive with other molecules - cellular proteins, lipids, or even mDNA (mitochondrial DNA) -  which consequently can get chemically changed(oxidized), i.e. damaged.

ROS produced by mitochondria, like superoxide anion, hydroxyl radical,
and hydrogen peroxide, however, are also necessary for cellular functions. They have important role in intracellular signaling and regulation, ensuring coordinated function of mitochondria with the rest of the cell. So, too low ROS levels will compromise cellular function, with mitochondria supplying rest of the cell with needed energy.

On the other hand, excessive ROS level, if left unchecked, will induce sustained damage to cell's mitochondria, activating mechanisms leading to programmed cell's death, apoptosis. But,

the damage can be significant much before that happens.

Keep in mind that all cellular processes need energy supplied by mitochondria. If they are compromised, so are all cellular functions, from assimilation to detox and repair.

So, in order for the cell to function properly - or even survive - it has to be able to keep its ROS level in balance with its need for them. As an important part of it, the cell produces and uses powerful intracellular antioxidants-enzimes, like superoxide dismutase (SOD), catalase, glutathione peroxidase, and others. It also have mechanisms to decrease ROS emission, for instance though ADP (adenosine di-phosphate) action.

As we age, this protective action becomes less efficient. Intracellular ROS level steadily raises, primarily damaging their main source, mitochondria. As a result,

the cells are becoming increasingly less viable, more cells die without being replaced, and the body becomes less and less functional.

Body tissues literally shrink. Ageing of skeletal muscles, or sarcopenia, results in the reduction of body's muscle mass, and similarly shrink, in general, all other tissues. Mitochondria themselves diminishes, both, in number and size.

Physical activity

Is there a way to influence this age-related mitochondrial dysfunction in keeping its ROS level in balance? As the evidence from studies on both, people and rodents, points out, those aged and physically active have significantly:

more muscle mass

higher protein synthesis

higher mitochondrial efficiency (biogenesis)

higher antioxidant activity

higher ability to reduce ROS emission

than the aged physically inactive.

Higher mitochondrial biogenesis means mitochondria are effectively younger, and so are us. The last two effects imply lower oxidative stress on mitochondria, the direct cause of mitochondrial deterioration and ageing resulting from it.

Most people, particularly in urban areas, have insufficient level of physical activity, unless it's achieved through practicing regular exercise. While any form of exercise will do - endurance, resistance or, better than either alone, both combined -

the accent is on *regular*

(other modalities, like high-intensity interval training, organic exercise, or pretty much any regular physical activity, should be beneficial as well).

Aerobic exercise, for instance, is cited as having direct beneficial (stimulating) effect on genes regulating mitochondrial function. On the other side, resistance training is best for preserving - or even adding - muscle mass.

While there seem to be no age limit for generally healthy individuals with respect to the form of exercise - Brunetta et al. cite in their study case of a 90-year+ women, who gained muscle mass and strength through heavy resistance exercise training -

it is recommended to start slowly, for those who didn't exercise regularly, and never push much beyond the comfort level.

Proper diet

Another way to keep your mitochondria - and yourself - young, is through proper diet. Since oxidative damage generally causes inflammation, antioxidants in general will be beneficial. But for the mitochondria, and the entire cellular interior, most important are the above mentioned cellular antioxidant-enzymes. And for efficient function they need minerals.

The key cellular antioxidants, superoxide dismutase (SOD), for instance, has two varieties: the one predominantly active in the mitochondrion uses manganese, while the other, found in the cellular fluid (cytosol) contains copper and zinc.

Catalase is an iron-containing enzyme, helping neutralize hydrogen peroxide, although it is less important than selenium-containing glutathione peroxidase.

The tricky part with minerals is that the standard plasma test is highly unreliable, due to maintaining plasma mineral level being body's priority. In other words, plasma level of any specific mineral can be within normal, while rest of the body

can be literally starving for it.

Best protection, as always, is eating variety of foods, as unprocessed as possible, and take a good broad-spectrum nutritional supplement - preferably switching from one to another.

It is probably no surprise that Omega-3 fatty acids are also cited as being beneficial to mitochondria. A 6-month supplementation slowed down muscle mass and strength loss in older subjects. Their action is also associated with stimulating genes regulating mitochondrial function.

Another group of nutrients that can help your mitochondria are plant polyphenols, widely present in unprocessed foods (the most significant group are flavonoids). Closely related to them is resveratrol.

There is a number of supplements that help mitochondria stay well and alive, from Nicotinamide Riboside and PQQ, to glutathione and CoQ10. Some of them may stimulate new mitochondria growth. But so could sunshine, or short exposures to cold.

This is, of course, only the tip of the iceberg of all the complexity of mitochondrial function, and its role in ageing. But it does make a more compelling case for sticking to the two well established healthy lifestyle rules: healthy diet and regular physical activity (add good night's sleep and low stress level to complete the big picture).

It is not only about staying healthy, it is also about aging slower - that is, staying as much younger.

1. Mitochondrial ROS and Aging: Understanding Exercise as a Preventive Tool, Brunetta et al. 2019
2. Oxidative Stress, Mitochondrial Dysfunction, and Aging, Cui et al. 2011
3. Mitochondria-Ros Crosstalk in the Control of Cell Death and Aging,
Marchi et al. 2011



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