Arguing for Exercise to be a Useful Treatment for Sarcopenia Because it Affects Mitochondria, Unlike Most Other Attempted Interventions

In this open access paper, the authors argue that exercise (and particularly strength training) remains the best therapy for sarcopenia, the age-related loss of muscle mass and strength, because exercise improves mitochondrial function and other attempted treatments do not. This seems a reasonable position. There are many, many possible contributing causes of sarcopenia, all with accompanying evidence, but the most compelling in my opinion is stem cell dysfunction. Even so, one still needs to offer an explanation as to why exactly stem cell activity in muscle tissue declines with age, a way to link it to the root cause molecular damage of aging listed in the SENS research proposals. Perhaps faltering mitochondrial function is a noteworthy underlying cause.

Resistance exercise continues to be the most effective intervention against sarcopenia. In addition, maintenance of physical activity can delay the progression of sarcopenia. Despite the strong support for maintaining an active lifestyle, adherence to physical activity guidelines remains low. The traditional therapeutic focus of sarcopenia treatment is to target growth-related pathways to increase muscle mass. Here, we discuss the positives of these strategies, but also build a case for targeting mitochondrial bioenergetics as a way to maintain muscle mass and function with age.

The vast majority of adults fail to meet physical activity guidelines. While 60% of adults, both European and American, self-report that they meet guidelines, objectively measured physical activity reveals that fewer than 10% of adults in the United States meet physical activity guidelines. Moreover, sedentary behavior alone increases the risk for sarcopenia. While there are few trials in humans on the effects of lifelong sedentary behavior, studies in mice reveal lifelong sedentary behavior impairs mitochondrial function.

It was thought that resistance exercise training had little or no effect on mitochondrial biogenesis or function. However, recent studies have shown that resistance exercise training increases mitochondrial protein fractional synthesis rates (FSRs) and improves mitochondrial function. Young adults engaged in a resistance exercise program showed increases in mitochondrial enzyme activity and respiration. While the changes in mitochondrial respiration are modest in comparison to endurance exercise, improvements in in vivo phosphocreatine recovery rates and oxidative capacity appear comparable in older adults engaged in either exercise intervention.

Aerobic exercise is generally not appreciated as a stimulator of hypertrophy; however, there is evidence that it can lead to muscle hypertrophy. Nearly half a century ago, it was first documented that aerobic exercise increases mitochondrial content. Since then, research has consistently documented that aerobic exercise improves both mitochondrial content and function. Aerobic exercise increases mitochondrial turnover since it increases both mitochondrial biogenesis (protein synthesis) and mitophagy (mitochondrial-specific autophagy). The improvement in the rate of ATP production from aerobic exercise training suggests that more energy is available to maintain proteostasis. Additionally, improvement in mitochondrial efficiency (reduction in ROS generated per oxygen consumed or ATP generated) suggests that there is less oxidative stress and damage, which would in turn improve the quality of the proteome. In all, aerobic exercise mediated improvements in mitochondrial function likely protects against sarcopenia.

Link: https://doi.org/10.3389/fphys.2018.01883

Comments

Three related thoughts that weren't mentioned re: exercise.

1) I'm pretty convinced that exercise, resistance and aerobic, forces blood out of the marrow carrying a compliment of stem cells with it. I wish studies were done on this.

2) There is a fraction of heavier Americans who snore to the point of having trouble breathing at night. Exercise, both the positive effect on lung function and weight loss, reduces snoring. Personally, it is a guaranteed wake up call that I've slacked off if I snore even a little. Loose 5 pounds and add a day a week to my exercise routine and it disappears. (I haven't snored in almost a year now). Lower oxygen levels caused by snoring during sleep can't be healthy.

3) I know this is controversial, but there is a good hypnotic effect of the repetitive motions of running and walking (elliptical in my case). There's no money to be made studying this, so it isn't formally, but part of the "runner's high" may be attributed to this effect, and people in good mental health tend to be healthier in general. I've heard of one person who is treating PTSD with this effect.

Posted by: Tom Schaefer at February 4th, 2019 7:27 AM

I think this is relatively straight forward: subject mitochondria to the stress of mitophagy and their cells will live for longer and being able to proliferate more times (see papers on nicotinamide use in vitro). Therefore exercise is good for all cells, including stem cells/muscle satellite cells.

Posted by: Mark at February 4th, 2019 10:14 AM

Exercise, at least resistive weight training (e.g. "bodybuilding" exercise) clearly works, at least for me. I have the same physique as I did in 1988 when I started my "bodybuilding" routine. Muscle does have "memory" as well. I spent two months in Malaysia in '01 where I had no access to a gym during that time. I decided to treat it as an experiment. I was able to recover my build within 1 month of resuming training after I left Malaysia.

Of course you can find gyms everywhere these days, including Mexico and Malaysia.

Posted by: Abelard Lindsey at February 4th, 2019 10:47 AM

Re: Gyms Everywhere @Abelard Lindsey

Yes! But how to get people to use them? Jan 12 is "Quitters Day" - when half of new year's resolutioners have broken their commitments. By the size of the crowds at my awesome Planet Fitness gym, it was more like the last week in January. Last night as I was walking in, I heard a couple arguing about the 12-month automatic bank withdrawal of $10/month for a membership. I resisted the urge to tell them that just 1 avoided interaction with the medical community will pay for the membership. It could be argued that it is none of my business, but the truth is that the general morbidity statistics affect the (unbelievable) premiums the company I work for has to pay for health insurance for my family.

Posted by: Tom Schaefer at February 4th, 2019 11:16 AM

For older people NAD+ is likely to increase mitochondrial number and efficiency, and also repair and stimulate muscle stem cells, as shown in studies of old mice. It may even work people of middle age or younger who have sarcopenia problems and mitochondrial problems.

Posted by: Biotechy Marcks at February 4th, 2019 1:01 PM

Tom, I pay $53 a month for my multi-gym membership at 24 Hour Fitness. This has not gone up since '05 when I first joined this network (previously I worked out at Gold's). Its nice that there is no inflation there. I wish it was the same for other stuff I buy (like groceries for one).

People are complaining about $10 a month gym fee? Are you kidding me?

Increase morbidity is one cause of the increased health insurance premiums you and I are paying these days. I can tell you that national-socialist health care will be a lot worse, both in terms of care as well as payroll tax to pay for it.

Posted by: Abelard Lindsey at February 4th, 2019 3:48 PM

Hematopoetic stem cells do not need to be forcibly squished out of bone - and thank goodness, since that type of pressure would probably be very painful (ask a leukemia patient). HSCs are quite clever in that they can egress from bone all by themselves under the influence of chemical messengers:
https://www.ncbi.nlm.nih.gov/books/NBK27034/#_hematopoieticstemcelltrafficking_sec1-4_

Could exercise help promote physiological stem cell migration? I would not be surprised if it did, or that signal transduction of mechanostress from exercise had an influence. But I would be very surprised if the HSCs needed to be squished out.

Posted by: CD at February 4th, 2019 3:59 PM

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