Inflammaging, muscle, and sarcopenia

The rhythm of muscle protein synthesis and breakdown.

As we get older, our immune systems, like other systems in aging, begin to malfunction. This is such a key component of aging that a term has been coined for it, inflammaging. This condition is characterized by increased production of inflammatory cytokines, as well as lower immune function. Cortisol is produced to counteract the inflammation, and this has deleterious consequences as well; one might compare it to driving a car while simultaneously pressing on the brakes.

In older people, sarcopenia, or the loss of muscle mass, is a major health problem, as it leads to frailty, disability, and the nursing home, from which not many people make it out alive. However, sarcopenia is really just the end result of many decades of loss of muscle mass; like other physiological systems, the deterioration of muscle mass begins much earlier, as early as the thirties and forties, such that by age 80, fully half of all muscle can be lost.

Inflammaging and sarcopenia are closely linked. The production of inflammatory cytokines results in what is known as anabolic resistance, which is the diminution or failure to respond to normal anabolic stimulus.

In all healthy people, muscle is broken down and rebuilt on a daily basis. When food is eaten, protein stimulates muscle protein synthesis; when one is in the fasted state, say overnight, muscle is broken down in order to maintain the proper level of amino acids in the bloodstream, a necessity. In healthy people these processes remain in balance, and no net muscle loss occurs. With aging, however, anabolic resistance means that this balance is disrupted, and over time, significant muscle loss occurs, with the end result of sarcopenia.

It turns out that a number of things can be done to counteract sarcopenia. A recent study found, for instance, that old rats given ibuprofen had their anabolic resistance abolished, and restored their muscle mass to levels seen in younger rats. Their levels of muscle protein synthesis rose by 25%. The authors of the study make clear the connection between inflammation and anabolic resistance, noting that “inflammatory markers and cytokines levels were significantly improved in treated old rats”.

That may all be well and good, but does this work in humans? In Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults, the researchers put older adults (mid sixties) on a resistance training program, and gave two groups of them either acetaminophen or ibuprofen. What happened next will shock you: those on the anti-inflammatory drugs gained more muscle and more strength than controls.

Over-the-counter doses of acetaminophen or ibuprofen, when consumed in combination with resistance training, do not inhibit and appear to enhance muscle hypertrophy and strength gains in older adults.

This gives convincing backing to the notion that inflammation is the cause of both anabolic resistance and sarcopenia.

Oxidative stress, or an imbalance between free radicals produced and those quenched, accompanies inflammation and is related to it. Another study done with rats found that antioxidant supplementation abolished anabolic resistance. The supplements given were rutin, vitamins E and A, zinc, and selenium.

Where does that leave us? It may not be advisable to take NSAIDs like acetaminophen or ibuprofen regularly, and in fact vitamin A and E supplementation are often not a good idea either, though specific cases could require them. More practical and safer means of overcoming anabolic resistance and avoiding sarcopenia include:

Resistance training and other forms of exercise.
Omega-3 fatty acids from fish oil. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults.
Provision of extra protein at meals. Older men who got 40 grams of protein had better muscle synthesis than those who got 20. In younger people, 20 grams of protein may suffice to promote maximal muscle synthesis; older people need more.

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Ibuprofen and Acetaminophen Enhance Exercise-Induced Muscle Strength and Size in Older Adults | Advanced Mediterranean Life says December 2, 2014

[…] h/t P.D. Mangan […]

Steve Parker, M.D. says December 2, 2014

That older adult/acetaminophen/ibuprofen study is truly amazing.

In case you’re readers are tempted to try this hack, they might want to run it by their doctors first. For instance, I wouldn’t take the acetaminophen if I had chronic liver disease. I’d eschew the ibuprofen if I had kidney impairment, were prone to bleeding, had stomach ulcers or gastritis, or were taking a strong blood thinner.

-Steve

P. D. Mangan says December 2, 2014

Thanks, Steve. Yes, fish oil and some extra protein seem a safer way to go.

jacob g. says December 3, 2014

Since the NSAIDs mentioned and fish oil are both anti-inflammatory, perhaps also supplementing with turmeric would give you the bulk of the benefits with much less risk.

Pete says December 3, 2014

Hey – found your site through your recent podcast with Jay, which was great. Your articles are informative and well written. Subscribed to your blog, and keep up the great work -Pete

P. D. Mangan says December 3, 2014

Thanks, Pete.

Sam says December 6, 2014

Wonder if aspirin would do the same? I’ve heard comments about people who before they died swelled up with a lot of water?/inflammation? I believe you also wrote about the same effect with fruit flies at your former blog.

P. D. Mangan says December 6, 2014

I think aspirin would likely work the same way.

ProudDaddy says July 29, 2015

Always ask if a given intervention works the same in the elderly. Both ibuprophen and anti-oxidants act differently in us oldies wrt hypertrophy from strength training. My guess is that interventions that bring a condition closer to healthy (young) levels can be beneficial in the elderly, even though they might be detrimental in the young. Dosage requirements can also be different even when the direction of action is the same, maybe for similar reasons.

It’s a shame that most strength training studies are done in the young.

P. D. Mangan says July 29, 2015

Yes. I believe for example that fish oil was shown to help hypertrophy only in middle-aged or older people, not in the young, so it’s essentially restoring cellular responses to a youthful level.

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Inflammaging, muscle, and sarcopenia

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