Ask a 70-year old weight lifter and they’ll tell you they aren’t as strong as they were when they were 30. It’s no secret that men and women lose muscle strength with age and the decline in strength mirrors loss of lean body mass, another age-related problem – but researchers have never really understood why. It’s likely that factors like an age-related drop in sex hormones, like estrogen and testosterone, and growth hormone play a role, but what’s happening at the cellular level? Recent research from McMaster University sheds new insight into why we lose strength as we age.
New Insights Into Aging Muscles and Strength
According to a new study carried out at McMaster University and published in the journal Cell Metabolism, a protein called AMP-activate protein kinase, or AMPK, may hold the key to aging muscles. In a study carried out in mice, McMaster researchers found that mice that lacked AMPK lost a disproportionate amount of muscle strength during mid-life. As the researchers pointed out, the degree of muscle loss in these middle-aged mice was what you’d expect in a mouse with a human age of 100, and the absence of AMPK seemed to fuel loss of muscle strength in these mice.
Could the same be true in humans? According to the researchers, AMPK declines in humans with age too, which may explain why humans get weaker as they get older. So powerful is AMPK in the human body that it’s sometimes referred to as a master metabolic regulator. Interestingly, AMPK is turned on when cellular energy levels drop. For this reason, it’s also called a cellular energy sensor, as it senses when fuel levels are too low and is activated in response. Once activated, it stimulates the breakdown of glycogen and fat stores to supply energy to the cells that need it.
One benefit of turning on AMPK is that it ramps up fat oxidation so that you burn more fat, and, under the right conditions, lose body fat. That’s one reason you hear fitness gurus recommending fasting cardio because hormones released in response to fasting, like adrenalin, activate AMPK. So, having souped-up production of AMPK is a plus when you’re trying to shed body fat. Of course, this means AMPK has a catabolic effect, which raises the question of why mice that lack it lose muscle strength. You would expect the opposite. In fact, research shows AMPK blocks the mTOR pathway signaling pathway that enhances muscle protein synthesis.
How AMPK, with its catabolic effects on other tissues, preserves muscle strength isn’t clear, but AMPK seems to have other benefits as well. In one study, when AMPK was turned up in fruit flies, the tiny insects lived 30% longer. In humans, researchers believe AMPK may lower the risk of metabolic problems like type 2 diabetes by improving insulin sensitivity. One way it does this is by increasing the number of receptors, called GLUT 4 receptors, on the surface of cells that can take up glucose. With more receptors available, glucose can enter cells more readily and less insulin has to be released.
Turning on AMPK
With AMPK having potential health benefits, the ability to increase fat breakdown, improve insulin sensitivity and, based on one study, preserve muscle, you might wonder how you can get the benefits. It’s easy if you’re an exercise buff because one of the strongest activators of AMPK is exercise. Muscle contraction, particularly high-intensity exercise, releases AMPK. It’s one reason why exercise is a good fat burner. Other less positive things can activate AMPK as well, including low blood sugar levels, stress, and hypoxia. When your body is low on fuel or under stress, cells build up more AMPK.
A medication used to treat type 2-diabetes and insulin resistance called metformin also increases AMPK. Interestingly, metformin, based on preliminary research may have benefits that go beyond improving insulin sensitivity. For example, some studies suggest it lowers the risk of some forms of cancer. Plus, a recent study showed it reduces the risk of glaucoma. Still, other research suggests that metformin may have anti-aging benefits. Could it be because it increases AMPK? In addition, a study published in the journal Science showed that a nonprescription medication, aspirin, turns on AMPK. One downside of high AMPK is it increases appetite, which makes sense since AMPK goes up when cells are low on fuel.
The Bottom Line
AMPK is a protein you probably don’t think much about, but it’s similar to the fuel gauge in your car, sensing when fuel is low and conveying that message to other proteins and hormones that regulate metabolism, telling them to break down glycogen and fat stores. As this new study shows, AMPK may also be instrumental in preserving strength and muscle mass as we age, although exactly how isn’t clear, especially since other studies show AMPK has a catabolic effect, turning off muscle protein synthesis, especially the synthesis of new muscle protein in fast-twitch muscle fibers. Fast-twitch fibers are the type optimized for strength and power, and the ones that decrease most with age.
Also of interest is research showing that AMPK improves metabolic health and may have longevity benefits, at least in fruit flies. AMPK may also explain some of the health benefits of exercise, including its positive effects on insulin sensitivity.
The best way to ramp up your AMPK level is with high-intensity exercise, but don’t forget about the importance of resistance training – there’s no better way to preserve lean body mass and strength as you age or to improve your body composition.
References:
Eurekalert.org. “McMaster researchers discover the key to maintaining muscle strength while we age” June 2, 2015.
J Physiol. 2006 Oct 15; 576(Pt 2): 613-624.
Daily Mail. “Scientists Say They Can Slow Aging by Activating a Gene With a ‘Remote”
Biochem J. 2009 Mar 1; 418(2): 261-275.doi: 10.1042/BJ20082055.
Medscape Family Medicine. “Exercise: How Does It Promote Insulin Sensitivity?”
Science. 2012 May 18;336(6083):918-22. doi: 10.1126/science.1215327. Epub 2012 Apr 19.
J Biol Chem (2004) 279: 12005-12008.
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