What Happens to Muscles as We Age?

Have you ever hiked up a steep path you have easily walked many times before, but had to stop and catch your breath? You sip some water, and suddenly it hits you – you’re not as young as you used to be. Your muscles ache more than they used to, and you wonder if you’re starting to feel the effects of age.

Muscle loss is a natural part of aging, and it can have serious consequences for our health and quality of life; we become more prone to falls, fractures, and other injuries that can limit our mobility and independence. In fact, without regular exercise, it’s estimated that muscle strength and mass can decline by some 10 to 15% per decade after the age of 50.^1,2,3,4

The good news is that there are research-backed actions we can take to mitigate the effects of time on our muscles. Dr. Helen Blau has devoted her career to unraveling the mysteries of muscle cell regeneration during exercise and injury, an area of research that was once shrouded in obscurity. 

Muscle stem cells play a vital role in the growth and repair of skeletal muscle tissue throughout a person’s life. Under normal circumstances, muscle stem cells are situated alongside the muscle fibers and remain inactive. However, when inflammation arises from intense exercise or injury, these muscle stem cells are triggered into action and begin repairing the microscopic damage. Many of us may be inclined to reach for an ibuprofen like Advil or Motrin to soothe the ache from the inflammation, but Dr. Blau cautions against this practice. 

According to her team’s study in mice, non-steroidal anti-inflammatory (NSAID) drugs like ibuprofen can actually hinder the body’s ability to repair damage. Specifically, these drugs reduce the activity of the signaling pathway for muscle stem cells to respond to injury damage, delaying the healing process.⁵

Skip the NSAIDs if you can avoid them. Adobe Photos

The most recent breakthrough from Dr. Blau’s lab involves muscle stem cells and the effects of aging. As we grow older, our muscle stem cells gradually lose their ability to function, meaning they don’t renew muscle tissue as well as their youthful counterparts.

“When you are younger, you can build muscle mass pretty easily,” said Dr. Blau. “After the age of 50, it’s really difficult to build muscle mass. You work hard just to maintain it.”

However, a discovery by Dr. Blau’s team may hold the key to muscle regeneration in older individuals. Her team identified a critical enzyme, which she dubbed a “gerozyme” (gero- for “old age” and -zyme for “enzyme”), that becomes more abundant as we age.⁸ The gerozyme degrades a hormone-like substance called prostaglandin-E2 (PGE2), one of the key factors in this muscle repair, reducing its abundance.⁹ The essential role of PGE2 in muscle function became profoundly clear where her team over-expressed – or artificially increased – the gerozyme in young mice for one month. There was a dramatic loss of muscle mass and muscle strength in young mice. 

Another way to think about this research is to imagine the gerozymes as unwanted guests at a construction site, making it difficult for the local workers to get their job done. When Dr. Blau increased the number of these unwanted guests, the construction site fell into greater disrepair. This gerozyme discovery is remarkable in its own right, but Dr. Blau’s work doesn’t stop there.

When Dr. Blau’s team inhibited – or decreased the activity of the gerozyme by treating the aged mice for one month with a small molecule inhibitor called SW033291 (SW), levels of PGE2 were boosted back to youthful levels. The PGE2, in turn, stimulated muscle stem cells to multiply, leading to the creation of new stem cells to replace damaged tissue. In addition, the PGE2 acted directly on mature muscle fibers, increasing energy stores, muscle mass and strength.

To return to the construction site analogy, this means Dr. Blau’s team found a way to stop the unwanted gerozymes and allow the local workers to have full access to the site again. With the gerozymes reduced, the local workers were able to repair the construction site to its former glory.   

After the age of 50, it’s more difficult to build muscle mass than when you were younger. Don’t give up! The health implications of regular exercise are still worth the extra effort. Adobe Photos

The implications of this discovery could be enormous, particularly for the millions of individuals who suffer from muscle wasting due to disuse, disease, or age-related sarcopenia. 

Dr. Blau has now founded a biotech company tasked with finding out whether or not a small molecule inhibitor similar to SW could work in humans. The goal is to test her treatment in human clinical trials and ultimately develop a drug to increase muscle strength.

“I could envision this drug treatment being useful after someone breaks a hip or they have been confined to bed, forced to be immobile and not use their muscles,” said Dr. Blau. “During that period of time, you lose your muscle mass and strength. It’s very hard to get it back, especially when you are older. So if we could help people get back on track, even with a short term treatment with this drug, I think that would be a real benefit to quality of life or healthspan, and a benefit to society in general.”