It's a sad fact that age brings diseases. Many are not life-threatening, but they still make life less fun. One of the less-fun conditions is called sarcopenia, which causes the loss of muscle mass and strength. It’s the reason why some elderly suffer from loss of stamina, difficulty in walking, and heavy breathing.
Sadly, there is no treatment for the condition—except for exercise, which only becomes more challenging because of the disease. Understanding sarcopenia, then, is crucial to developing new therapies. Recently, in a paper published in Nature, scientists described the mechanism behind this irreversible wear and tear on aging muscles.
Our body is made of trillions of cells. A tiny fraction of them—found in organs including the brain, liver, heart, gut, and blood vessels—are known as adult stem cells, which maintain and repair the organ. The resting state of these cells is "quiescent"—that is, they divide only when required for tissue repair, at which point they become active, dividing and producing the specialized cells needed for the organ they reside in.
When these adult stem cells are removed or stop functioning, the organ’s repair system stops, too. This usually happens with age, leading to degenerative diseases such as sarcopenia.
Now, researchers at Pompeu Fabra University, Bellvitge Biomedical Research Institute, and CNIC in Spain have deciphered why stem cells stop working—at least for those found in muscles. By comparing the genes that are turned "on" in muscle stem cells of mice, the researchers show that the cells of older mice undergo irreversible changes that make them exit the quiescent state, whereas younger mice avoid this change. As a result, the muscle stem cells in older mice fail to self-renew when needed. Instead, they switch to being "senescent," which leaves them unable to divide.
Normally, senescence is useful. Regardless of how old you are, millions of your body's cells become senescent every day. One of the functions of senescence is to keep a check on the uncontrolled growth of rogue cells that may become cancerous. But senescence becomes more common as we age. And in the case of the elderly, senescence among stem cells seems to bring a halt to at least one tissue repair system.
To be sure that it wasn't the environment causing this response, the researchers extracted muscle stem cells from older mice and implanted them in damaged tissue of younger mice. As expected, the geriatric cells did not repair the tissue, showing that they were committed to senescence.
But how exactly do the cells undergo these changes? The researchers found that in old muscle stem cells, there is a key gene that controls senescence: p16INK4a. This gene is overexpressed in old muscle stem cells. When p16INK4a expression was blocked, the old cells responded to tissue injury and replenished the cell population. The researchers also show that young muscle stem cells repress the production of the gene, which allows them to carry out repair work whenever needed.
The hope is that if p16INK4a can be selectively silenced, this discovery will lead to a treatment that restarts the native tissue repair system in old cells. While targeting specific genes in specific cells is not easy, keeping people younger and healthier for longer may not always be the challenge that it is now.