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Age or Inflammation? Both.

Posted on March 28, 2019

For years, researchers have known that injured bones do not heal as quickly in the elderly as they do in younger people. This has long been chalked up to the aging process, but a new study published in the Proceedings of the National Academy of Sciences (PNAS) says it’s not age – it’s inflammation.

The results of the study show that while the breakdown of protein-producing cells and large molecules develops over time, the remnants of this breakdown trigger an immune system response.

The immune system plays an essential role in protecting health; it recognizes and destroys germs and other microbes that can cause illness.

While this role is critical to staying healthy, the immune system can malfunction at times. It can react to proteins native to the body and increase inflammation.

Inflammation is the body’s weapon against foreign microbes and facilitates the beginning of the healing process.

But, according to the PNAS study, inflammation can also slow down healing by blocking signals to stem cells involved in the bone repair process.

When this happens, a smaller number of stem cells are available to start regenerating new bone after a break. This means that fractures do not heal as quickly, and new bone tissue is weaker after the break.

To stop the inflammation from interfering with healing, the researchers on the study treated aging mice with an anti-inflammatory ingredient found in aspirin.

After treatment, the mice showed an increase in the number of skeletal stem cells in the fracture site and the cells were readily producing new bone cells.

This evidence supports the notion that age-associated inflammation, called “inflamm-aging” by the study authors, is the reason behind the decline in the number of skeletal stem cells and their dysfunction after a fracture.

The Impact of an Injury

According to statistics, more than three out of every five injuries are to the musculoskeletal system. This, in conjunction with a high occurrence of diseases that weaken the skeletal system, makes understanding bone fractures and developing new ways to heal them a priority.

“Although bone fractures are seldom fatal, they still can negatively impact an individual’s quality of life,” said Dr. Joel Singer, a New York personal cell physician.

Bone fractures can be more severe in the elderly, and in some cases, they may never heal at all.

It’s Not the Years

During the study, the researchers observed in human patients a decline in the number of skeletal stem cells in the bone marrow as people age. When stem cells decrease, fractures take longer to heal.

After their observation in human patients, the researchers moved to mouse models to explore why this decrease happens in the first place.

While working with the mice, the study authors found that by exposing stem cells taken from young mice to the blood serum of older mice, the rate in which the skeletal stem cells multiplied was significantly reduced. The cells were put into an irreversible state known as senescence, a condition in which cells stop dividing.

Adding to the problem is the evidence determined from previous studies that shows cells in senescence send signals to the body to increase inflammation.

“When the body increases inflammation and keeps it going for long periods, some unwanted side effects occur,” Singer said.

These effects include joint pain, damage to organs and tissues, and the potential for developing autoimmune conditions.

The researchers noted that after exposing stem cells taken from young mice to blood serum of older mice turned on an immune system protein known as NF?B. NF?B works with a cell’s DNA to activate the pro-inflammatory genes that cause skeletal stem cells to stop regenerating.

To block NF?B from activating the immune system response and increasing inflammation, researchers used sodium salicylate, a component found in aspirin. The result yielded changes in cell DNA to resemble that of young skeletal stem cells.

The researchers hope their study can lead to new treatments of fractures and prevention of future fractures, as they believe the use of sodium salicylate could help some individuals to build up a “bank” of skeletal stem cells ready to go to work when an injury occurs.

Source: NYU Langone Health / NYU School of Medicine. “‘Inflamm-aging’ causes loss of bone healing ability in the elderly.” ScienceDaily. ScienceDaily, 18 March 2019.

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