With age, the form and function of our bones and muscles drop off, putting us as increased risk for frailty and falls.

Now researchers at the Medical College of Georgia at Augusta University are dissecting just what happens to the stem cells that make the tissues, which help keep us upright, with an eye on improving our healthspan.

“After age 65 you start losing about 1 percent of both muscle and bone per year,” said Dr. Carlos Isales, endocrinologist, Regents’ professor and vice chair for clinical affairs in the MCG Department of Neuroscience and Regenerative Medicine.

Time seems to alter the dynamic between the mesenchymal stem cells making bone and muscle and the amino acids that fuel them. The MCG scientists also have evidence it changes the signals stem cells send each other.

The bottom line: Our stem cell population gets reduced and the cells we have become less efficient at making bone and muscle, often opting for the easier task of making fat instead, Isales said.

The team, which includes principal investigators bone biologist Dr. Mark Hamrick, stem cell researcher Dr. William D. Hill and biomedical engineer Dr. Meghan McGee–Lawrence, wants to keep stem cells focused on making bone and muscle.

Much as the function of bone and muscle is interwoven, so is their health and the factors that promote their loss or survival also are similar, said Hamrick.

A major culprit in their breakdown appears to be the metabolite kynurenine, a byproduct of the essential amino acid tryptophan. Tryptophan is among the nine amino acids our body can’t make and we must consume in foods like turkey and soybeans so we can perform essentials like making protein. The researchers also think the fuel sends signals to cells, ones that aging stem cells apparently don’t get.

The unhealthy metabolite is the result of a natural action called oxidation, which occurs anytime cells use oxygen. Particularly with age, the free radicals produced by oxidation can also damage cells. Kynurenine results when the enzyme, indoleamine 2,3 dioxygenase, or IDO, which a variety of tissues make to help moderate an immune response, oxidizes tryptophan. Over time, kynurenine piles up and appears to alter the dynamic of bone and muscle formation.

Again, somewhat ironically, the many functions of essential amino acids include working as antioxidants, so the researchers are putting together nutrient cocktails – minus tryptophan and with reduced protein content – that they hope can reverse age–related damage. Isales notes that they may find that other amino acids produce similar problems as tryptophan in the aged environment.

So they also are taking more direct approaches like whether an IDO inhibitor – which is already in clinical trials as a cancer fighter – can reverse changes and get stem cells to regain more youthful function.

They have laboratory evidence that in mice at least, high kynurenine levels impact the ability of cells in the bone marrow to make bone–forming cells called osteoblasts. In fact, even relatively young mice fed kynurenine experience bone loss, an increase in bone destruction by cells called osteoclasts and increased fat in their bone marrow. Conversely, mice with IDO knocked out maintain strong bone mass.

The team also has evidence that part of how age–related increases in kynurenine does damage is by altering microRNAs – small but powerful pieces of RNA that can control expression of hundreds of genes at the same time – as well as vesicles called exosomes that are hauling the microRNAs around. Stem cells secrete exosomes as one way to communicate, and apparently aging stem cells don’t communicate well with each other.