Scientists looking into the biological mechanisms behind deteriorating bones have made a discovery that could help tackle age-related conditions like osteoporosis, by rejuvenating stem cells that are central to the process. The newly published study demonstrates how certain changes compromise the performance of these stem cells as they age, but also shows how sodium acetate can be used to reinstate their ability to drive the development of new bone material.
It is a natural function of aging that parts of the human body don't work as well as they used to, and the same is true of the mesenchymal stem cells in our bone marrow. Like other stem cells, these cells have the ability to differentiate into other cell types to form new tissue or other biological material, and in this context they are central to the generation of cartilage, bone and fat cells. Their capacity to do so, however, deteriorates as we grow older.
Scientists at the Max Planck Institute for Biology of Ageing and the University of Cologne sought to dig into the reasons why, and this led them to what is known as epigenetics. This field of science centers on the way external environmental factors can influence the activity of our genes and the way our body responds to them, without altering the sequence of the genes themselves.
We've seen some interesting research around how epigenetic changes that occur with age might shape certain health outcomes. This includes a 2017 study that showed how low-calorie diets can slow down a type of epigenetic change called DNA methylation, a chemical activity that controls when a gene should or shouldn't be expressed, leading to a longer lifespan.
The new study focuses on another type of epigenetic change known as histone modification. Histones are proteins that help package up the DNA in our cells and control access to it, and by studying how they evolve in relation to mesenchymal stem cells, the authors may have found a way to regulate the process.
"We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow," explains Andromachi Pouikli, first author of the study. "To do this, we compared the epigenome of stem cells from young and old mice. We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected."
To explore how they might be able to turn back the clock on these aging cells, the team isolated them from the bone marrow of mice and treated with them with a nutrient solution containing sodium acetate, a common food additive. This treatment converted the acetate into a building block that enzymes then attached to histones, which increased access to the genes and boosted their activity.
"This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells," Pouikli says.
The team then looked at this process in humans, studying mesenchymal stem cells taken from patients undergoing hip surgery. The cells harvested from elderly patients suffering from osteoporosis, a disease in which bones become thin and fragile, exhibited the same epigenetic changes observed in the mice. There are still questions to answer around the safety of sodium acetate use in therapies for these types of conditions, but these early results are promising.
"Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells," says Peter Tessarz, who led the study. "However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects."
The research was published in the journal Nature Aging.
