The mechanism responsible for changes in bone function during ageing has been found to be hidden within the epigenome, opening possibilities for bone rejuvenation and treatment.
As we age, our bones become thinner, bringing a greater risk of bone fractures and diseases such as osteoporosis. However, a recent study, published in Nature Ageing, has proposed that the reason for this is due to changes in the epigenome, specifically in mesenchymal stem cells, which are found in bone marrow and make many different types of cells such as cartilage, bone and fat.
Andromachi Pouikli, first author of the study, explained that '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.'
To identify how the stem cell epigenome had changed over time, researchers from the Max Planck Institute for Biology of Ageing in Cologne, Germany and the University of Cologne compared the epigenome in bones from young and old mice.
The researchers found that key epigenetic differences were due to a protein family called histones, and the chemical modifications associated with them. Histones are able to modulate how accessible the DNA is, and thereby can regulate whether certain genes are able to become active or silent. Over time, a histone modification called acetylation was reduced in the stem cells as its mitochondrial carriers degraded, lowering the activity of bone-forming genes.
To determine whether the epigenetic ageing process was reversible, mouse mesenchymal stem cells were treated with a solution containing the nutrient sodium acetate. The stem cells were able to use the sodium acetate for histone acetylation, which resulted in the DNA becoming more accessible. This led to a rejuvenation of the expression of genes involved in bone marrow integrity and the production of bone cells.
The researchers went on to study human mesenchymal stem cells from patients with osteoporosis and discovered that the human cells showed the same epigenetic changes that were seen in the mice, leading to the belief that stem cell therapies could be developed to treat osteoporosis.
However, corresponding author Dr Peter Tessarz warned: '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... We still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects.'