Identifying Age-Related Epigenetic Changes Related to Reduced Function in Mesenchymal Stem Cells

Stem cells maintain tissue by providing a supply of daughter somatic cells to replace losses. This stem cell activity declines with age, and a sizable fraction of that decline in the most studied populations appears to be a reaction to the aged signaling environment rather than intrinsic dysfunction, at least in earlier old age. The behavior of cells lacking damage is controlled by their epigenetic state, alterations to the genomic machinery that governs the production of specific proteins. Could long term health be significantly improved by altering the epigenetic state of old stem cells, overriding their reaction to the aged tissue environment, and maintaining function at youthful levels? The consensus view of stem cell aging is that loss of function is an evolved response that serves to minimize cancer risk, but equally the evidence to date from animal studies suggests that there is considerable room to improve stem cell function and tissue maintenance in later life without greatly raising cancer risk.

Researchers have been looking at epigenetics as a cause of ageing processes for some time. Epigenetics looks at changes in genetic information and chromosomes that do not alter the sequence of the genes themselves, but do affect their activity. One possibility is changes in proteins called histones, which package the DNA in our cells and thus control access to DNA. A research group has now studied the epigenome of mesenchymal stem cells. These stem cells are found in bone marrow and can give rise to different types of cells such as cartilage, bone, and fat cells.

"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 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."

The researchers then investigated whether the epigenome of stem cells could be rejuvenated. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate. The cell converts the acetate into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. The treatment caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells. To clarify whether this change in the epigenome could also be the cause of the increased risk in old age for bone fractures or osteoporosis in humans, the researchers studied human mesenchymal stem cells from patients after hip surgery. The cells from elderly patients who also suffered from osteoporosis showed the same epigenetic changes as previously observed in the mice.


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