August 17, 2022

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The humble acetate rejuvenates aging mesenchymal stem cells

The humble acetate rejuvenates aging mesenchymal stem cells



 

Nature Aging: The humble acetate rejuvenates aging mesenchymal stem cells.


As we age, our bones become thinner, we suffer fractures more frequently, and bone diseases like osteoporosis are more likely to occur.

 

Now, in a new study, researchers from the Max Planck Institute for the Biology of Aging and the University of Cologne in Germany have found that the reduced function of mesenchymal stem cells after aging is due to changes in their epigenome.

They were able to reverse these changes in isolated mesenchymal stem cells by adding acetate.

This epigenomic fountain of youth could be an important treatment for bone diseases such as osteoporosis. The relevant research results will be published in the journal Nature Aging in September 2021 .

 

The humble acetate rejuvenates aging mesenchymal stem cells

 

Scientists studying aging have cited epigenetics as the cause of the aging process for some time. Epigenetics studies changes in genetic information and chromosomes that do not alter the sequence of the gene itself, but do affect its activity.

One possibility is changes in the histone proteins that package DNA in our cells and thus control access to DNA.

Corresponding author Peter Tessarz of the Max Planck Institute for the Biology of Aging and his team have now investigated the epigenome of mesenchymal stem cells.

These stem cells are found in the bone marrow and can give rise to different types of cells, such as chondrocytes, bone cells and fat cells.

 

 

Epigenetic changes in aging mesenchymal stem cells

“We wondered why as we age, these stem cells produce less and less substances for bone development and maintenance, resulting in More and more fat accumulates in the bone marrow. To do this, we compared the epigenome of mesenchymal stem cells in young and old mice. We can see that the epigenome of these stem cells increases with age There are marked changes in growth. Genes that are important for bone production are particularly affected.”

 

 

Mesenchymal stem cell epigenome restores youth

The authors then investigated whether the epigenome of mesenchymal stem cells could restore youth.

To do this, they treated mesenchymal stem cells isolated from mouse bone marrow with a nutrient solution containing sodium acetate.

These stem cells convert sodium acetate into a building block that enzymes can attach to histone proteins to increase access to genes and thus their activity.

“This treatment impressively caused epigenome rejuvenation of these stem cells, improved the activity of these stem cells, and resulted in increased production of bone cells,” Pouikli said.

 

The humble acetate rejuvenates aging mesenchymal stem cellsChromatin compaction and histone hypoacetylation in aging mesenchymal stem cells. Image from Nature Aging, 2021, doi:10.1038/s43587-021-00105-8.

 

To elucidate whether such epigenomic changes may also be responsible for the increased risk of fractures or osteoporosis in humans in old age, the authors studied human mesenchymal stem cells from patients following hip surgery. Mese

nchymal stem cells from elderly patients who also had osteoporosis showed the same epigenetic changes previously observed in mice.

 

 

 

A new treatment for osteoporosis ?

Tessarz explained, “Sodium acetate is also available as a food additive, however, its use in this form is not recommended to combat osteoporosis because the effects we observed are very specific to certain cells. However, there have been Preliminary experience with stem cells for osteoporosis. Treatment with acetate may also work in this case. However, we still need to investigate the effects on the whole organism in more detail to rule out possible risks and side effects. “

 

 

 

 

 

Reference:
Andromachi Pouikli et al. Chromatin remodeling due to degradation of citrate carrier impairs osteogenesis of aged mesenchymal stem cells. Nature Aging, 2021, doi:10.1038/s43587-021-00105-8.
Carina Groh et al. Mitochondrial carriers set the epigenetic age. Nature Aging, 2021, doi:10.1038/s43587-021-00111-w.

The humble acetate rejuvenates aging mesenchymal stem cells

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