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Arthur T Knackerbracket writes:

Unlocking the mystery behind skeletal aging:

Researchers from the UCLA School of Dentistry have identified the role a critical enzyme plays in skeletal aging and bone loss, putting them one step closer to understanding the complex biological mechanisms that lead to osteoporosis, the bone disease that afflicts some 200 million people worldwide.

The findings from their study in mice, published online today in the journal Cell Stem Cell, could hold an important key to developing more effective treatments for osteoporosis and improving the lives of an aging population, they say.

Cells in the bone marrow known as mesenchymal stem cells serve as the building blocks of the body's skeletal tissues, but whether these stem cells ultimately develop into bone or fat tissues is controlled in part by what are known as epigenetic factors — molecules that regulate genes, silencing some and activating others.

[...] In one important scenario, the scientists examined stem cell senescence, or deterioration and exhaustion — the natural process by which mesenchymal stem cells stop rejuvenating or creating more of themselves over time. The team unexpectedly found that senescence, which leads to natural skeletal aging, was characterized by a loss of KDM4B.

[...] Finally, the team showed that parathyroid hormone, an anabolic drug approved by the U.S. Food and Drug Administration for the treatment of aging-related bone loss, helps to maintain the pool of mesenchymal stem cells in aging mice in a KDM4B-dependent manner.

The results not only confirm the critical role KDM4B plays in mesenchymal stem cell fate decision, skeletal aging and osteoporosis, but they show that the loss of KDM4B exacerbates bone loss under a number of conditions and, surprisingly, that KDM4B controls the ability of mesenchymal stem cells to self-renew. This study is the first in vivo research to demonstrate that the loss of an epigenetic factor promotes adult stem cell deterioration and exhaustion in skeletal aging.

Entry for KDM4B on Wikipedia.

Journal Reference:
Peng Deng, Quan Yuan, Yingduan Cheng, et al. Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging. Cell Stem Cell, 2021; DOI: 10.1016/j.stem.2021.01.010

Original Submission