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Benzoxazole May Slow Bone Ageing By 31% In Mice

Posted on 27 January 2021

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Benzoxazole is a compound with few applications by itself, but is found within the chemical structures of certain pharmaceutical drugs. It has previously been shown to extend the lifespan of C.elegans worms. Now, a longitudinal study investigating a variety of potential anti-ageing therapeutics in mice has reported that benzoxazole may slow age related bone loss.

Cartilage Is Grown in the Arthritic Joints of Mice - The New York Times
The way in which the mouse skeleton ages shares many similarities with human skeletal ageing.

Benzoxazole, the compound that slowed bone aging by up to 31% over the course of a year’s treatment in the mice, was first identified as one of five compounds that extended nematode lifespan in the Lithgow lab in a study that appeared in Nature in 2011.

“If you have a therapeutic that extends lifespan in a simple animal that has no bone whatsoever, you certainly wouldn’t predict that it would slow the rate of bone aging in a mammal,” said Gordon Lithgow, PhD, Buck professor and Vice President. “It’s obvious that aging-related pathways have been conserved during evolution. This new finding is a great example of the utility of screening compounds in simple animals as the starting point to look for unexpected and surprising benefits in mammals.”

Benzoxazole appears to reduce the activity of osteoclasts, the cells that break down bone tissue, though the mechanism by which benzoxazole has this effect is still being studied. In the original experiment in C.elegans worms, benzoxazole was found to reduce the abnormal aggregation of proteins, which is thought to be one of the fundamental drivers of ageing.

Direct conversion of fibroblasts to osteoblasts as a novel strategy for bone  regeneration in elderly individuals | Experimental & Molecular Medicine
Osteoblasts build bone tissue while osteoclasts break it down. An imbalance of these cells in old age leads to bone weakness.

The project, which involved the study of 700 ageing mice over a period of several years, also provides a database of age-related changes in mice that may help other researchers to plan their studies. As an example, it was found that 2.5% of mice experienced spontaneous femoral fractures. Researchers wishing to study an intervention for preventing age-related fractures could use this data to calculate how many mice they would need, and how long the study would need to last.

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