Scientists find promising pathway that links mitochondrial damage from smoking and drinking to osteoporosis.
The risk factors of osteoporosis, an age-related disease, have long been known. But the exact mechanisms of how risk factors, like smoking and drinking, eventually contribute to accelerated bone loss has yet to form a firm picture. This may change, however, with the publishing of a study last month in FASEB Journal [1] by researchers at Penn’s School of Veterinary Medicine, which has revealed a mechanism that could become a vital clue into how the disease’s risk factors align with bone loss.
The answer, the researchers claim, lies in the mitochondria. When healthy, mitochondria are cellular organelles essential in the process of respiration (the production of cellular energy from glucose) but damage to mitochondria leads to an increase in numbers of osteoclast cells, which break down bone.
Longevity.Technology: Osteoporosis is a debilitating, life-limiting disease; tackling it on a cellular level could mean a marked improvement in the quality of life for an aging population.
The TRL score for this Longevity.Technology domain is currently set at: ‘Principles are demonstrated through experimentation.’
The TRL score for the technology addressed in this article is: ‘Principles are demonstrated through experimentation.’
“In a normal individual, the process of bone degradation and rebuilding proceeds in a very balanced way, but in some people they somehow produce a lot more osteoclasts, and this leads to bone loss and osteoporosis,” said one of the study’s senior authors Narayan Avadhani [2]. “We show in this paper that, when mitochondrial function is affected, it not only affects energy production but also triggers a type of stress signalling that induces the overproduction of osteoclasts.”
Avadhani’s lab at Penn School collaborated with the Mone Zaidi lab at Icahn School of Medicine at Mount Sinai to look deeper into mitochondrial problems affecting a specific type of immune cell called macrophages. Macrophages engulf and destroy contaminants (bacterial invaders and cellular mutineers alike) forming the immune system’s first line of response. They are also built to protect against troublesome irregularities in bone growth by transforming into osteoclasts.
The team teased out the thread leading from mitochondrial damage to macrophages and then to osteoclasts by inducing damage to cytochrome oxidase C, an important process in mitochondrial energy production. They then observed as the macrophages signalled for an inflammatory response and began on a known path to eventually becoming osteoclasts. What’s more, the team observed an irregularity with the molecule RANK-L and osteoclast levels. RANK-L is used by the body to induce bone-breakdown, but even with low RANK-L levels the team observed that the production of osteoclasts still proceeded by accelerated rates once mitochondrial damage had been induced.
“In some respects, mitochondrial stress signaling may even be replacing RANK-L,” says Avadhani [2]. “That we don’t know now, but we plan to look into that further.”
Finally, the team also observed increased rates of phagoctosis, the process by which macrophages consume and destroy invaders. They highlight this as a possible explanation for the other problems seen in those with mitochondrial defects, as well as providing a connection to risk factors like smoking, drinking and some drugs, which have been shown to cause mitochondrial damage.
All of the little that is known about mitochondrial health is confined to mouse models, so we may have to wait some years before we see effective therapies in humans. However, there are promising signs, from this report and others, of an emerging understanding becoming more visible. This is certainly a cause for some hope, and (erm) we make no bones about it.
