Irisin Links Exercise and Bone Strength

Researchers here find that the beneficial effects of regular exercise on bone density and strength are mediated in part by irisin, which acts on a receptor found on the surface of osteocytes. Osteocytes are a class of cell responsible for the constant remodeling of bone tissue that takes place throughout life, alongside osteoclasts and osteoblasts. The loss of density and strength in bone that occurs in later life, known as osteoporosis, is an imbalance between creation and destruction of bone. It might be reduced by means of modifying the behavior of the cells responsible for these activities, though to my eyes it would be preferable to identify the forms of underlying damage in aging that lead to this imbalance and then work to repair them.

Researchers have proposed that the irisin hormone serves as a link between exercise and its beneficial effects on health, including burning fat, strengthening bones, and protecting against neurodegenerative diseases. Until now, however, researchers hadn't identified a specific molecular receptor for irisin - in effect, a docking structure allowing irisin to bind to cells and tissues. They are now reporting that the irisin receptor is a group of proteins called integrins situated on the surface of osteocytes.

Osteocytes are cells that act as the "command and control unit" for bone remodeling - that is, the loss and replenishment of bone that occurs both normally and in pathological states. Some research previously found that intermittent injections of irisin increased bone density and strength in mice. Now that it has shown that irisin targets the osteocyte through a specific receptor, the irisin-bone connection can be explored more mechanistically.

Osteocytes gradually die off with age, and their loss is believed to be a cause of age-related osteoporosis, the thinning and weakening of bones. In cell culture, the scientists observed that treating osteocytes with irisin protected them from being killed by hydrogen peroxide - a simulation of age-related death. The experiments also showed that treating osteocytes with irisin increased their production of sclerostin, a protein that triggers bone remodeling, and injecting irisin into mice raised their sclerostin levels. Sclerostin actually triggers the breakdown of bone, which might seem harmful rather than helpful. However, the intermittent breakdown of bone seems to be interpreted as a signal to remodel and build bones. So how could manipulating irisin be used therapeutically? Some form of intermittent irisin treatment might work.



FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

"Irisin might play an important role in reducing the risk of obesity, insulin resistance, or several related diseases, and high irisin levels may contribute to successful aging. Thus, the irisin precursor (FNDC5) gene is a candidate to influence exceptional longevity (EL), i.e., being a centenarian."

Fructose consumption reduces Irisin levels.

"Our results show that fructose ingestion impairs the expression of genes involved in biological processes relevant to exercise-induced remodeling of skeletal muscle. This might provide novel insight on how a dietary factor contributes to the genesis of disorders of glucose metabolism."

Posted by: Lee at December 22nd, 2018 10:42 AM

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