Stem cells self-organize to form a hollow ball of cells. Credit: In Kyoung Mah, Francesca Mariani.
During exercise, muscle function needs to significantly increase; this requires that the uptake and breakdown of the two main nutrients of myofibers, glucose and fatty acids (FAs), markedly rise. The ability of bone to sense mechanical forces, the physical proximity of the two tissues, and the fact that exercise capacity and bone mass decline at the same time has long suggested that a crosstalk between bone and muscle may exist. Now, a study from researchers at the Columbia University Medical Center shows that when a person exercises, their bones produce a hormone called osteocalcin that increases muscle performance. The team states that their study describes the first bone-derived hormone known to affect exercise capacity and shows that osteocalcin injections can reverse the age-related exercise capacity decline in mice. The opensource study is published in the journal Cell Metabolism.
Previous studies show that osteocalcin naturally declines in humans as they age, beginning in women at age 30 and in men at age 50. Osteocalcin favours physiological functions that, like memory and male fertility, greatly decline with age.
This observation raises the possibility that osteocalcin may regulate other physiological processes severely affected by aging, such as muscle function during exercise. The current study uncovers a bone-to-muscle feedforward endocrine axis that favours adaptation to exercise and can reverse the age-induced decline in exercise capacity.
The current study utilised mice genetically engineered so osteocalcin couldn’t signal properly in their muscles to investigate whether this hormone’s levels were affecting exercise performance. To determine the cellular mechanisms behind osteocalcin’s effects, the group measured levels of glycogen, glucose, and acylcarnitines in mice, with and without osteocalcin. The researchers found that the hormone helps muscle fibers uptake and metabolize glucose and fatty acids as nutrients during exercise. Results show that without osteocalcin muscle signaling, the mice ran 20%-30% less time and distance than their healthy counterparts before reaching exhaustion. Data findings show that during exercise in mice and humans, the levels of osteocalcin in the blood increase depending on how old the organism is.
Results show that in 3-month-old adult mice, osteocalcin levels spiked approximately four times the amount that the levels in 12-month-old mice did when the rodents ran for 40 minutes on a treadmill. Data findings show that the 3-month-old mice could run for about 1,200 meters before becoming exhausted, while the 12-month-old mice could only run half of that distance.
The lab state that when healthy mice that were 12 and 15 months old, whose osteocalcin levels had naturally decreased with age, were injected with osteocalcin, their running performance matched that of the healthy 3-month-old mice. They go on to add that the older mice were able to run about 1,200 meters before becoming exhausted; it was extremely surprising that a single injection of osteocalcin in a 12-month-old mouse could completely restore its muscle function to that of a 3-month-old mouse. They conclude that, to their knowledge, it had never been shown before that bone actually influences muscle in any way.
The team surmise that they have shown that bones are making a hormone called osteocalcin that provides an explanation for why humans can exercise and that this hormone is powerful enough to reconstitute, in older animals, the muscle function of young animals. For the future, the researchers state that osteocalcin is the only hormone responsible for adaptation to exercise in mice and humans, and it is the only known bone-derived hormone that increases exercise capacity; therefore, this may be one way to treat age-related decline in muscle function in humans.
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