Bone hormone boosts muscle performance during exercise but declines with age

June 14, 2016

When we exercise, our bones produce a hormone called osteocalcin that increases muscle performance, according to a study publishing June 14 in a Cell Metabolism special issue on aging. Osteocalcin naturally declines in humans as we age, beginning in women at age 30 and in men at age 50. This 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.

"Our bones are making a hormone called osteocalcin that provides an explanation for why we can exercise," says Gerard Karsenty, a geneticist at the Columbia University Medical Center and senior author on the study. "The hormone is powerful enough to reconstitute, in older animals, the muscle function of young animals. Muscles and bones are close to each other, but it had never been shown before that bone actually influences muscle in any way."

During exercise in mice and humans, the levels of osteocalcin in the blood increase depending on how old the organism is. The researchers observed 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. 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.

To investigate whether osteocalcin levels were affecting exercise performance, Karsenty and his colleagues tested mice genetically engineered so the hormone couldn't signal properly in their muscles. Without osteocalcin muscle signaling, the mice ran 20%-30% less time and distance than their healthy counterparts before reaching exhaustion.

Surprisingly, says Karsenty, 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. 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," says Karsenty.

Normal "resting" levels of osteocalcin in the blood also declined with age in rhesus monkeys and humans, with the decline occuring about 15-20 years sooner in women than in men. "If you look backwards during evolution, men were much more active than women--for example, in hunting and fishing. That may be an explanation for why the decrease in circulating osteocalcin occurs later in men than in women," Karsenty suggests.

To determine the cellular mechanisms behind osteocalcin's effects, the team measured levels of glycogen, glucose, and acylcarnitines (an indicator of fatty-acid use) in mice with and without osteocalcin. The researchers determined that the hormone helps muscle fibers uptake and catabolize glucose and fatty acids as nutrients during exercise.

"It's never been shown before that bone actually influences muscle in any way," says Karsenty. "Osteocalcin is not the only hormone responsible for adaptation to exercise in mice and humans, but it is the only known bone-derived hormone that increases exercise capacity. This may be one way to treat age-related decline in muscle function in humans."
-end-
This study was supported by the NIH, the Wilf Family Foundation, an Ellison Senior Scholar Award, an EMBO post-doctoral fellowship, and the Intramural Research Program of the National Institute on Aging.

Cell Metabolism, Mera et al.: "Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise" http://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)30222-4

Cell Metabolism (@Cell_Metabolism), published by Cell Press, is a monthly journal that publishes reports of novel results in metabolic biology, from molecular and cellular biology to translational studies. The journal aims to highlight work addressing the molecular mechanisms underlying physiology and homeostasis in health and disease. Visit http://www.cell.com/cell-metabolism. To receive Cell Press media alerts, contact press@cell.com.

Cell Press

Related Hormone Articles from Brightsurf:

Hormone differences
During birth, hormones in the body surge in both mother and baby, sent along by the nervous system.

How hormone therapy slows progression of atherosclerosis
As one of the most common treatments for effectively managing menopause symptoms, hormone therapy (HT) is also known to provide multiple health benefits, including slowing the progression of atherosclerosis.

What does the "love hormone" do? It's complicated
Much of what we know about the actions of neuromodulators like oxytocin comes from behavioral studies of lab animals in standard lab conditions.

Hormone systems can still be adapted in adulthood
Behavioural biologists at M√ľnster University have now been able to demonstrate for the first time that male guinea pigs are still able to adapt their hormone systems to changes in their social environment in adulthood.

A hormone -- plant style
Researchers from the Faculties of Chemistry and Biology at Bielefeld University have now found a method that might make the production of a biologically significant precursor of jasmonic acid more efficient and cheaper.

uOttawa researchers discover new sex hormone
When University of Ottawa biologists Kim Mitchell and Vance Trudeau began studying the effects of gene mutations in zebrafish, they uncovered new functions that regulate how males and females interact while mating.

Could pancreatitis be a stress hormone deficiency?
UT Southwestern researchers find that humans and mice with pancreatitis are deficient in a stress hormone called FGF21.

Hormone therapy associated with improved cognition
Estrogen has a significant role in overall brain health and cognitive function.

Bones secrete a stress hormone
Both rodents and humans release a bone-derived hormone called osteocalcin in response to acute stress, researchers report on Sept.

'Hunger hormone' enhances memory
A team of neuroscience researchers at the University of Southern California have identified a surprising new role for the 'hunger hormone' ghrelin.

Read More: Hormone News and Hormone Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.