Jun 6, 2008    #056
Contact: John Austin

Mechanism of muscle aging is focus of UMKC School of Nursing research Findings by Marco Brotto and colleagues to be published in prestigious scientific journal

Researchers at the University of Missouri-Kansas City (UMKC) School of Nursing may be on the verge of unlocking a key mechanism when it comes to understanding what causes the gradual decrease in muscle strength as people age. Their findings will be published in an upcoming issue of Aging Cell, one of the world’s leading scientific journals devoted to research involving the biology of aging.

The fact that muscles tend to get smaller and weaker as a person ages, a process known as sarcopenia, is a not fully understood yet. A big part (approximately 50 percent) of the decrease in muscle strength is thought to occur simply because muscles become smaller. What about the remaining 50 percent?

Put simply, the answer may be calcium, according to Marco Brotto, B.S.N., M.S., Ph.D., associate professor at the UMKC School of Nursing.

“But it has nothing to do with the amount of calcium that a person intakes,” he said. “But rather, how much of that calcium actually makes its way into muscle cells.”

A decrease in muscle strength develops in the aged population despite interventions — such as increased physical activity and improved diet — and leads to debilitating injuries, loss of independence and reduced quality of life. A healthy lifestyle is important in delaying sarcopenia (and it is fundamental for prevention of cardiovascular diseases, diabetes and obesity), but even in healthy individuals, when they become 75 or older, sarcopenia develops.

“Therefore, understanding the cellular mechanisms that contribute to aging-related muscle weakness is essential for the development of effective treatments and improved care for the elderly,” Brotto said.

In their research, Brotto and his colleagues have shown for the first time that store-operated calcium entry (SOCE) — the mechanism through which calcium is absorbed into muscle and tissue cells — is compromised in aged skeletal muscles.

“SOCE is essential for keeping optimal levels of calcium inside the intracellular compartments that store calcium,” Brotto said. “This is needed for muscles to contract well. If there is less calcium inside these intracellular stores, then less calcium is available for contraction and muscles become weaker.”

Since SOCE is needed for muscles to perform well — and study findings suggest that this mechanism is compromised in aged muscles — Brotto and his fellow investigators propose that this could be the “missing link” in identifying the cause for muscle weakness during aging.

The next steps in the research will involve identifying the molecular basis for this defective mechanism and at what point in a person’s lifecycle this defect begins to express itself. The various aspects of ongoing studies are currently being developed in collaboration with Brotto’s colleagues — Drs. Jianjie Ma, Xiaoli Zhao and Noah Weisleder — at Robert Wood Johnson Medical School (RWJMS). Zhao and Weisleder are co-first authors in the paper and Jianjie Ma is a University Named Professor at RWJMS and long-time collaborator with Brotto.

“In addition, we have begun a new collaboration with Dr. Michael Wacker at the UMKC School of Medicine and St. Luke’s Hospital here in Kansas City. Our next step will be to perform some biochemical and functional studies in muscles from human patients with sarcopenia,” Brotto said. “Our goal is to expand our studies to the bedside and beyond. The environment and expertise at UMKC is unique and should allow us to take our basic research findings from the lab and eventually into the community.”

The University of Missouri-Kansas City (UMKC), one of four University of Missouri campuses, is a public university serving more than 14,000 undergraduate, graduate and professional students. Celebrating 75 years, UMKC engages with the community and economy based on a three-part mission: visual and performing arts, health sciences, and urban engagement.

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