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Libbey Presentation

By Bruce Coleman
Public Affairs, University of Mississippi Medical Center

As one ages, increased, continual alcohol consumption can have a detrimental effect on ambulatory ability and cardiac function.

The science behind that conclusion was presented by Dr. Charles H. Lang during the Physiologists in Training Distinguished Lecture Nov. 6th in R153.

Lang, Distinguished University Professor, Vice Chairman of the Department of Cellular and Molecular Physiology and Professor of Surgery at the Pennsylvania State University College of Medicine, discussed his research on the metabolic effects of alcoholism in animal models, "Age-Associated Acceleration of Alcoholic Myopathy."

"Over the next 20 years, the number of folks over age 65 (in the United States) will double or triple," Lang said. "As you age, from about 40 to 60, 70 or so, you tend to lose 1-to-1 1/2 percent of your muscle mass per year. "That obviously affects the way you go about everyday activities and impacts your recovery from other stresses. The underlying mechanisms aren't well appreciated."

He said this natural process of muscle wasting with age-also known as sacropenia- may be affected by alcohol consumption. "As the U.S. population ages up, there is likewise a greater population of elderly alcoholics. The combination of this natural sacropenia and increased number of alcoholics made for an interesting study."

Unable to use humans for the study because of too many potentially confounding variables- from socioeconomic status to nutritional differences- Lang and his team concentrated on female F344 rats, which were separated into four groups: alcohol-fed adults, aged alcohol-fed adults, non-alcohol-fed adults and aged non-alcohol-fed adults. The study proved many of the team's initial hypotheses were correct, but the causality remained elusive.

"We wanted to demonstrate some evidence that some of the changes we detected were causally related to protein synthesis," Lang said. When one portion of the study that took five years to complete- involving insulin growth factor IGF-1-proved fruitless, Lang and his team decided to approach the study from a methodological perspective.

They looked at manipulating REDD1 antibody expression- particularly the potential role of increased REDD-1 on alcoholic myopathy-and mTOR signaling pathway activity. And although there are certainly more questions to be answered by the study, Lang's group was able to make the following determinations about alcohol consumption:

• Alcohol has greater catabolic effect on muscle wasting in age vs. female rats.
• Exaggerated response may be mediated by increased Deptor and REDD1.
• It inhibits mTOR activity.
• It limits involvement of protein degradative pathways, cytokines or IGF-1.
• Alcohol-induced decrease in skeletal and cardiac tissue appears to involve distinct mechanisms.
• Sustained excessive alcohol consumption by the elderly should be discouraged.

Individually, Lang said he plans on taking his team's study to heart. "As I age, I'm going to try to not drink as much and I'm going to try not to exacerbate the natural sacropenia that results," he said with a laugh.

Each year, the Physiologists In Training (PIT), consisting of graduate students and postdoctoral fellows in the Department of Physiology and Biophysics, selects the Physiologists in Training Distinguished Lecturer. According to Peter Mittwede, who introduced Lang to the audience, the group selects a speaker who is, "not only a prominent scientist and researcher, but someone who is very involved as a mentor and a teacher, encouraging the next generation of scientists."

Lang said he felt honored to be selected to deliver this year's lecture. "It's always pretty encouraging when students invite you to talk," he said. "Its particularly rewarding as a physiologist coming here to the department that Dr. Arthur Guyton founded. It's very meaningful to a physiologist of my generation. "I definitely believe I am a physiologist today because of his textbook. When I read Dr. Guyton's textbook, it really hit home to me. It's a particular honor for me to be here."