UC Merced Professor Receives $1.78 Million to Study Extended Fasting, Sleep Apnea Effects on Mammals

Learning How the Northern Elephant Seal's Physiology Evolved and Adapted to Withstand Certain Conditions Could Benefit Humans

MERCED, CA— Deprive a healthy, average-size human of food and it's likely he wouldn't survive far beyond four or five weeks. If that same person has sleep apnea, his body will deteriorate even faster.

Northern elephant seal pups, however, live without eating for up to three months and don't appear to suffer any ill-effects. Sleep apnea isn't an issue for the adult animals either, because they go as long as 11 minutes between breathes and that doesn't appear to harm their health.

Studying how the elephant seal's physiology adapted and evolved to allow them to endure prolonged fasting and episodes of sleep apnea without suffering detrimental health consequences could help scientists identify mechanisms that could someday help humans. That is one of the primary focuses behind a new five-year $1.78 million grant obtained by the University of California, Merced.

Rudy Ortiz, an assistant professor in the School of Natural Sciences, will serve as the primary investigator and oversee a team of scientists from several universities and research institutions. The grant's sponsor is the National Heart, Lung and Blood Institute, a division of the National Institutes of Health.

"The NIH is the primary source of funding in biomedical research," said Samuel Traina, vice chancellor for research and graduate studies. "It is very competitive and typically hard for assistant professors to get this money because they don't have a long-established track record that more senior faculty has. We congratulate Professor Ortiz on this major accomplishment."

"Rudy's hard work and innovative ideas merit the recognition he has received from the National Institutes of Health," said Maria Pallavicini, dean of the School of Natural Sciences. "We are pleased for his success in obtaining this prestigious and highly competitive award. His achievement illustrates the high caliber research being completed by talented faculty at UC Merced."

The project, "Mechanisms of Oxidative Stress and Inflammation During Prolonged Fasting and Sleep Apnea," has three specific research objectives. First, investigators will analyze how elevated amounts of the hormone, angiotensin II, contributes to oxidative stress. Oxidative stress can, over time, impair how the body works. Under normal conditions, angiotensin II helps regulate blood pressure. However, inappropriately elevated levels of angiotensin II can be detrimental, causing cardiovascular complications and inflammation.

"When those compounds — lipids, proteins and DNA — get oxidized, it compromises cell integrity and they become nonfunctional," Ortiz said. "Those processes can impair the heart, liver, kidneys and the other major organs of the body."

The research team also will examine whether high levels of cortisol contributes to oxidative stress. Cortisol, a steroid found in all mammals, serves as an anti-inflammatory. When the body produces too much, it can cause lean tissue to breakdown, resulting in muscle deterioration. Northern elephant seals, however, burn about 95 percent fat during their extended fasting period and are able to conserve muscle tissue despite exhibiting elevated levels of cortisol.

"The idea is to learn how they evolved to overcome those deleterious effects," Ortiz said. That segment of the research could eventually lead to therapies to combat severe muscle deterioration such as body wasting experienced by people with AIDS, cancer or severe heart ailments.

The research team's third objective is to study the physiological reaction prompted by obstructive sleep apnea (OSA). Sleep apnea is a disorder in which breathing repeatedly stops and starts during sleep. The most common type, obstructive sleep apnea, occurs when the throat muscles relax and blocks the airway. The most noticeable sign of OSA is snoring.

In humans, untreated OSA can lead to serious health complications such as congestive heart failure. Elephant seals, however, do not appear to suffer apnea-related health complications, despite taking only four to six breaths per hour while asleep.

"No other group of mammals can do that. That is why they are such a great model to study," Ortiz said. "The idea behind our research is to reveal the mechanisms they have developed to help us better address questions in human medicine."

Ortiz's research team includes biochemistry and chemistry professor Henry Forman, a founding faculty member at UC Merced; Daniel E. Crocker, associate professor of biology at Sonoma State University; Tania Zenteno-Savin, an associate researcher at the Centro de Investigaciones Biologicas del Noreste (CIBNOR) in La Paz, Mexico; C. Leo Ortiz, a professor emeritus of biology at UC Santa Cruz; Bruce Freeman, chairman of pharmacology at the University of Pittsburgh; Dave Casper, the attending veterinarian at UC Santa Cruz and pharmacology professor Jack Roberts of the Vanderbilt University School of Medicine.

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