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Obesity Accelerates Aging of the Liver

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Illustration: Courtesy of Dr. Steve Horvath

Using a recently developed biomarker of aging known as an epigenetic clock, UCLA researchers, working closely with a German team of investigators, have found that obesity greatly accelerates the aging of the liver. This finding could explain the early onset of many age-related diseases, including liver cancer, in people who are obese.

Although it had long been suspected that obesity ages a person faster, it hadn’t been possible to prove the theory until now, says Steve Horvath, PhD, professor of human genetics. The research showed that carrying excessive weight can negatively affect certain tissues in the body. “This is the first study that evaluated the effect of body weight on the biological ages of a variety of human tissues,” Dr. Horvath says. “Given the obesity epidemic in the Western world, the results of this study are highly relevant for public health.”

The epigenetic clock, which Dr. Horvath developed last year, uses a previously unknown time-keeping mechanism in the body to accurately gauge the age of various human organs, tissues and cell types. He and his collaborators focused on a naturally occurring process called methylation, a chemical modification of the DNA molecule. Dr. Horvath used the clock to measure the biological age of several tissues, and it proved accurate in matching biological to chronological age in leaner people. But liver tissues from obese people tended to have a higher biological age than the researchers expected. While obesity doesn’t affect the epigenetic age of fat, muscle or blood tissue, it was found that, on average, the epigenetic age of the liver increased by 3.3 years for every 10 body mass index, or BMI, units.

For example, a woman who is 5-foot 5-inches tall and weighs 140 pounds has a BMI of 23.3. A woman of the same height who weighs 200 pounds has a body mass index of 33.3. The study found that the heavier woman’s liver would be about three years “older” than that of the lighter woman. “This does not sound like a lot, but it is actually a very strong effect,” Horvath said. “For some people, the age acceleration due to obesity will be much more severe, even up to 10 years older.”

Dr. Horvath and his team now want to determine if the premature epigenetic aging of liver tissue in obese people can be prevented, which might help reduce their risk for diseases like diabetes and liver cancer. The researchers plan to work on models that allow them to determine the exact molecular mechanisms behind this aging process — which are not known at this point — in order to find targets for therapy and prevention.

“The increased epigenetic age of liver tissue in obese individuals should provide insights into common liver-related comorbidities of obesity, such as insulin resistance and liver cancer,” the study states. “These findings support the hypothesis that obesity is associated with accelerated aging effects and stresses once more the importance of maintaining a healthy weight.”

"Obesity Accelerates Epigenetic Aging of human Liver,” Proceedings of the National Academy of Sciences, October 28, 2014


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