Extra pounds cause the liver to age faster, potentially explaining why obesity is linked to diseases like liver cancer and insulin resistance, new research suggests.
It's not clear if this ageing directly translates to higher risks of certain diseases. Still, it's possible that "people whose liver is much older than expected need to be screened more carefully for various diseases even if they managed to lose a lot of weight," said study author Steve Horvath, a professor of human genetics and biostatistics at the University of California, Los Angeles School of Public Health.
Epigenetic ageing is the ageing rates of various tissues in the body. "According to the epigenetic ageing clock, the vast majority of tissues, cell types and organs age at the same rate," Horvath said. But these ageing rates may differ from person to person.
Read: Diverse ageing rates puzzle scientists
"Some people are clearly older than others. Genetics plays a big role," Horvath explained. "Twin studies show that about 40 percent of the variation in epigenetic age is genetic."
Why we age
The goal of the new study was to "understand why we age", Horvath said. "One way of tackling this question it to understand which factors relate to the epigenetic age of different human tissues. Although many people probably suspected that excessive weight ages the body, there was no objective way of demonstrating such an effect," he said.
The researchers reached their conclusions by studying 1,190 samples of human tissue, including samples from more than 130 livers. They found that the epigenetic age of the liver grew by 3.3 years for each 10 "body mass index" units. The BMI is a measurement of whether a person's weight and height are proportionate; 10 units refers to the difference between BMIs of, say, 35 and 25.
"Assume there is a man who is 5-foot-8 and weighs 130 pounds. This slender man would have a body mass index of 20," Horvath said. "Compare him to a man of the same age and height who weighs 230 pounds. The liver of this obese man – who has a BMI of 35 – would probably be five years older than that of the slender man."
The researchers found that weight-loss surgery didn't have any effect on the age of the liver. However, the study only looked at surgeries within the previous nine months, Horvath noted.
The researchers don't know how excess weight may affect the liver, but they found some clues. "We found a very strong adverse effect on liver tissue but we did not find any effect in fat, muscle or blood," Horvath said.
No cause-and-effect proven
While an association between obesity and accelerated liver ageing was found, a cause-and-effect link was not proven.
Dr. Trygve Tollefsbol, director of the Cell Senescence Culture Facility at the University of Alabama at Birmingham, said the study "provides a unique way of looking at ageing not only in terms of aging of the liver but also in terms of epigenetic ageing." The findings are important because a liver that ages more quickly may make a person more likely to develop cancer, Tollefsbol added.
Read: Liver cancer (primary)
Horvath said the next step for research is to understand if epigenetic aging rates will help doctors diagnose diseases in obese people or at least figure out which diseases they should be monitored for. "Ultimately, this line of research might lead to therapeutic interventions that not only keep the liver young but also the rest of the body," he said.
The study appears in the Proceedings of the National Academy of Sciences.
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