Weight-loss surgery study compelling, inconclusive on reversing aging

ATLANTA — On Friday, media outlets trumpeted the preliminary results of a study where researchers found a change in a genetic marker associated with aging in patients who underwent bariatric surgery. Headlines blared, “Weight-loss surgery may reverse signs of aging,” and reports about the study suggested such surgery could “turn back the clock” on aging.

While the study — which is the first to look at the impact of surgical weight loss on this genetic marker — presents compelling findings, it’s still far from clear what the actual cause of this genetic change was in patients who had gastric bypass surgery and what follow-up studies might reveal about the workings of this and other weight-loss surgeries.

The study from Stanford, which involved 51 patients, found a lengthening of telomeres, a region at the end of DNA strands. Study author Dr. John Morton compared these telomeres to aglets, the plastic tip that holds the threads at the end of a shoelace together. Past research has linked their shortening with aging.

Just over half of the 51 patients saw this increase, and they were the patients who appeared to have worse markers prior to their surgery, specifically their levels of LDL (“bad”) cholesterol and C-reactive protein (CRP), which is produced in the liver and whose level in the body increases with inflammation.

But patients in the study had an average body-mass index of 44.3 (a “normal” BMI is between 18.5 and 24.9, above 30 is obese). Patients with morbid obesity have a number of conditions that can accompany that weight, such as Type 2 diabetes and heart or respiratory diseases, which in turn can make interpreting a study such as this one difficult.

“All of those things impact aging,” said Morton, the chief of bariatric surgery at Stanford University Medical Center and president-elect of the American Society for Metabolic and Bariatric Surgery.

“There’s multiple reasons why you could have seen this improvement,” Morton went on to tell Al Jazeera, noting that the patients were followed for a year and there are changes in things like diet and exercise that occur after the operation. It’s hard to distinguish what role these lifestyle changes may play in results found following surgery.

Depression may also play a role.

“Obese patients in general, they have a high degree of depression,” said Dr. Jaime Ponce, director of bariatric surgery at Chattanooga Bariatrics in Tennessee and immediate past president of ASMBS. He said it is estimated that 70 to 80 percent of obese patients suffer from some form of depression, from mild to severe. This can be because of issues stemming from the obesity, such as discrimination and lifestyle limitations.

Depression, which has also been associated with telomere length, can be improved following bariatric surgery.

“By losing weight with bariatric surgery, it allows them to improve that depression score,” Ponce said. “Over follow up, even at four, five, six years they maintain a better depression score than before surgery.”

So while the change in telomere length may be caused by a number of factors, the discovery could eventually help patients who might benefit from, but for whatever reason are not good candidates for, weight-loss surgery if researchers can find another way to achieve the result.

While 18 million Americans might benefit from some form of bariatric surgery, Morton said, less than 1 percent of them undergo the procedure. There are a number of reasons behind that, such as access to care, insurance coverage and concerns from patients about getting surgery.

If researchers can confirm the results and understand what causes the change in telomere length, they might be able to understand how to manipulate that pathway. Such research might allow for a medication rather than surgery, Morton said.

“Potentially, that’s something that’s down the road,” Morton said. “And at least we know where to look.”

“We’ll figure out what’s driving it,” Morton added. “It’s a very cool thing, we can maybe figure out what is it that will allow us to change the telomeres. I don’t know. We may come up with something that allows us to manipulate or change the aging process, which I think would be important. The big question: Is it reflective of the aging process or is it driving the aging process? ... I think those are always the questions we’ve got to ask in studies.”

Even if telomere length does turn out to be a benefit of gastric bypass surgery, that doesn’t mean all weight-loss surgeries will show a similar benefit.

“The different operations are so mechanistically different that they cannot be put in the same bin,” said Dr. John Kral, a researcher and former surgeon at SUNY Downstate Medical Center in Brooklyn, who attended Morton’s presentation. “Everything is different about them.”

For example, gastric bypass, which was the type used on patients in Morton’s study, affects the body’s metabolism, which will play a role in the changes seen afterward. You can’t necessarily expect the same results in, for example, lap-band surgery, where a change in metabolism is not the main mechanism, Kral said. There are four main types of bariatric surgery, and each is done differently and may lead to different outcomes.

But Kral reflected the sentiments of other physicians when he said the results found in the study echo what he already tells patients.

“Obesity is premature aging, if we cut premature aging we’re lengthening the lifespan,” Kral said. “If you have a successful operation done by a competent surgeon your expectation is you’re going to be lengthening your life, with or without a change in your telomere length.”