By Christina Frangou
Bariatric surgery may reverse the shrinkage of telomeres, the caps on the ends of each strand of DNA that are considered markers for biological aging, according to a small, preliminary study presented at Obesity Week.
“This is the first study to demonstrate that surgical weight loss leads to decreased aging by increasing telomere length,” said lead author John M. Morton, MD, MPH, director of bariatric surgery, Stanford University in Stanford, Calif.
He and his colleagues presented the findings at the first annual joint meeting of the American Society for Metabolic and Bariatric Surgery and The Obesity Society.
Over the past decade, there has been increased attention focused on telomeres. Often likened to the tips on the ends of shoelaces, telomeres are responsible for maintaining chromosome stability. Every time cells replicate, the telomere frays and shortens, losing some genetic material in the process. Shortened telomeres have been linked to higher rates of cancer, neurodegenerative diseases and mortality.
But although researchers understand more about what happens as telomeres lose integrity, little is known about how to prevent it. It is believed that interventions to prevent telomere shortening could increase longevity and decrease incidence of age-related dementia (Arch Neurol 2012;69:1332-1339).
Obesity is one of the drivers of telomere shortening and experiments in mice suggest that obesity increases the formation of reactive oxygen species in fat cells and shortens telomeres (Nat Med 2009;15:996-997). Based on these findings, Dr. Morton and his colleagues set out to look at whether weight loss induced by bariatric surgery could influence telomere length.
They studied 55 patients with a mean age of 48.5 years who underwent laparoscopic gastric bypass for obesity and telomere analysis by Telomere Diagnostics, Inc.
Overall, patients’ telomere length remained relatively stable, measuring 0.987 (relative to 1.0) preoperatively and 0.982 one year after surgery (P=0.764).
But specific groups of patients showed remarkable improvements in telomere length, particularly those with the highest preoperative levels of low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP).
Patients with high preoperative CRP, defined as 7 at baseline, demonstrated a 2.83% increase in telomere length one year after surgery. Patients with high LDL-C preoperatively, defined as greater than 140 at baseline, showed a 1.62% increase in telomere length.
“I look at it this way: It’s the sickest patients—those with the worst cholesterol, the most inflammation—who got the most benefit,” explained Dr. Morton.
The findings suggest that there may be a way to determine who will have the best results from bariatric surgery, an issue that will become even more important in the next few years under health care reform, said Bruce Wolfe, MD, professor of surgery at Oregon Health & Science University in Portland. Dr. Wolfe was not involved with the study.
“A fundamental question in bariatric surgery is how can we determine beforehand who will have a very good operation so we can focus the selection of patients,” he said.
“What this study showed, as I interpret it, is that the gastric bypass and resultant weight loss led to restoration of telomere function and chromosomal preservation. If indeed the weight loss does have a positive effect on preservation of DNA and how it functions, that is a remarkable finding.”
Dr. Wolfe cautioned that although the study provides proof of concept, much more information is needed.
Currently, the investigators have expanded the study and plan to conduct telomere analysis on more than 1,500 patients who underwent gastric bypass as part of the National Institutes of Health research consortium on bariatric surgery, known as LABS. Such a study would provide more information what happens to the telomeres of bariatric surgery patients, particularly in the long term. Dr. Wolfe is co-chair of LABS.
It is unknown if telomere erosion itself contributes to aging or if it is a reflection of the aging process. That’s a question for future research, said Dr. Morton.
Dr. Morton disclosed that he has served as a consultant to Covidien and Ethicon. Dr. Wolfe reported no relevant financial relationships.