Telomeres are repeating gene sequences at the end of chromosomes. They protect the genetic code when cells divide and serve as indicators of cell ageing. In simplified terms: the more often a cell divides, the shorter the telomeres. Once the telomeres are used up, the cell undergoes controlled cell death. Telomeres can thus be compared to clocks that indicate cell age. Their length is influenced not only by the number of cell divisions, but also by the organism’s state of health. As a rule, a healthy lifestyle equals long telomeres. In a project funded by the Austrian Science Fund FWF, a research team headed by the physician Markus Laimer has now studied the impact on the length of telomeres of so-called “bariatric” or “metabolic” surgery, which aims at weight loss. It has been shown that the cells’ clockwork not only comes to a standstill but may even be turned back.
A nonlinear process
Some years ago, scientists thought that the shortening of telomeres was a linear process that simply reflected the number of cell divisions, recalls Markus Laimer: “The established opinion was that the telomeres are cut off regularly. At a certain point, when they are short enough, the cell will die.” But this is no longer the case, as the researcher explains. “The overall picture is much more complex than we used to think. In recent years, we have seen that it may sometimes be a wavelike process. There are indications that telomeres may alternate between shortening and lengthening.”
From previous studies it was known that the presence of certain health-damaging factors may lead to shorter telomeres. Laimer and his team were able to demonstrate this effect in a study exploring long-term developments after bariatric surgery. Gastric bypass surgery is one example of this type of intervention which aims to reduce severe obesity. “Surgery of that kind has already been shown to have diverse beneficial effects on diseases linked to obesity. They result in drastic weight loss, particularly in the first two years”, says Laimer. Beneficial metabolic effects concur, relating to diabetes risk, blood values and susceptibility to inflammation. “These effects also seem to have an impact on telomere length”, Laimer adds. He was able to show specifically that the length of telomeres increased following bariatric surgery in contrast to the general population.
Long-term study since 1998
The study of Laimer’s team builds on two studies by other research groups. One of them started in 1998 and aimed at exploring the consequences of bariatric surgery in general. “It was a very wise decision at the time to follow-up on these patients for a longer period”, notes Laimer. Telomeres were not the original reason to do so, however.
The study included 142 patients and went on for ten years. For ethical reasons it was not possible to start a control group of untreated obese individuals, because it is unacceptable to leave such patients untreated. In order to obtain comparative data, Laimer’s team therefore analysed the telomeres of normal-weight individuals from another ongoing study. As was expected, they showed a decrease of telomere length over time. White blood cells were sampled from both groups for the telomere analysis, explains Laimer’s colleague Andreas Melmer. “We employ a method going by the name of polymerase chain reaction. It enables us to make many copies of specific DNA sequences – telomeres in our case –, which we can then make luminescent.”
First evidence of long-term telomere lengthening
The novel insight was that for the first time researchers were able to demonstrate an increase of telomere length in connection with weight reduction, explains Laimer. The team also measured levels of blood lipid and blood glucose. “There were short-term studies showing a shortening of telomeres in overweight individuals. There was no effect on telomeres with short-term weight loss over one or two years, nor were there effects in weight-loss attempts using medication or dietary consulting over a longer period. We were able to show for the first time that, unlike other weight reduction methods, bariatric surgery has a long-term effect on telomeres and even results in their becoming longer again”, the researcher summarises the results.
Having meanwhile moved from Innsbruck to the University Hospital of Berne, Laimer stresses the interdisciplinary character of this basic medical research project – independent thanks to the FWF funding – and delineates it from model studies as they are conducted on mice, for instance: “Here we have a result that really demonstrates positive effects of weight-loss measures in humans.”
Markus Laimer is a specialist in internal medicine, endocrinology and diabetology at the University Hospital of Berne and a lecturer at Berne University. His research interests include the lipid and glucose metabolisms, diabetes and obesity.