September 16th, 2013
Intense Lifestyle Changes May Lengthen Telomeres
Larry Husten, PHD
A very small pilot study offers early evidence that a program of comprehensive lifestyle changes increases telomere length. Telomeres, which have been compared to the plastic caps that prevent shoelaces from unravelling, help protect chromosomes. Telomere length is closely correlated to cellular aging: as we age the telomeres in our cells grow shorter. The new study, published online in Lancet Oncology, is one of the first studies to test whether the Nobel-prize winning research into telomeres has a role to play in assessing the health of humans in typical clinical situations.The first author of the new paper is Dean Ornish, whose career has been devoted to demonstrating the benefits of a comprehensive lifestyle program consisting of radical changes in diet and exercise, accompanied by stress management and social support. The senior author of the paper is Elizabeth Blackburn, who won the Nobel Prize for her discovery of telomeres and their significance. In the paper, Ornish and colleagues report on a long-term followup study in a small group of people with low-risk prostate cancer who agreed to follow Ornish’s rigorous program.
After 5 years, telomere length increased in this group and decreased in a group of matched controls. Adherence to the lifestyle program varied among the participants, and some members of the control group made lifestyle changes on their own. The investigators reported that change in telomere length was significantly related to the degree of lifestyle change regardless of the study group. Further, as expected, telomere shortening was independently predicted by age, but the effect of the lifestyle program was independent of age and worked in the opposite direction.
In 2008, the same group reported the 3-month results of their study showing an increase in telomerase activity in the treatment group. (Telomerase is the enzyme that repairs telomeres and is associated with telomere lengthening.) Surprisingly, however, the 5-year results found no significant differences in telomerase activity between the two groups. Prostate-specific antigen values, a measure of prostate cancer activity, also did not differ significantly between the two groups.
The authors offered the following interpretation of their study:
“Our findings are consistent with those of earlier studies, but to our knowledge this is the first study of any intervention that has shown a significant change in relative telomere length in human immune-system cells over time when compared with a non-intervention group. We noted a correlation between the degree of positive lifestyle change and increase in telomere length when all participants were assessed together, which supports the internal validity of this study. Although our sample size was small and all participants had early-stage cancer with low risk of metastasis, we believe large, randomized trials to test the validity and applicability of our results are warranted.”
In an email interview, Ornish said:
“The prospect of beginning to reverse aging on a cellular level is an important finding that may be of great interest to your readers who, I hope, will feel inspired and empowered by them. Our genes are not our fate. And now that I’ve just turned 60, it has personal meaning as well!
…
This is the same lifestyle intervention that we showed in earlier randomized, controlled trials may stop or reverse the progression of coronary heart disease and early-stage prostate cancer, as well as improve gene expression in over 500 genes in just three months. In these earlier studies, we also found a dose-response relationship between the degree of lifestyle change and the degree of improvement in a variety of metrics — the more you change your lifestyle, the more you improve — at any age.”
Donna Arnett, the president of the American Heart Association, said that the study was “interesting” and “fascinating” but pointed out that it was a very small pilot study with only 10 people in the intervention group. “The fact that they could increase telomere length is impressive,” she said. Interventions that increase telomere length are worth further study, but it will be extremely difficult to prove a link between the effect on telomeres of an intervention and an improvement in outcomes. She also noted that patients in the treatment group were “clearly a very motivated group” who had good adherence to the program. For “people with time and motivation this may be feasible… for other people this might be a challenge.”
3 Responses to “Intense Lifestyle Changes May Lengthen Telomeres”
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I just want to offer a few words of caution about this study:
There is a large gap between the conclusions of the paper, which sensibly state that the study was very small and needs to be replicated in larger populations, and Ornish’s statements, which promise that aging can be reversed at the cellular level, seemingly for all people at all ages. Here are a number of reasons why you should be very cautious before drinking this Kool-Aid, despite its resemblance to the elixir of youth.
This was not a randomized trial. Patients in the treatment group agreed to intense and highly demanding lifestyle changes. They were compared with a group who had similar risk factors but who clearly did not share their high level of motivation. There is no way to know what other important differences might exist between the two groups.
This was a very small trial. The original 2008 trial enrolled 30 patients– there were no controls– and 24 patients had sufficient blood samples to assess telomerase activity. In the new report only 10 patients had adequate blood samples available for analysis. This severely limits the generalizability of the findings.
What caused the changes (if there were changes)? The Ornish program is famous for containing multiple interventions, including drastic reductions in dietary fat and sugar, significant increases in exercise , as well as yoga classes and group therapy. There is no way to know the relative importance, or lack of importance, of any of the individual components of his program.
It is entirely possible that other, completely different interventions would have a similar effect. Last spring a paper reported that telomere length increased in people who lost weight after 5 years on the Mediterranean diet, which is not a low fat diet and which is generally thought to be much more palatable than the extreme low-fat Ornish diet.
Finally, we should be extremely cautious about the use of surrogate endpoints. There is no doubt that telomere research represents one of the most significant research advances of the last generation. But it is far too early to know if measuring telomere length is a good way to assess the value of an intervention. When it comes to surrogate endpoints we’ve been burned so many times. Let’s not make the same mistake again. This study represents an important new direction in research, but let’s not make the same mistake as Ponce de Leon. We have not yet found the Fountain of Youth.
Let me first of all pass on my appreciation to Nobel Laurate Elizabeth Blackburn and her co-author Dean Ornish for this excellent follow up study of 30 Prostate Cancer patients. I too advise my patients on life style changes without practising it personally. The differential stress response of Cancer cells and normal cells by starvation induced Sirtuin 1 upregulation was already instituted by an Ophthalmologist during his treatment phase for Prostate Cancer, overhearing this proposal for chances of reduction in side effects of chemotherapeutic drugs by starving 11 hours prior to and 8 hours following chemotherapy. Ornish’s drastic dietary changes may be doing the same I presume. I am 73 now and I will be keen to see Dean Ornish,in his 6th decade of life planning now, in another 20 years if I am lucky to be there at that time. I believe in fate and no one can alter our fate by any means. Elizabeth Blackburn to receive Nobel Prize in 2008 is her fate and no one should have changed that even. Once I see a dead patient in the hospital I imagine that as the end of all our research and all our medical specialties.
Earlier studies suggest that telomere length is an interactive function of genetic factors, environmental pathogens, and lifestyle. Shalev et al. (2013), for example, have data suggesting that stress can reduce telomere length and may even affect the programming of telomere development and shorten ultimate telomere length when traumas occur in early childhood.
More generally, there is considerable literature supporting the underlying premise of the Blackburn study – that telomere length can be influenced by environment and lifestyle. Indeed, the Blackburn study suggests at least one mechanism through which the well-supported value of the Mediterranean and similar diets in reducing morbidity and mortality might be explained. And remember Leonard’s Hayflick’s theory of aging, which has been the basis for a large body of research showing that telomerase is involved in aging and in determining an individual’s lifespan and confirming that telomerase production is influenced by certain lifestyle factors.
Thus, while the Blackburn study is small, as others point out, it provides some promise of a partial “fountain of youth.” On the other hand, given Ornish’s lifestyle viewpoint, it is important to replicate and extend this study in other laboratories, where different biases may be present.