Genetics and stem cells

Healthy living may 'reverse' cellular ageing

"Going on a health kick reverses ageing at the cellular level, researchers say," BBC News reports. The news is based on the results of a small pilot study that looked at whether lifestyle changes can improve telomere length in men with low-risk prostate cancer. Telomere length is thought to be a genetic-level sign of ageing.

In this study, researchers investigated whether adopting a healthy lifestyle could cause telomerase activity and telomere length to increase. Telomeres are protective DNA and protein "caps" which protect the ends of chromosomes.

Telomeres naturally shorten every time the genetic information in cells is duplicated. It is believed that this leads to the ageing and death of individual cells. Telomerase is an enzyme that can add DNA to telomeres, counteracting this shortening.

The researchers found that men who adopted a healthy lifestyle had increased telomere length after five years, whereas telomere length decreased in men who did not change their ways.

While the results of the study are intriguing, this research has significant limitations, including its small sample size – only 10 men were in the intervention group, for example.

Another significant drawback is the assumption that increased telomere length will automatically lead to improved health. This remains unproven.

As the researchers concede, this interesting research will need to be continued in randomised controlled trials in larger groups.

Still, the lifestyle change interventions used in the study (see box) should, if not make you "younger", almost certainly make you healthier.

Where did the story come from?

The study was carried out by researchers from the University of California, San Francisco, San Francisco State University, and the Preventive Medicine Research Institute, California in the US.

It was funded by the US Department of Defense, the US National Institutes of Health and National Cancer Institute, and the Furlotti Family, Bahna, DeJoria, Walton Family, Resnick, Greenbaum, Natwin, Safeway and Prostate Cancer Foundations.

Three of the researchers involved in the study have commercial interests in a company that assesses telomere biology. This potential conflict of interest was made clear in the study.

The study was published in the peer-reviewed journal Lancet Oncology.

The research was well reported by most of the media, with most of the articles containing quotes from experts pointing out that this research is very preliminary. However, the Daily Express could not resist the temptation to lead with a front page headline claiming that researchers had found the "Secret of how to live longer".

This claim is misplaced. Although a healthy lifestyle probably will increase life expectancy, this study did not look at whether the men who made lifestyle changes lived longer.

What kind of research was this?

This was a small non-randomised trial. Men were not randomised to the lifestyle change or control groups, but instead were recruited into two different studies.

Larger randomised controlled trials are required to confirm the results of this study, as it is possible that differences between the participants or other unknown biases might be responsible for the differences seen.

What did the research involve?

The researchers recruited men with low-risk prostate cancer who had decided not to have radiotherapy or surgery and had instead decided to "watch and wait".

Low-risk prostate cancers are small and progress more slowly than high-risk cancers. "Watchful waiting", where no active treatment is immediately planned, is a common approach because radiotherapy and surgery can have severe side effects, such as urinary incontinence. This approach is often recommended for older men when it is unlikely the cancer will affect their natural life span.

The men participated in two studies: the GEMINAL study and the MENS study. Both studies monitored the men's tumours.

Men participating in the GEMINAL study had a complete lifestyle change. They:

  • ate a diet high in whole foods, plant-based protein, fruits, vegetables, unrefined grains and legumes, and low in fat and refined carbohydrates (meals were provided for the first three months)
  • performed moderate aerobic exercise by walking for 30 minutes per day six days per week
  • managed stress with gentle yoga-based stretching, breathing, meditation, imagery and progressive relaxation for 60 minutes daily
  • had increased social support, with 60-minute support sessions once per week

For the first three months, at each weekly session men in the GEMINAL study:

  • had another hour of moderate exercise supervised by an exercise physiologist
  • had one hour of stress management techniques supervised by a certified stress management specialist
  • attended one hour of support group led by a clinical psychologist
  • attended a one-hour lecture by a dietitian, nurse or doctor during dinner

After the first three months meetings were not compulsory, but patients could continue to meet on their own for two four-hour meetings per month.

Men participating in the MENS study did not have any help to make lifestyle changes.

The researchers monitored whether the men in both studies made lifestyle changes and calculated a lifestyle index score based on diet, stress management, exercise and social support.

Blood samples were taken from the men at the start of the studies and again five years later. The researchers measured telomere length in peripheral blood mononuclear cells (any blood cell with a round nucleus). They also looked at how active the enzyme telomerase was.

The researchers looked at whether there were differences in changes between baseline and five years after the study started between both groups of men. They looked at changes in:

  • telomere length, measured in "single-copy ratio units", a type of measurement used by geneticists to compare the size of telomeres
  • telomerase activity
  • lifestyle index score
  • prostate specific antigen (PSA) concentration

Prostate cancer can increase the production of PSA – a hormone produced by the prostate – although raised PSA levels are also found in many older men without prostate problems.

What were the basic results?

The researchers used information from 10 men participating in the GEMINAL study who underwent comprehensive lifestyle changes and compared them with 25 men who participated in the MENS study (controls).

After five years, men in the lifestyle change group made more lifestyle changes than men in the control group. Therefore, changes in the lifestyle index score were significantly higher in the lifestyle change group.

After five years, telomere length had increased by a median (average) of 0.06 telomere to single-copy gene ratio units in the lifestyle change group. It had decreased by 0.03 telomere to single-copy gene ratio units in the control group. The difference in changes was statistically significant.

When men from both groups were combined, it was found that improvements in lifestyle were significantly associated with changes in telomere length. For each per cent increase in lifestyle index score, the relative telomere length increased by 0.07 telomere to single-copy gene ratio units after adjustment for age and length of follow-up.

After five years, there was no significant difference in change in telomerase activity (the ability of the  enzyme telomerase extracted from cells to add DNA to telomeres) between the two groups, and telomerase activity was not found to be associated with changes in lifestyle.

There was also no significant difference in change in prostate specific antigen (PSA) concentrations between the two groups.

How did the researchers interpret the results?

The researchers concluded that a "comprehensive lifestyle intervention was associated with increases in relative telomere length after five years of follow-up, compared with controls, in this small pilot study. Larger randomised controlled trials are warranted to confirm this finding."

Conclusion

This interesting study has found that a comprehensive lifestyle intervention was associated with increases in relative telomere length after five years of follow-up in men with prostate cancer.

However, this is a small non-randomised study and it is possible that there are unknown sources of bias. The men came from different trials and they may have differed in other unknown ways. A randomised controlled trial is the only way to counteract this bias and this type of study needs to be performed to confirm these findings.

This research does not show whether lifestyle changes increase telomere length in groups of people other than men with prostate cancer.

Finally, although increases in relative telomere length are thought to be beneficial, it is not clear what, if any, impact this had on the men's health. For example, do longer telomeres mean a better prognosis for men with prostate cancer? 

Hopefully these questions will be answered if further research is carried out.


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