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expert reaction to study looking at omega-3 and biological ageing in humans

A study published in Nature Aging looks at the effects of of omega-3, vitamin D and exercise on biological ageing.

 

Prof Dame Linda Partridge FRS FMedSci, Weldon Professor of Biometry at the Institute of Healthy Ageing, UCL; Biological Secretary of the Royal Society; and Founding Director Emeritus of the Max Planck Institute for the Biology of Ageing, said:

“The press release describes a study that is part of a clinical trial and is hence experimental rather than observational in nature, greatly reducing the likely involvement of confounders.  The team previously found that intake of omega-3 alone reduced the rate of infections by 13% and the rate of falls by 10%, and that all three interventions (omega-3, vitamin D, exercise at home) combined had a significant additive benefit on reducing prefrailty by 39% and incident invasive cancer by 61% over a 3-year follow-up.  The press release inadvertently gives the misleading impression that these findings came from the current study.

“The new study aimed to understand the molecular basis of the beneficial effects, and to develop biomarkers.  Clinical trials that investigate the effects of interventions to improve health during ageing have two big challenges.  First, there are multiple possible outcome measures because many aspects of health could be affected, and this can bring statistical problems.  Second, it may take a long time for any benefits to become apparent.  For both reasons, biomarkers are needed that report on the pathways to health improvements and that can predict clinical outcomes before they happen.

“The biomarkers investigated were derived from several well authenticated DNA methylation clocks.  These clocks are trained to predict biological, as opposed to chronological age.  Individuals differ in the speed of change in their DNA methylation clocks and can thus be characterised as slow or fast agers.  These clock age deviations can be better predictors of time to death than chronological age.

“Omega-3 intake alone had slowed 3 of the 4 clocks used at the end of the 3-year trial period, and those individuals that started with lower omega-3 levels showed the largest response.  All 3 treatments together slowed one of the 4 clocks.  Omega-3 treatment thus had the greatest effect on the clocks.  However, whether there is any direct link between the molecular events mediating the responses of the methylation clocks and the improvements in health awaits further study.

“The limitations of the work are well discussed.  The study population was relatively healthy and homogeneous and longer term effects of the interventions are unknown.  The study was well conducted, and consistent with other studies showing slowing of molecular biomarkers of ageing by interventions that improve health at later ages.”

 

Dr Julian Mutz, King’s Prize Research Fellow, King’s College London, said:

“Evaluating the effectiveness of preventative strategies and interventions in improving health span (i.e., how long individuals live in good health) is challenging due to the long human lifespan.  Epigenetic aging clocks provide a proxy measure of biological aging and have the potential to play a crucial role in studies assessing such interventions.  While most research on biological aging and health-promoting interventions has been cross-sectional (examining correlations between epigenetic age and factors such as diet at a single time point), this study provides important preliminary evidence that epigenetic aging may slow over three years in response to intervention.

“The authors identified a beneficial effect of daily omega-3 supplementation, particularly in individuals with lower baseline omega-3 levels.  However, no such effect was observed for vitamin D or a three-day-per-week home exercise program.  These findings contribute valuable new data but given the relatively small sample size (98 participants receiving omega-3 and 95 receiving a placebo) and the sample’s composition, which is healthier than the general population, the results should be considered preliminary.  Future trials should aim to assess the generalisability of these findings, including in younger populations.”

 

Dr Mary Ni Lochlann, NIHR Research Fellow in Geriatric Medicine, Centre for Ageing Resilience in a Changing Environment, King’s College London, said:

“It’s exciting to see these results showing the benefits of omega-3, vitamin D and exercise on ageing.  While the study was focused on healthy and active older adults, and led to a relatively small improvement in their ageing-biological-clocks, it adds to the growing evidence that these simple and fairly low-cost interventions are beneficial and, based on this and previous existing research, worth engaging in for adults as they get older.”

 

Prof Kevin McConway, Emeritus Professor of Applied Statistics, Open University, said:

“This is an interesting study.  It has some important limitations, as the researchers themselves make clear.  I think these put important boundaries around the evidence it can provide on the effects on aging of the treatments used in the clinical trial.  There’s just too much that we don’t know yet.

“The press release mentions a key limitation, that there is no agreed gold-standard measure of biological aging.  Because of that, the researchers concentrated on four different biological clocks, but they also presented results on another two older biological clock measures in the main research paper, and indeed present a few findings on another two in the supplementary data tables.

“These biological aging clocks were all developed by taking measurements of certain types of biomarker in large samples of people, and comparing them with the people’s chronological ages and death rates.  But the details of how the developers of the clocks analysed these data and produced their biological aging measures were different from one another, and there isn’t (yet) agreement on the best way to do that.  So the researchers on this new study analysed their data using several clocks, and reported the results from all of them.

“I think it makes good sense to look at several clocks, but we have to take into account that they give different information about the effect of the treatments in the trial, and it’s not possible to say that the findings from one biological clock are better than those from another clock.

“There is a certain amount of consistency on the findings, in that trial participants who took the omega-3 supplement had biological aging clocks that aged (on average) less over the three years of the study than was the case in people who didn’t take that supplement, at least for the main ‘clocks’ that the researchers considered.  But there was a lot of statistical variability between people in how big this change in biological aging actually was, and there were also quite substantial differences in the estimates of the changes based on different biological clocks.

“One of the biological clocks produced the very neat finding that the three interventions in the trial (vitamin D supplements, omega-3 supplements, and a home exercise programme) seemed to add up in their effects, so that participants who had two of three interventions had more slowing of their biological clocks than those who had only one, and the clocks of those who had all three interventions had yet more slowing of their biological clocks.

“But that doesn’t mean that this particular clock is getting at an underlying truth more reliably than the other clocks, that don’t show this additive pattern.  We just can’t say yet – because the study hasn’t yet produced relevant results beyond its three-year duration.  The authors write, “Whether the DO-HEALTH treatments resulted in a persistent slowing of biological aging, leading to the prevention or delay of frailty and chronic disease beyond the 3-year follow-up, is currently unknown.”  (DO-HEALTH is the name of this clinical trial.)

“Likewise, they mention that they don’t have data on long-term survival rates of the people in the study.  Maybe one of the other clocks will eventually turn out to relate more closely to survival rates and future health.  Maybe the pattern of how the effects of the three interventions combine will be different.  We just can’t say yet.

“Also we can’t say whether the effect on biological aging clocks will continue after three years, because that wasn’t studied.  Maybe taking omega-3 supplements for longer will have a greater impact on biological aging, or maybe it won’t.  And the study doesn’t indicate what the effect on these biological clocks would be if people, who had been taking a supplement, stop taking it.

“This study is an interesting start, but there’s so much that it can’t tell us.

 

Further information

“Other findings from the same clinical trial have already been published, and some is mentioned in the new paper near the beginning.  (There’s more at https://do-health.eu/.) For example, taking the omega-3 supplement reduced the rate of infections, and of falls.  People who took both supplements and also participated in the home exercise programme, all together, had a substantial reduction in cancer diagnoses (61% over three years) compared to people who had none of these interventions, and also did better on measure called pre-frailty, based on weakness, fatigue, weight loss, low walking speed and low activity level.

“Whether people were classed as ‘robust’, pre-frail or frail depended on how many of these five measures were below par.  (None below par meant they were robust, just one or two meant they were classified as pre-frail, more than that would classify them as frail.)  The trial looked at people who started out as robust (that is, satisfactory on all these measures) and saw how many moved to being pre-frail or frail, and having all three interventions (the two supplements and the exercise) reduced pre-frailty by 39%.  It didn’t have a clear effect on frailty, measured in this way, but that was probably just because very few participants moved from being robust all the way to frail in the three-year period.

“The press release seems (to me) to imply that these findings were part of the new research.  They aren’t, though they do come from the same clinical trial and involved some of the same researchers.  (Also, to nit-pick, the press release refers to ‘frailty’ whereas the findings are actually about pre-frailty, a somewhat different concept.).”

 

 

‘Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial’ by Heike A. Bischoff-Ferrari et al. was published in Nature Aging at 16:00 UK time on Monday 3 February 2025. 

 

DOI: 10.1038/s43587-024-00793-y

 

 

Declared interests

Prof Dame Linda Partridge: “None.”

Dr Julian Mutz: “No COIs.”

Prof Kevin McConway: “Previously a Trustee of the SMC and a member of its Advisory Committee.”

For all other experts, no reply to our request for DOIs was received.

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