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Longevity

Longevity Briefs: Does Cutting Calories Slow Ageing?

Posted on 14 February 2023

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Calorie restriction (CR) generally means reducing one’s calorie intake significantly (say 20-30% below recommended daily intake) without causing malnutrition. Studies in various animal models suggest that CR can have a range of health benefits, including delaying the onset of age-related diseases and extending lifespan, suggesting an overall slowing of the rate of ageing. 

While CR seems to have health benefits in humans, we don’t know whether it slows the ageing process or extends lifespan in our species, as most calorie restriction trials don’t last more than a few years at most. One thing we can do is to estimate the rate at which someone is ageing over a given period of time. The most common approach for this is to use epigenetic clocks – algorithms that estimate someone’s biological age based on molecular ‘tags’ called methyl groups that are added to the DNA molecule as we age.

What did the researchers do: In this study, researchers looked at data from the CALERIE trial, which was a randomised trial of CR taking place in the US. The participants were all of normal weight or slightly overweight, and were between the ages of 21 and 50. Participants were randomly assigned to either eat normally or follow a caloric restriction diet, consisting of a 25% reduction in calorie intake for two years. Researchers measured participants’ epigenetic age using three different epigenetic clocks at various points in time. For most participants, measurements occurred at the beginning of the study, at 12 months, and at the end of the study.

Key takeaway(s) from this research:

  • According to DunedinPACE epigenetic clock, CR resulted in a 2-3% reduction in the rate of ageing compared to those eating normally.
  • Two other epigenetic clocks showed no significant effect.
  • Participants in the CR group had improved metabolic health.

According to an epigenetic clock called DunedinPACE, CR resulted in a modest but significant 2-3% reduction in the rate of ageing compared to those eating normally. While this may not sound like much, even a 1% reduction in the rate of ageing would have a very significant impact on public health. However, the two other epigenetic clocks – called GrimAge and PhenoAge – did not show significant reductions in the rate of ageing.

Changes in epigenetic age of participants in the CR group (red) and ad libitum (blue) over 2 years as measured by three epigenetic clocks. For the first two graphs, age on the Y axis is shown in years. Thus participants epigenetic age is expected to increase by two years. In the last graph, epigenetic age is shown as a % change relative to the expected measurement. A value of 0 would mean that participants are ageing normally. A value of -0.01 means participants have an epigenetic age that is 1% lower than expected.
Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial

The three clocks differ mainly in which cells they get their DNA from, which original study was used to develop the algorithm, and what additional information (such as lifestyle factors) is incorporated into the biological age estimation. DunedinPACE uses DNA from whole blood samples and is considered an accurate estimator of epigenetic age.

What does this mean in practice? That’s difficult to say. Calorie restriction could reduce your rate of epigenetic ageing, but keep in mind that is just one facet of the ageing process, and we still don’t really know how well it corresponds to ageing as a whole. The study did also find significant improvements in metabolic health: people in the CR group had reduced body weight, lower blood sugar on average and responded better to insulin, the hormone that controls blood sugar. This is certainly a desirable outcome, but once again, we don’t know much about how long these benefits last.


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    References

    Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial: https://doi.org/10.1038/s43587-022-00357-y

    Title image by Kim Cruickshanks, Unsplash

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