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Longevity Briefs: Does Having More Fat Make You Age Faster?

Posted on 15 June 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: There’s a large amount of data suggesting that people who are overweight age faster – they have shorter telomeres, more senescent cells, and develop age related diseases at a younger age. Based on our understanding of both the biology of fat tissue and the biology of ageing, it seems likely that being overweight would make you age faster – but how do we know for sure? Most of the lifestyle practices that make you overweight (such as poor diet and a sedentary lifestyle) are also associated with an accelerated rate of ageing. Does the extra fat tissue itself actually drive ageing, and does the answer to that question even matter?

What did the researchers do: In this study, researchers set out to investigate whether there was a causal relationship between excess body fat and ageing. To do this, they used a technique called Mendelian randomisation, in which researchers look at genetic predictors of various body weight metrics, rather than measuring subjects’ actual body weight. 

This approach may seem strange, but it allows scientists to eliminate environmental factors as a potential cause of accelerated ageing. Genetic inheritance is random and not influenced by the environment. This means that if people with a given gene variant are found to age faster, we can be pretty sure that the effects of that gene variant are responsible. In this study, the gene variants were identified from genome-wide association studies. They were all single letter mutations in the DNA known to influence fat tissue development and metabolism.

Researchers then compared the presence of these weight promoting gene variants to various biomarkers of accelerated ageing. These included a molecular marker (telomere shortening), a functional/clinical marker (frailty index) and a visual marker (facial ageing).

Key takeaway(s) from this research:

  • Weight-promoting gene variants were associated with significantly accelerated telomere shortening, facial ageing and frailty index
  • Bearers of weight-promoting variants were less likely to be among the 10% or the 1% longest-lived subjects
  • It is likely that fat tissue itself can promote ageing, but this study doesn’t prove this beyond all doubt

The researchers found a significant association between weight-promoting gene variants and accelerated telomere shortening, facial ageing, and higher frailty index. In particular, genetic variants associated with body fat mass and body fat percentage had a significant effect on all three metrics.

The effects of of weight-promoting variants on biomarkers of ageing in various different statistical tests. Points to the right of the central line mean longer telomeres (desirable), increased frailty index and increased facial ageing. β is a statistical measure of how much a change in one variable (the possession of weight-promoting gene variants) affects another variable (biomarkers of ageing).
Mendelian randomization supports causality between overweight status and accelerated aging

They also found that weight-promoting gene variants had a significant effect on longevity. Bearers of such variants were significantly less likely to be among the 10% or 1% of people with the longest lifespans.

Ideally, Mendelian randomisation studies pick gene variants that are linked to the variable being studied and only that variable (in this case, fat tissue). Unfortunately, that’s not always possible. In this study, the gene variants studied would also have affected other systems related to the ageing process, such as energy metabolism and resistance to the blood sugar control hormone insulin. The researchers did their best to control for these other factors, but acknowledge that the result is still imperfect. 

For all the complexity and challenges of figuring out whether a causal relationship exists, the practical implications remain simple and unsurprising: taking the steps needed to maintain a normal body weight is likely to reduce your risk of age-related disease and improve your life expectancy.

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    Mendelian randomization supports causality between overweight status and accelerated aging

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