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Longevity

Longevity Briefs: What Determines Your Chances Of Living To Age 100?

Posted on 8 April 2024

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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.

The problem:

We know that centenarians – people who reach their 100th birthday – are biologically different from the rest of us. They often have fewer markers of ageing and less age-related morbidity than people several decades younger than them. But how did they get there? One way of trying to answer that question is to compare people at younger ages, see which people become centenarians, and investigate which factors predict exceptional longevity. That’s what this study did, by looking at molecular markers in the blood.

The discovery:

Researchers looked at over 44,000 Swedish subjects who had blood tests in the 80s and 90s as part of a large cohort study, the AMORIS study. The participants were at least 65 years old at the time of the first blood test. Researchers then analysed associations between the levels of various blood markers and the likelihood of becoming a centenarian.

They found that even decades before their 100th birthday, there were significant differences between centenarians-to-be and their shorter lived counterparts. Those who became centenarians had higher levels of total cholesterol (more on this later) and iron than non centenarians of similar age. The 20% of participants with the lowest iron levels were about 73% as likely to reach age 100 as the 20% of participants in the middle of the range for iron levels. For total cholesterol, that figure was 80%.

For other compounds, lower levels were associated with an improved chance of reaching age 100. Some standouts were glucose (sugar), uric acid (a waste product of nutrient breakdown) and creatinine (also a waste product of protein digestion and muscle breakdown, not to be confused with creatine).

The implications:

Can the results of this study tell us anything about how we can increase our chances of living longer? The general theme of the markers identified in this study was that they were all related to diet and inflammation and/or to liver and kidney function (since these organs are involved in clearing substances like uric acid from the blood.) These observed differences may be cases of correlation and not causation. Elevated uric acid for example can drive inflammation, but is also an indicator of worse kidney function. People with worse kidney function in their 60s are probably less healthy in general, so of course they are more likely to live to 100 than those with better kidney function. However, based on what we think we know about the role of nutrition and inflammation in ageing, it’s quite plausible that many of these markers do influence your chances of becoming a centenarian, and that these chances could be increased through lifestyle practices that modify said markers.

It’s worth taking some extra time to talk about the finding that higher total cholesterol was associated with increased probability of becoming a centenarian. This seems surprising given the link between cholesterol and heart disease. Research does show that both high and very low levels of cholesterol are associated with increased mortality, but there may be more to the story. Previous studies actually suggest that higher total cholesterol is associated with higher mortality up until age 60, but is linked to lower mortality thereafter and especially in very old age. There’s also some evidence that the children of centenarians are more likely to have elevated cholesterol. It’s not clear exactly what’s going on here. Cholesterol is important for things like brain function and hormone production, so it may be that in the oldest old, the benefits/risk ratio shifts in favour of higher total cholesterol. However, you still need to avoid cardiovascular disease somehow. Perhaps centenarians have inherited metabolic traits that let them maintain higher cholesterol levels without the downsides, allowing them to survive into very old age without suffering cardiovascular problems. In other words, deliberately raising your total cholesterol in the hope of living longer isn’t likely to be a very good idea.


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    References

    Title image by Marcel Eberle

    Blood biomarker profiles and exceptional longevity: comparison of centenarians and non-centenarians in a 35-year follow-up of the Swedish AMORIS cohort https://doi.org/10.1007%2Fs11357-023-00936-w

    The association of apolipoproteins with later-life all-cause and cardiovascular mortality: a population-based study stratified by age https://doi.org/10.1038%2Fs41598-021-03959-5

    Unique Lipoprotein Phenotype and Genotype Associated With Exceptional Longevity https://jamanetwork.com/journals/jama/fullarticle/197486

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