Longevity Briefs: Young People May Be Ageing Faster Than Previous Generations

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:

Cancer is an age-related disease and therefore much more likely to occur in older age. Cancer is caused by the accumulation of genetic mutations, one of the primary hallmarks of ageing. However, these genetic mutations are ultimately random, which means that young people can still get cancer even if the risk is much lower. These early-onset cancers have become significantly more common, with global rates of cancer diagnosis before age 50 increasing by around 24% between 1990 and 2019.

This has led some researchers to wonder whether younger people might be ageing faster on average than they used to. Of course younger people are undergoing ageing, but since it hasn’t progressed far enough to cause them any health problems, scientists are usually more interested in studying ageing in older people. In this study, researchers instead look back at data collected as part of long term studies in order to investigate whether successive birth cohorts are ageing more rapidly at earlier ages.

The discovery:

Researchers looked at data from 154,169 adults from the UK Biobank study, a large anonymised database containing health data from UK participants. They then used data collected from participants when they were less than 55 years-old to estimate biological age, which is an approximation of how biologically old your cells and tissues are (as opposed to chronological age, the number of years since birth). There are multiple different ways of estimating biological age using machine learning algorithms, and this study used two: PhenoAge, which combines 9 blood markers known to change with age and predict mortality and disease risk; and the Klemera-Doubal method (KDM), which combines 8 blood markers with blood pressure and ‘metabolomic ageing’ (which analyses age-related changes in metabolic compounds in the blood).

They then used these estimates to calculate the ‘age gap’ – that is to say, the difference between biological age and chronological age. If someone is 30 years old, but has a biological age estimate of 35, this could suggest that they are ageing at an accelerated pace, as their biological data looks like that of a person 5 years older than they actually are. When comparing the age gaps according to PhenoAge across different birth cohorts, researchers found that successive birth cohorts had progressively higher age gaps, with a particularly steep increase occurring around the late 1960s. People born between 1965 and 1974 had a 23% higher age gap compared to those born between 1950 and 1954. This association was present but weaker with KDM.

Interestingly, the increase appeared to be steeper for female participants. Women born in 1955 had a lower age gap than men, but this gender difference reversed over time and men born in 1970 had a lower age gap than women on average. However, researchers observed close to the opposite pattern in a smaller cohort from the US, in which age gap in men accelerated faster after starting on an equal footing.

Researchers then looked at how this apparent acceleration in biological ageing related to cancer risk. They found that for every standard deviation increase in age gap (a standard deviation is a metric of how far a value is from the average), the risk of early-onset solid cancers increased by 8%. The associations were strongest for lung cancer, gastrointestinal cancers and uterine cancer. This remained true after controlling for genetic risk factors, suggesting that this was not simply due to genetic predisposition to faster ageing being linked to cancer. Finally, researchers repeated biological age estimates using measurements of proteins linked to specific organs in order to estimate organ-specific age gaps (as some organs age more rapidly than others). They found that immune system ageing was specifically linked to early-onset lung cancer, while adipose (fat) tissue ageing was linked to early-onset colorectal cancer.

The implications:

There does indeed appear to be a generational acceleration in rates of ageing among younger age groups, and this acceleration correlates with increased cancer risk. It should be noted that this study was observational in nature, so saying that accelerated biological ageing is the cause of increased early-onset cancer is not supported by this study (which shows correlation but not causation) nor is it necessarily helpful when it comes to taking action to reverse this trend. Many lifestyle factors that promote cancer (such as smoking) alter the blood markers measured here to result in higher biological age estimates. These behaviours are indeed likely to be accelerating biological ageing, but the solution is still the same – stop smoking. What is useful about these findings is that estimating biological age may be a way to capture the effects of all of these lifestyle factors at once and tell someone if they are at risk of early-onset cancer and need to take action.

We always need to be a little careful about concluding that biological ageing has accelerated or slowed based on these kinds of studies, because biological age cannot truly be measured – only estimated based markers known to change in a predictable way with age. If biological ageing truly is speeding up in younger people, the prime suspects would be the rise in obesity rates and metabolic syndrome (some combination of high blood pressure and metabolic disturbances like high blood sugar), prolonged sedentary time, and perhaps an increase in certain environmental chemicals. Most of this is actionable, so being born later doesn’t guarantee you will age faster or be at greater risk of cancer – it may simply indicate that younger people are living increasingly unhealthy lifestyles on average.