Rise in cancer before 50: the clue offered by biological age

Cancer remains closely linked to the passage of time, but in recent decades some tumours have been diagnosed more frequently in adults under the age of 50. This increase does not affect every type of cancer equally, nor does it mean that most cases now occur among younger people. However, the trend is sufficiently clear in colorectal, uterine and other gastrointestinal cancers to raise an important question: what is happening in more recent generations? Research published in Nature Medicine points to one possible piece of the puzzle: accelerated biological ageing.

Growing older is not exactly the same as ageing. Chronological age advances at the same pace for everyone: one year every twelve months. Biological age, by contrast, attempts to reflect the condition of the body through factors such as inflammation, metabolism, immune function and the ability of tissues to repair themselves. Two people born on the same day may have the same age on the calendar but very different physiological profiles.

To estimate it, researchers use biological clocks, models that combine different indicators to calculate whether the body appears to be ahead of or behind what would normally be expected. One of the tools used in the new study was PhenoAge, which integrates a person’s chronological age with nine blood measurements, including glucose, creatinine and C-reactive protein. The result does not reveal how old someone “really is”, but whether their profile resembles that of a person with a higher or lower risk of disease and mortality than usual for their age.

The study analysed 154,169 UK Biobank participants under the age of 55. Although early-onset cancer is usually defined as cancer diagnosed before 50, the researchers extended the limit because the increase appears to continue among people aged between 50 and 54. They then repeated the calculations using the standard threshold and obtained similar results. To determine whether the trend also appeared in another population, they used data from the US All of Us Research Program.

When the researchers compared people of similar chronological ages who had been born at different times, they found that more recent generations tended to have a more advanced biological age. The pattern appeared in both the British and US populations and remained consistent across different calculation methods. This does not mean that every younger person is ageing faster, but rather that the findings describe a general trend with substantial variation between individuals.

The next step was to examine whether the gap between chronological and biological age was associated with the later development of tumours. During follow-up, people whose biological ageing was more advanced had a 15% higher risk of developing an early-onset solid tumour than those with the youngest biological profiles. The association was especially noticeable in lung, gastrointestinal and uterine cancers, and was weaker among cancers diagnosed after the age of 55.

The researchers also investigated whether different parts of the body might age at different rates. They analysed thousands of proteins in the blood and used models associated with specific organs and tissues. Ageing of the immune system was linked to a higher risk of early-onset lung cancer, while ageing of adipose tissue was associated with colorectal cancer. These findings still need to be confirmed, but they suggest that the body does not age as a single unit.

Why might accelerated ageing favour the development of cancer? For an altered cell to form a tumour, accumulating mutations is not always enough. The environment surrounding that cell also matters. Persistent inflammation, metabolic changes, reduced immune control and difficulties repairing tissue may allow certain cells to survive and multiply. In the digestive system, for example, visceral fat, inflammation and changes in the gut microbiome may act together.

Biological age could therefore act as a marker that brings together the effects of many different exposures. Diet, physical inactivity, obesity, sleep disruption, pollution, environmental substances and social inequalities may act over many years and affect several systems at once. The study did not identify which of these factors explains the generational change. Its contribution lies in detecting a possible shared consequence: some people reach middle age with greater physiological wear than expected.

This does not prove that biological ageing directly causes the rise in early-onset cancers. This was an observational study, which can identify a relationship but cannot demonstrate that one phenomenon causes the other. Although the analyses accounted for body mass index, smoking, alcohol consumption, diet, physical activity, previous illnesses and genetic predisposition, other factors may not have been measured accurately. It is also possible that the earliest changes caused by an undiagnosed tumour alter certain blood values, making the body appear biologically older.

Another limitation concerns how biological ageing is measured. Biological clocks are built using statistical calculations, and they do not all reflect exactly the same processes. The fact that several tools pointed in a similar direction strengthens the findings, although the associations were not identical in every analysis. In addition, a large proportion of the sample came from the United Kingdom, and some models still have limited validation among younger people and populations from other countries.

For now, there is no biological-age value above which a person should be considered at risk. Calculating biological age cannot determine whether someone will develop cancer, nor does it justify changing the age thresholds used in screening programmes. Before these indicators can be introduced into clinical practice, researchers will need to follow more diverse populations and carry out repeated measurements to determine whether they genuinely improve prediction beyond the risk factors already known.

The study therefore does not resolve why certain cancers are increasing among younger adults, but it offers a different way of investigating the phenomenon. Instead of searching for a single responsible exposure, it examines the accumulated effect that the environment, lifestyle and metabolism may leave on the body. If more recent generations are reaching biological changes traditionally associated with older age at an earlier stage, this acceleration could help create conditions that favour the development of some tumours. Confirming this possibility could improve our understanding of the increase and support new opportunities for prevention.