Healthy ageing shaped by more varied biology than previously thought

Molecular changes of ageing are far more unique than previously thought, meaning two healthy individuals of identical age can experience significantly different ageing journeys.

A new study, led by researchers at King’s College London and the most comprehensive molecular study of aging to date, demonstrates for the first time that genetic factors and environmental influences continuously interact across a person's lifespan.

The study, published in Science, observed how multiple genetic variants shape how an individual ages.

Notably, the researchers found different courses of change across participants with a gene linked to cardiac ageing (CXCL9). They also found that levels of the tumor suppressor gene Tumor Protein P53 (TP53) declined in certain individuals as they grew older, potentially altering their risk of cancer.

Such biological shifts can indicate distinct environmental exposures or reveal an underlying genetic predisposition to disease. Pinpointing individuals at higher risk offers future opportunities for earlier targeted healthcare interventions.

Importantly, the research also highlights correlations between environmental exposures, such as shifting blood levels of PFAS, commonly referred to as "forever chemicals", and evolving molecular profiles over time. This highlights how public health measures targeting environmental risks can have impacts at the molecular level.

Molecular ageing involves the steady accumulation of cellular damage alongside chemical changes in key molecules like DNA, proteins, and lipids. Over time this progression drives a gradual deterioration of tissue function, heightened physical vulnerability and a higher risk of age-related conditions including cancer as well cardiometabolic and neurodegenerative disorders.

Understanding how ageing is happening on a molecular level is vital to preventing or even reversing a range of age-related diseases - as well as increasing longevity.

Dr Julia El-Sayed Moustafa, a Research Fellow at King’s College London and first author of the study, said: “Rather than there being a single molecular roadmap of ageing, our study shows that people follow distinct biological journeys. Two healthy people of the same age can be ageing in surprisingly different ways at the molecular level. That raises the possibility of much more personalized approaches to predicting disease risk and maintaining health as we grow older.”

Over eight years the team repeatedly measured blood RNA levels, the activity levels of around 16,000 genes and hundreds of metabolites in the same 335 individuals from TwinsUK during the study, creating one of the most detailed long-term multi-omic studies of healthy ageing to date. They found that some study participants had markedly different, and sometimes opposite, molecular changes.

Ageing patterns were not uniform across the immune system, which is key to the ageing process - molecular changes over time differed between innate and adaptive immune cells. Innate immune cells are the fast, first line of defence you are born with, while adaptive immunity is a slower immune response that builds memory over time.

Our findings suggest that human ageing at the molecular level is not a uniform process, but one that is dynamic and environment dependent. Understanding individual molecular ageing trajectories may eventually help distinguish healthy ageing from the earliest stages of disease and identify opportunities for earlier, more personalized interventions. Our study could help provide a roadmap for precision medicine.”

Kerrin Small, Professor in Genomics, King’s College London