Molecular changes associated with ageing vary far more between individuals than previously thought, meaning two healthy people of the same age can experience very different biological ageing journeys. A new study led by researchers at King’s College London provides the most comprehensive molecular analysis of ageing to date. It shows that a single biological pathway does not govern ageing.

Published in Science, the study demonstrates that genetic factors and environmental influences continuously interact throughout a person’s lifespan, shaping how their biology changes over time. Researchers observed how multiple genetic variants influence ageing and found striking differences between individuals, including variations involving CXCL9, a gene linked to cardiac ageing.

The researchers also found that levels of the tumour suppressor gene Tumour Protein P53 (TP53) declined in some individuals as they aged, potentially affecting their risk of cancer. Such molecular changes may reflect different environmental exposures or reveal an underlying genetic predisposition to disease. Identifying these patterns could eventually help pinpoint people at higher risk and allow healthcare interventions to begin earlier.

Environmental factors also appeared to influence individual ageing trajectories. The researchers identified correlations between changing blood levels of PFAS, often known as “forever chemicals”, and evolving molecular profiles. The findings suggest that environmental exposures can leave measurable biological signatures over time and that public health measures aimed at reducing environmental risks could potentially have effects at the molecular level.

Molecular ageing involves the gradual accumulation of cellular damage and chemical changes affecting important molecules such as DNA, proteins and lipids. Over time, these processes can contribute to declining tissue function, increased physical vulnerability and greater risk of age-related conditions, including cancer, cardiometabolic diseases and neurodegenerative disorders. Understanding these molecular processes could therefore be important for preventing age-related diseases and promoting healthier longevity.

“Rather than there being a single molecular roadmap of ageing, our study shows that people follow distinct biological journeys,” said Dr Julia El-Sayed Moustafa, a Research Fellow at King’s College London and first author of the study. She explained that even two healthy people of the same age can be ageing in surprisingly different ways at the molecular level, opening possibilities for more personalised approaches to predicting disease risk and maintaining health.

Over eight years, researchers repeatedly measured blood RNA levels, the activity of around 16,000 genes and hundreds of metabolites in 335 participants from TwinsUK. This created one of the most detailed long-term multi-omic studies of healthy ageing conducted to date. The researchers discovered that participants sometimes experienced markedly different, and even opposite, molecular changes as they grew older.

Ageing patterns also differed across the immune system, with changes varying between innate immune cells, which provide the body’s rapid first line of defence, and adaptive immune cells, which develop immune memory over time. Professor Kerrin Small, Professor in Genomics at King’s College London, said the findings show that molecular ageing is dynamic and influenced by the environment. Understanding these individual trajectories could ultimately help distinguish healthy ageing from the earliest stages of disease and provide a roadmap towards more precise, personalised healthcare.

More information: Julia El-Sayed Moustafa et al, Longitudinal dynamics of gene expression and metabolomics in an aging population cohort, Science. DOI: 10.1126/science.aed6452

Journal information: Science Provided by King’s College London