Rare genetic condition offers new insights into human aging process

Scientists have discovered a rare genetic condition which causes people to age at a much faster rate, offering fresh insights into the aging process. 

The study shows for the first time how a 'biological clock' present in every cell of the body could contribute to age-related diseases. 

Experts say the findings could support the design of future medicines to counter diseases linked to older age, as life expectancies continue to rise across the globe. 

Marks on DNA, known as DNA methylation, accumulate over time and can be used to accurately measure a person's age. This DNA methylation clock 'ticks' at different rates in mammals according to lifespan, going faster in animals with a shorter life expectancy. 

However, it has not been known whether this biological clock directly contributes to aging, or simply measures time. 

An international group of scientists, led by the University of Edinburgh, uncovered a new accelerated aging syndrome in humans – Heyn-Sproul-Jackson syndrome (HESJAS) – in which methylation marks occur at the same locations on DNA as in normal aging, but at a much quicker rate. 

Health issues and tissue changes that occur in old age were seen in those with HESJAS much earlier, connecting DNA methylation to multiple age-related disease processes. These included decreased blood cell production, which is linked to increased susceptibility to infections, as well as osteoporosis and hair loss. 

In a mouse model of the condition, increasing DNA methylation marks also led to changes in metabolism associated with diabetes and high cholesterol levels. 

As DNA methylation marks accumulate in mice, adult stem cells – which are crucial for repairing and renewing tissues – fail to function properly, offering a possible explanation for the decline in tissue function linked to disease. 

Further studies are planned to pinpoint how DNA methylation is involved in reducing tissue renewal and to investigate ways to reverse these changes, the research team says. 

That marks on someone's DNA can precisely predict their age has fascinated me for a long time. It has been exciting to be able to discover a rare human genetic disorder, that helps us understand this clock's role for all our long-term health in old-age. This study has only been possible because of very many generous, often co-located colleagues, who contributed their diverse skills to this work." 

Professor Andrew Jackson, study lead, Institute of Genetics and Cancer

Professor Joris Veltman, Director of the Institute of Genetics and Cancer, said: "By studying a rare disease in depth, our colleagues have gained new insight into the biology of human aging and identified promising directions for future rejuvenation therapies. This study shows the power of international collaboration, bringing together 76 researchers from seven countries." 

The study, funded by the European Research Council and the UK Medical Research Council, is published in the journal Nature Genetics: https://www.nature.com/articles/s41588-026-02633-8 

The international research team also included scientists and doctors from the University of Cambridge, the Institute of Cancer Research in London, the Spanish National Research Council, the Spanish National Cancer Research Centre and hospitals across France, Norway, Mexico, New Zealand and the USA.