Molecular study of world’s oldest living person reveals new secrets of healthy ageing

When the oldest living person in the world died at just under 117 and a half years of age in August 2024, her own account of how she had managed to live for so long was already enough to inform practical interventions that can help ensure healthy ageing. But now, an international team of researchers led from the Cancer Epigenetics Group of Josep Carreras Leukaemia Research Institute and the University of Barcelona, Catalonia, Spain, have been able to provide a rare insight into the biology of extreme longevity through the use of multiomics techniques to study the molecular processes that enabled her to live such a long and healthy life. The results of their study are published in the journal Cell Reports Medicine*.

Maria Branyas Morera was born in the United States and moved to Spain at the age of eight. She lived through two world wars, the Spanish civil war, and the Spanish flu and Covid-19 pandemics. She contracted Covid at the age of 113, and subsequently made a full recovery. The researchers were intrigued by someone who had not only had an exceptionally long, but also a very healthy life, and set out to try to discover more about the factors involved.

They investigated the full range of her genome, transcriptome (mRNA), metabolome (metabolites), proteome (proteins), microbiome (microorganisms) and epigenome (the chemical changes in DNA), and compared the results with those from other very old people. Indeed, several markers showed her advanced age and closeness to death, particularly her telomeres, which were too short for DNA stability. This is usually considered to be a precursor of age-related disease.

“But few have studied the separation of healthy versus unhealthy ageing. Our study was one of the first to look at the possible reasons for a disconnect between these processes. Telomere length was a good example of this dissociation,” says Dr Manel Esteller, the study’s principal investigator.

Indeed, Señora Branyas was lacking in many molecular markers of age-associated disease. The analysis showed that she had advantageous genetic variants as well as efficient cholesterol and lipid metabolism, linked to longer life and to good cognitive health. Low levels of inflammation helped her to avoid diabetes and cancer, and her microbiome contained high levels of ‘good’ bacteria. Finally, epigenomic investigation showed that her biological age was way below her chronological age.

“Our results have helped us identify factors that may help many older people live longer, healthier lives. We have, for example, identified particular genes that are associated with healthy longevity, and that can therefore be new targets for drug development. Most importantly, Señora Branyas’ data confirm that having a good cardiolipidic and metabolomic profile is linked to a longer and better life. We know from her own account that she avoided eating too much fat and processed sugars. Finally, her avoidance of tobacco and alcohol and regular consumption of yoghurt will have played an important role in her healthy ageing,” says Dr Esteller.

The researchers believe that their results will provide further proof of the concept that ageing and disease are not inseparable, and point to many ways in which nutritional and other health advice can aid older people live healthier lives. They hope that their data will also guide strategies for future research into therapies that can strengthen the protective traits they uncovered.

“Señora Branyas told us: ‘Please study me so I can help others’. And she has! Though we found that healthy ageing is a highly individualised process without any one major feature involved – rather, it is many small factors working together – we think that being able to show so clearly the characteristics that lead to healthy, as opposed to unhealthy, ageing will be advantageous in the future for all, both young and old,” said Dr Esteller.

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* Santos-Pujol E. et al, 2025, The Multiomics Blueprint of the Individual with the Most Extreme Lifespan,  Cell Reports Medicine https://doi.org/10.1016/j.xcrm.2025.102368