Multiomic study of world's longest-lived person gives insights into ageing

Extremely advanced ageing and poor health are not intrinsically linked, according to a study of the longest-lived supercentenarian.

Supercentenarians are people who live until or past their 110th birthday. An international team of researchers collected blood, saliva, urine and stool from a supercentenarian one year before she died at 117 years old. These samples were used to study the genome, epigenome, transcriptome, metabolome, proteome and microbiome of the supercentenarian. They found that although her body showed clear signs of extreme ageing, a number of biological factors protected her from diseases that normally have higher incidence in the final years of life.

'She had an exceptional genome enriched in variants in genes that are associated with enhanced lifespan in other species, such as dogs, worms and flies,' Professor Manel Esteller, who led the study at the Josep Carreras Leukaemia Research Institute in Barcelona, Spain, told the New Scientist.

The study published in Cell Reports Medicine reports that the supercentenarian had unquestionable signs of ageing, such as very short telomeres and an aged population of B lymphocytes. However, she also presented a combination of rare variants in multiple genes, associated with cardioprotection and neuroprotection likely promoting her longevity. Blood analyses also revealed she had very low levels of inflammation and very efficient cholesterol and fat metabolism, which are protective against common diseases such as diabetes and cardiovascular disease.

The researchers also identified that the supercentenarian retained a gut microbiome typical of a much younger person, with high levels of Bifidobacterium, which have been linked to low levels of inflammation. Finally, the team tested the biological age of the supercentenarian, by creating an epigenetic clock based on her pattern of DNA methylation and found that she was 23 years younger than her chronological age.

Nevertheless, the supercentenarian's habits and environment could have also shaped her longevity, as she did not drink alcohol or smoke, adhered to a mediterranean diet and ingested high amounts of yogurt.

Professor of biogerontology, Richard Faragher, from the University of Brighton, who was not involved in the research told the New Scientist that the study demonstrated how many tests are now available to longevity researchers. However, he cautioned that this is a case report of one person and there is a 'danger that a slightly unusual variant in, for example, a gene can be turned into a scientific "just-so story" about its relevance to ageing'.

The findings presented in this study provide insight into human ageing and suggest biomarkers of healthy ageing and potential strategies to increase life expectancy. However, further studies are necessary with larger cohorts before extrapolating the findings to the general population.