A genetic study shows that the 'Catalan super-avian' had a microbiota typical of a child

GironaMaria Branyas, who died a year ago at the age of 117 in the Olot residence where she had lived for two decades, being then the oldest person in the world, she was fortunate to inherit a privileged genome that, according to researchers, made her cells "feel" and "behave" like younger cells, with a biological age of about seventeen years less. She also had a microbiota typical of a child. This is the conclusion of the study led by Manel Esteller, head of the Epigenetics Group of the Josep Carreras Institute, professor of genetics at the University of Barcelona and the world's leading authority on epigenetics and the study of aging and cancer. Numerous research teams of great international prestige have participated, the vast majority of them Catalan, and it is the most exhaustive and complete research ever carried out on a supercentenarian (those who live more than 100 years). The results, which the ARA has accessed for the first time, are revealing.

"I'm studying myself," said supercentenarian Maria Branyas to Esteller's team, convinced that the analysis of her genes and other parameters of her body, such as tissues and intestinal microbiota, could provide very valuable data for scientists to help explain the mechanisms of aging. She spent 7 years in good health. At the end of her life she only suffered deafness and joint pain and her lucidity declined only in the last few months.

Cells that "felt" younger

Through the exhaustive multiomic study carried out on Maria Branyas (of her genomic, transcriptomic, metabolomic, proteomic, microbiomic and epigenomic landscapes in different tissues), identifying and analyzing rare genetic variants through complete genome sequencing, or of her exceptional blood lipid profile, with very high levels of good cholesterol (HDL) and very low bad cholesterol (LDL).

"What we have found is one of the most efficient lipid metabolisms reported so far, a trait that has been linked to prolonged longevity and the absence of dementia," explains the study's coordinator, Manel Esteller. In addition, Maria Branyas did not have excess sugar in her blood, which prevented the risk of diabetes or obesity. The researchers have also observed, in the samples taken during Maria Branyas' life, an overrepresentation in the genes of functions such as infection control, autoimmune regulation and possibly cancer surveillance, and in genes related to neuroprotection, which contribute to the preservation of cognitive function at extreme ages. Maria Branyas also had low concentrations of glycoproteins A and B, indicating a healthy inflammatory profile that prevents the presence of systemic inflammatory diseases.

What the study has made clear is that in the case of Maria Branyas there was not a single biological process determined by a single rare genetic variant associated with healthy aging and longevity, but rather "a combination of rare variants in multiple genes and pathways (immune system, cardioprotection, aria longevity."

A microbiota more typical of a child

One of the most striking findings was in Maria Branyas' intestinal microbiota, which was "more typical of a child than a woman over a hundred years old," explains Xavier Aldeguer, coordinator of the digestive and microbiota research area at the Girona Biomedical Research Institute (IDIBGI). He and his team were in charge of analyzing Maria Branyas' stool samples, which Aldeguer personally collected from her residence in Olot a few months before her death. "We discovered a large quantity of bifidobacteria and a great diversity, which is indicative of a healthy microbiota," explains Aldeguer. The study indicates that this characteristic is linked to a control of inflammation, cognition, and bone and muscle health.

Aldeguer highlights, as also noted in the study, that during her 20 years of living in the Olot residence Maria Branyas followed a Mediterranean diet that included three yoghurts a day, and he is convinced that this helped to keep her intestinal bacteria population healthy. The IDIBGI researcher, who is very proud of having participated in this "unique" study on a supercentenarian, believes that new cases of long-lived people should be analysed to check whether Maria Branyas' microbiota profile is repeated. If the studies support this, it would be possible to "develop some types of prebiotic patterns that are associated with longevity".

Manel Esteller also points out that the study provides valuable knowledge for research into longevity, opening up avenues for the creation of drugs to delay the deterioration caused by age or to promote longevity.

However, for Esteller, one of the great novelties that the study brings is that for the first time it can be stated that age is not always associated with disease. Using the tool known as "epigenetic clocks" (which calculate the biological age of a tissue or sample), the researchers have been able to confirm that Maria Branyas "had a biological age much younger than her chronological age in the three tissues analysed", and they assure that the data suggest that one of the cells "felt" or "behaved" like younger cells, with a biological age typical of a centenarian. "This study reinforces the idea that ageing and disease can, under certain conditions, be detached, challenging the common perception that they are inextricably linked", explains Esteller.

Both Esteller and Aldeguer highlight the interest in having been able to study a supercentenarian with the characteristics of Maria Branyas: in good health, mentally lucid and totally willing to study her. "We had that opportunity in Catalonia and we couldn't let it pass us by," the researchers agree.

Mediterranean diet, no smoking or drinking

Branyas suffered from Covid in 2020, but asymptomatically and without pain. She had never smoked, drank alcohol or followed any special diet. She had an active social life until the last moment and was convinced that her genetics allowed her to live so many years in good health. However, her daughter pointed out that her ability to adapt to setbacks also helped, such as the death of her parents, husband and an 80-year-old son, and of many people in her circle of friends who she was losing as they approached 80-90 years of age. Contrary to what is often thought, her stay in the residence did not accelerate her decline, but rather it was good for her to maintain contact with other people, an orderly life and a very balanced diet, with three yogurts a day.

The study was carried out by, among others, the Josep Carreras Leukaemia Research Institute, the IDIBGI, the BarcelonaBeta Brain Research Center of the Pasqual Maragall Foundation, the High Content Genomics and Bioinformatics of the Germans Trias y Pujol Research Institute, the Catalan United Institution and dozens of other research centres from around the world.