BarcelonaThe Catalan supergrandmother She never smoked or drank alcohol. She didn’t diet either, but she survived two wars and an exile, with the nutritional deficiencies that this entails. In 117 years, Maria Branyas from Olotina never became seriously ill, and not even COVID-19 caused any symptoms. Before she died in August 2024, she learned that her cells were a decade younger than her birth date. The person who was the longest-lived in the world She knew she was special in the eyes of the scientific community and agreed to be studied by Manel Esteller, head of the cancer epigenetics group at the Josep Carreras Leukemia Research Institute (IJC), and Eloy Santos, a researcher in aging and cancer epigenetics at the center itself. It was a mystery to everyone why this woman had such an extreme life expectancy and, furthermore, with a good quality of life and good health.
According to the results of the research conducted on the biological samples Branyas gave during her lifetime, the team of scientists at the IJC confirmed their suspicions: the Catalan woman had “unmistakable” characteristics for a very elderly woman, but other much more typical and surprising ones. Traits that made her a unique human being. This is detailed by Santos and Esteller in an article published this Wednesday in the prestigious journalCell Reports Medicine, in which they describe the biological fingerprint of the Olotine super-grandmother based on her molecular profile (DNA, RNA, proteins and metabolites).
“This woman was not only a unique case because of her exceptional age: she was unique because of her biological age, which was between 10 and 15 years younger; she was unique because she had an abundant population of bifidum bacteria in her microbiota and because she had unique genetic variants,” she summarizes in the ‘.
Due to age, Branyas had lost mobility, hearing and sight, but nevertheless, until a few months before her death, she lived with a high quality of life. In fact, she had some characteristics that surprised the researchers, such as genetic variants associated with neuroprotection and cardioprotection. “They’re genes that we all have, because humans share 99.9% of our genes. However, there are some small variants that can define or make a difference. And that’s what we saw in this woman, who had genetic variants that we haven’t been able to find in any other person in Europe,” explains Santos.
A privileged machinery?
The analysis, which represents the most exhaustive study ever conducted on a supercentenarian, concludes that Branyas had three age-related traits, including shortened telomeres, which are a kind of protection at the ends of chromosomes that safeguard genetic information during cell division. As we age, these telomeres become shorter, cells don’t reproduce, and eventually die. She also had typical aging-related mutations in the production of red blood cells, white blood cells, and platelets, and a proliferation of B cells (those that generate antibodies) with altered behavior, meaning they are less effective, which often predisposes older people to more infections or extreme immune responses.
However, she also had extremely low levels of inflammation, a microbiome dominated by beneficial bifidobacteria, and a biological age younger than her chronological age, approximately a decade younger, according to epigenetic markers. “What impacted us most was the microbiota and its epigenetics,” acknowledges Santos, who also admits that they initially needed to double-check the results to ensure they hadn’t made a mistake. Furthermore, Branyas had relatives who suffered from cancer, cardiovascular disease, or even Alzheimer’s, but she never suffered from any of these diseases. “What we saw, analyzing the DNA, is that she had gene variants associated with protecting brain cognition, activating the immune system, metabolism…” the expert concludes.
Does this mean that Maria Branyas had a much more refined biological machinery than the rest of us? Although it apparently seems so, that she was born with a certain biological privilege that could have allowed her to live somewhat longer than the rest—in fact, some of her ancestors also lived many more years than the average for their time, Santos points out—it is probably lifestyle habits (and, therefore, epigenetics) that are the differential factor in understanding her health. “Genes are what our parents gave us, and with them we may reach a certain age, but our habits will surely determine how we get there,” concludes Santos.
Epigenetics depends on how we sleep, how we exercise, and whether we socialize, and the authors of the study are confident that in the future they will be able to define new strategies or assess supplementation with specific microbes based on results such as those of their analysis. “We must continue to study all of this. This study is a starting point that marks the beginning of a new field of research,” predicts Santos. At the moment, it is not known what weight genetics and habits have in extreme aging, but researchers in this field are convinced that the two must be aligned.
200 years of longevity on the rise
This is the first study in which aging can be clearly distinguished from disease, offering a comprehensive view of the effects of age on the human body. Although it is still early to link specific biological characteristics with specific habits, the researchers emphasize that a healthy diet, a stimulating and diverse social network, and the absence of toxic habits are factors that must be taken into account in explaining exceptional longevity, as demonstrated by the case of the Olotina superavia.
However, some researchers are beginning to suggest that the steady increase in life expectancy observed over the past 200 years in developed countries has stagnated, to the point that medical and healthcare advances will have little room to extend longevity as they had in . The IJC team’s goal with this study was to find clues that would explain why there are people in the world who blow out their candles year after year, well past 100 years of age, and do so in good health, as happened to Branyas for 117 years, and thus propose strategies to address this.
In this sense, the researchers assert that, for the scientific community, this study represents a turning point, since “it is the first time that such a unique person has been studied in such depth,” with so many different molecular viewpoints. “We are going to continue studying whether these variants she had have indeed been contributing to healthy aging,” explains Santos. If so, he continues, nothing says that in the future the door won’t be opened to the design of drugs that mimic these genes to prevent age-related diseases in the general population. “And we could even talk about extending the life expectancy of the population,” the expert suggests.
This research has received funding from the Generalitat (Catalan Government), the European Community, and the Ministry of Science, Innovation and Universities, as well as private support from the La Caixa Foundation, the Cellex Foundation, the Spanish Association Against Cancer, and the John and Lucille Van Geest Foundation.