Science seeks keys to human longevity in the genetic mixing of Brazilian supercentenarians

Life expectancy in the countries with the greatest longevity, such as Japan, Italy, and Spain, hovers around 84 years. But some people live for another 30 years or so. Spaniard María Branyas, for example, lived past 117. These are the supercentenarians. And not only do they live longer, but, as was the case with the Catalan woman, they rarely reach the end suffering from cardiorespiratory problems, Alzheimer’s, or cancer, just with the ailments typical of such advanced age. Science is searching for the secret to their extreme longevity from many angles.

But scientists still hadn’t covered the southern flank. Almost all studies have been conducted with populations in the so-called first world — developed countries with access to healthcare and greater genetic homogeneity. Now, the first results of a study in Brazil are beginning to emerge. Brazil is a less developed country with limited access to modern medicine for a large part of its population and a high degree of genetic mixing. And surprisingly, it has a large number of centenarians and a significant number of supercentenarians.

Researchers at the Human Genome and Stem Cell Research Center at the University of São Paulo have compiled the largest sample of centenarians (160 and counting), including some 20 supercentenarians aged over 110. They have obtained, or are obtaining, data on their genetics and epigenetics, molecular and cellular analyses, as well as information about their ancestry, behavioral habits, and living conditions. The study includes an analysis of all the data of Sister Inah Canabarro, who was the oldest woman on the planet for a time at 116, until her death last spring. The work also includes the two oldest living men in the world, both aged 112.

“We are actively recruiting and collecting biological samples from centenarians and supercentenarians in various regions of Brazil,” explains researcher Mateus Vidigal, co-author of the ongoing research. The cohort is constantly expanding, and they expect to exceed 200 centenarians by mid-year. “Whole genome sequencing has already been completed for a substantial subset of participants, and genomic analyses are currently underway,” Vidigal adds. As the authors write in a commentary published in Genomic Psychiatry, “At the time of being contacted by our researchers, some Brazilian supercentenarians were lucid and independent in basic daily activities, such as feeding themselves.”

According to the LongeviQuest Atlas, Brazil currently has 17 living supercentenarians with validated ages. This figure is much lower than those reported by Japan and the United States. But in addition to the latter’s larger population, which inflates its figures, there is the problem of verification. “Brazil faces a well-recognized challenge in age verification due to historical gaps in civil registration, which have limited the formal documentation of many long-lived individuals,” Vidigal points out.

The Brazilian researcher points out, however, that his country is disproportionately represented among the world’s longest-living men. “In the current global ranking of the five longest-living men, Brazil holds the first and fourth positions, and until November of last year, the second position was also held by a Brazilian.” He concludes, “This pattern suggests that the Brazilian population may harbor rare longevity-related traits that remain underrepresented in international datasets.”

They don’t yet have definitive data; in fact, they are still recruiting participants. But they do offer some clues about the origin of these people’s extreme resilience. Three of the Brazilian supercentenarians survived the Covid-19 pandemic before a vaccine existed. Immunological assays have revealed that these individuals had elevated levels of IgG, the most abundant antibody in the immune system, and neutralizing antibodies against SARS-CoV-2, along with plasma proteins and metabolites related to the innate immune response. The convergence of robust immune function with preserved protein maintenance systems like those of a young person and systemic physiological integrity makes the Brazilian supercentenarians an exceptional model for the study of biological resilience.

Furthermore, unlike supercentenarians in other countries, there are no healthy diets like the Mediterranean or Japanese ones, nor comparable healthcare. “In this context, the fact that many centenarians and supercentenarians in our study reached extreme ages despite minimal exposure to modern medical interventions suggests that their biological resilience cannot be explained primarily solely by access to healthcare,” explains Vidigal. “Instead, these observations support the hypothesis that the exceptional longevity in this cohort is largely due to intrinsic factors, particularly individual genetic components.”

The explanation could lie in the high degree of racial mixing in Brazilian society. “Although the study is still ongoing, our strongest preliminary clue relates to the high level of genetic admixture in the Brazilian population,” says Vidigal. According to the researcher, “this unique genetic landscape could facilitate the convergence of protective variants derived from different evolutionary backgrounds, which could enhance biological resilience and promote exceptional longevity.”

Manel Esteller, a Catalan scientist and head of the Cancer Epigenetics group at the Josep Carreras Leukemia Research Institute, led the study on María Branyas. “Research on human aging is one of the last frontiers in the biomedical field. A key aspect of this research is the study of very elderly individuals, especially so-called supercentenarians,” he explains. “The keys to these people’s survival in relatively good health may give us clues about how the rest of the population can age healthily,” adds Esteller, who is not involved in the study of Brazilian supercentenarians.

“Until now, most studies on supercentenarians have been conducted on very specific genetic populations (Northern Europeans, Japanese, etc.), but this means we are missing a wealth of possible genetic variants that could also contribute to supercentenarianism,” Esteller points out. Indeed, this is one of the key points highlighted by the authors of the new research: the genetic mixing that underlies what Brazil is. The Amerindian population was joined, in successive waves, by the Portuguese, up to four million enslaved Africans, immigrants first from northern and then southern Europe in the 19th and 20th centuries, and, in parallel, a significant wave of Asian immigration. In fact, the South American country has the largest population of Japanese descent after Japan itself. “It’s a point that I find very interesting, and perhaps by combining DNA from such different origins in variants that provide a health and longevity advantage, we might end up producing a person over 120 years old, something we haven’t yet reliably detected on the planet,” says the Catalan researcher.

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