One of the most fascinating questions in science is what distinguishes those who live past 100 from the majority of the population. Part of the answer, according to an article published on January 6 in Genomic Psychiatry, lies in the genetic diversity present in the Brazilian population. The hypothesis is that genetic admixture could be a contributor to the longevity and quality of life observed in centenarians and supercentenarians.
This insight emerged from the collection of clinical data and biological samples from more than 100 centenarians – 20 of them supercentenarians – from different social and cultural backgrounds across Brazil. The research team is part of the Human Genome and Stem Cell Research Center (HUG-CELL) at USP, led by geneticist Mayana Zatz. Together, they conducted genomic and cellular analyses of participants in the cohort, which included highly functional individuals who survived Covid-19 when no vaccine was yet available. The researchers emphasized that all results presented are considered preliminary.
“The ultimate goal of the study is to identify which factors determine this extreme longevity. We know this depends mainly on genetics and the immunological profile. We are identifying genetic variants in these centenarians and studying their function”, Zatz told Jornal da USP.
According to her, the intention is for the results to help other people achieve longevity – but above all, to do so while remaining healthy and with a good quality of life. The next step is to investigate the immune profile of the sample, in collaboration with professor Ana Maria Caetano of the Federal University of Minas Gerais (UFMG).
Supercentenarians represent a unique sample of human longevity, characterized by resilient immunological, genetic, and metabolic profiles against aging-associated decline. These are the properties the authors believe may offer strategies to extend life expectancy for all. In Brazil, there are more than 37,000 people aged 100 or older, according to the 2022 Census, which makes the country a potential hub for research into human longevity. Even so, most databases still lack genetic samples from admixed populations, such as Brazil’s.
As Brazil is home to some of the greatest genetic diversity in the world – resulting from the mixing of different peoples, including Europeans, Africans, and Indigenous groups – researchers are interested in addressing this gap.
As Mateus Vidigal, first author of the article, explained, “the current scientific literature focuses on the Caucasian population. Some genes and variants replicate in our population, others do not, and new variants need to be cataloged due to admixture – variants that were not seen before because studies considered a more homogeneous population”.
What also draws the authors’ attention are the different realities of these groups. “Compared with the European population, Brazilians are more vulnerable”, Vidigal pointed out. “In Europe, older adults, due to socioeconomic conditions and public policies, have greater access to medicine – something Brazilians lack to a large extent, in general. But, on the other hand, there are individuals in Brazil who live past 100 and maintain well-being even without access to healthcare”, he added. The explanation for this resilience, he said, lies in genetics.
In the view of João Paulo Limongi França Guilherme, coauthor of the article, studying an admixed centenarian population will be extremely valuable for the future, “to create guidelines for new interventions aimed not only at aging, but at healthy aging”. A researcher at HUG-CELL, he added that the team intends to collect more samples over the next five years and is recruiting people over 95, although the preference is for older individuals.
The secret in the genetics of supercentenarians
The study found that supercentenarians are genetically distinct in certain biological mechanisms. For example, their peripheral blood lymphocytes maintain proteasomal activity – responsible for removing damaged or unnecessary proteins within cells- comparable to that of younger individuals. Another observation concerns autophagy mechanisms, the natural cellular recycling process, which remained functional and regulated in these individuals
In addition, João Paulo Guilherme explained that there is a major difference in hormone regulation among supercentenarians. “Hormones signal to the body so that it functions properly. In this case, hormones that should decrease, such as those associated with sexual characteristics, seem to be more preserved in this population. And this has a direct effect on a series of cells that should decline along with those hormones”.
Based on these findings, the authors argued that immune aging in supercentenarians should not be viewed as decline, but rather as functional resilience. The research uses the term to describe the immunological stability of cellular functions. “Whereas it is normal for most of the population in their 70s and 80s to experience functional decline – when cells start to age and lose their natural characteristics – supercentenarians do not,” he added.
“The cells of supercentenarians seem to be younger cells, more resistant to aging. The decline of these cells does not happen as expected” – João Paulo Guilherme, researcher at the Human Genome and Stem Cell Research Center (HUG-CELL)
However, even though there are points of convergence in the study sample, researchers noted that each individual’s lifestyle differs. “There are centenarians who are lucid, active, and independent. Several participants live alone; some engage in physical activity”, explained Mateus Vidigal. The reverse also applies: “There is a portion that does not have healthy habits, some are sedentary, consume alcohol, others are smokers. Not everyone is lucid and active. Yet they lived past 100. We attribute this to a genetic factor”.
Vidigal noted that the team’s interest in the “genetics of aging” dates back to 2017, when, in his research project, the plan was to compare people who reached 100 with quality of life with those who also reached 100 but with health problems. Covid-19 changed the course of the investigation, which sought centenarians infected with the disease. “Because of the pandemic context, we studied the resilience behind such a severe disease in this age group. In 2020, nobody had been vaccinated. So we were studying a natural resilience in an individual who lived past 100”, he said.
Among the research participants, the nun Inah Canabarro Lucas – known simply as Sister Inah – stands out. She was recognized by LongeviQuest as the world’s oldest living person from December 29, 2024, until her death on April 30, 2025, at the age of 116. The study also includes a familial case involving a 109-year-old woman with nieces aged 100, 104, and 106, making them one of the longest-lived families recorded in Brazil’s history. The middle sister, Laura de Oliveira, began swimming after the age of 70 and is a South American record holder.
The researcher noted that, even though the findings are preliminary, two patterns already stand out: women live longer than men, and shorter individuals appear to have a higher likelihood of living longer, especially women.
The group is currently recruiting volunteers aged 100 or older who would like to take part in the study. Interested individuals can contact the team by email: dnalongevo@usp.br.
The article Insights from Brazilian supercentenarians is available here.
More information: mayazatz@usp.br, with Mayana Zatz; mateusvcastro@gmail.com, with Mateus Vidigal, and jplfguilherme@hotmail.com, with João Paulo Guilherme.
*Intern under the supervision of Tabita Said
English version: Nexus Traduções, edited by Denis Pacheco
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