SÃO PAULO, SP, BRAZIL, 6 January 2026 -- A Viewpoint published today in Genomic Psychiatry by Dr. Mayana Zatz and colleagues at the Human Genome and Stem Cell Research Center, University of São Paulo, examines why Brazil represents one of the most valuable yet underutilized resources for understanding extreme human longevity. The synthesis draws upon the team's ongoing research with a nationwide cohort of long-lived individuals while contextualizing recent advances in supercentenarian biology.
Where Genetic Diversity Meets Exceptional Aging
Why do some humans live beyond 110 years while most never approach the century mark? The question has captivated researchers for decades, yet answers remain frustratingly elusive. Part of the problem, Dr. Zatz and her co-authors argue, lies in where scientists have been looking. Most genomic datasets lack adequate representation of admixed populations, creating blind spots that may obscure precisely the protective mechanisms researchers seek.
"This gap is especially limiting in longevity research, where admixed supercentenarians may harbor unique protective variants invisible in more genetically homogeneous populations," explains Mateus Vidigal de Castro, first author of the Viewpoint and researcher at the Human Genome and Stem Cell Research Center.
Brazil offers something no other nation can match. Beginning with Portuguese colonization in 1500, followed by the forced migration of approximately 4 million enslaved Africans, then waves of European and Japanese immigration, the country developed what the authors describe as the world's richest genetic diversity. A first genomic study of a cohort of over 1000 Brazilians older than 60 revealed 2 million novel genetic variants . More than 2,000 mobile element insertions and over 140 HLA alleles absent from global genomic databases were found among older Brazilians alone. A more recent study identified more than 8 million undescribed genomic variants in the Brazilian population, with over 36,000 putatively deleterious.
The Remarkable Cohort
The research team has assembled something extraordinary. Their longitudinal ongoing study encompasses over 160 centenarians, including 20 validated supercentenarians, distributed across multiple Brazilian regions with heterogeneous social, cultural, and environmental backgrounds. Among the participants was Sister Inah, recognized as the oldest person in the world until her death on 30 April 2025 at age 116. The cohort also included the two oldest men in the world. One died last November, at age 112 while the second one is currently 113 years old.
What distinguishes this population extends beyond mere numbers. At the time of contact with researchers, some Brazilian supercentenarians remained lucid and independent in basic daily activities. Many participants come from underserved regions with limited access to modern healthcare throughout their lives, providing rare opportunity to investigate resilience mechanisms beyond medical intervention.
Familial Clusters Illuminate Heritability
One case stands out with particular clarity. A 110-year-old woman in the cohort has nieces aged 100, 104, and 106 years, representing one of Brazil's longest-lived families ever documented. The oldest one, currently aged 106, was a swimming champion at age 100. Such familial clustering aligns with prior evidence that siblings of centenarians are 5 to 17 times more likely to reach centenarian status themselves.
Can these rare familial constellations help disentangle genetic from epigenetic contributions to extreme longevity? "Investigating such rare familial clusters offers a rare window into the polygenic inheritance of resilience and may help disentangle the genetic and epigenetic contributions to extreme longevity," notes Dr. de Castro.
The Biology of Exceptional Survival
The Viewpoint synthesizes recent findings about what makes supercentenarians biologically distinct. Their peripheral blood lymphocytes maintain proteasomal activity comparable to much younger individuals. Autophagy mechanisms remain functional and upregulated, enabling efficient clearance of misfolded proteins. Single-cell transcriptomic analyses have revealed marked expansion of cytotoxic CD4+ T cells adopting transcriptional programs typically associated with CD8+ lymphocytes, a profile virtually absent in younger controls.
Recent multi-omics analysis of a 116-year-old American-Spanish supercentenarian revealed exclusive or rare variants in key immune-related genes including HLA-DQB1, HLA-DRB5, and IL7R, alongside variants in genes associated with proteostasis and genomic stability. The authors suggest immune aging in supercentenarians should not be viewed as generalized decline but rather as differential adaptation, functional resilience rather than deterioration. Interestingly differently from the American-Spanish super old woman, who followed a mediterranean diet , the Brazilian supercentenarians refer no food restriction .
Surviving COVID-19 Before Vaccines Existed
Perhaps the most striking demonstration of biological resilience came during the pandemic. Three Brazilian supercentenarians in the cohort survived COVID-19 in 2020, before any vaccination was available. Immunology assays revealed these individuals displayed robust levels of IgG and neutralizing antibodies against SARS-CoV-2, alongside plasma proteins and metabolites related to innate immune response and host defense.
How did individuals exceeding 110 years of age mount effective immune responses against a novel pathogen that killed millions of younger people worldwide? The convergence of robust immune cell function, preserved protein maintenance systems, and systemic physiological integrity makes supercentenarians an exceptional model for studying biological resilience.
Brazil's Global Position in Longevity
The statistics are remarkable. Three of the 10 longest-lived validated male supercentenarians in the world are Brazilian, including the oldest living man, born on 5 October 1912. This achievement gains significance considering that extreme male longevity is substantially less common than female longevity, attributed to factors including higher comorbidity burden, increased cardiovascular risk, and hormonal and immunological differences. Access to validated samples of female and male supercentenarians who lacked access to modern medicine provides rare scientific opportunity to investigate resilience factors in a typically underrepresented group.
Among women, Brazilian female supercentenarians in the top 15 longest-lived worldwide surpass numbers from more populous and developed countries, including the United States.
The Research Agenda
Beyond whole-genome sequencing, the team is deriving cellular lineages from selected individuals for downstream functional assays and multi-omics analyses. The goal extends beyond validating findings from non-admixed cohorts. They aim to uncover novel protective variants and mechanisms specific to the Brazilian population, discoveries that may contribute to precision medicine approaches globally relevant yet locally tailored to diverse populations. Moreover, in collaboration with the team of Prof. Ana Maria Caetano de Faria from the Universidade Federal de Minas Gerais, they will investigate the immunological profile of this cohort.
The authors issue a direct call to international longevity and genomics consortia: expand recruitment to include ancestrally diverse and admixed populations such as Brazil, or provide financial support for genomic, immunological, and longitudinal studies that deepen scientific insight while enhancing equity in global health research.
Resilience as the Central Theme
Supercentenarians represent far more than examples of extended biological survival. They embody resistance, adaptability, and resilience, precisely the qualities biomedical research must seek to unravel if the goal is not merely extending lifespan but enhancing quality of life in aging populations. Rather than merely surviving to extreme old age, these individuals actively resist the hallmarks of aging, offering insights that could reshape understanding of longevity and inform future interventions to extend health span.
"International longevity and genomics consortia should expand recruitment to include ancestrally diverse and admixed populations, such as Brazil's, or provide financial support for genomic, immunological, and longitudinal studies that deepen scientific insight and enhance equity in global health research," states Dr. Mayana Zatz, corresponding author and Professor at the University of São Paulo.
This Viewpoint article represents a critical synthesis of current knowledge regarding supercentenarian biology and the unique opportunities presented by Brazil's admixed population for advancing longevity research. By integrating findings from genomic, immunological, and clinical studies with description of an exceptional ongoing cohort, the authors offer both scientific framework and compelling case for diversifying longevity research beyond traditionally studied populations. The synthesis highlights patterns invisible in studies limited to genetically homogeneous groups while identifying the most promising avenues for understanding how some humans achieve extraordinary lifespans while remaining functional and resilient.
The peer-reviewed Viewpoint in Genomic Psychiatry titled "Insights from Brazilian supercentenarians," is freely available via Open Access, starting on 6 January 2026 in Genomic Psychiatry at the following hyperlink: https://doi.org/10.61373/gp026v.0009.
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