A groundbreaking perspective published on January 6th in Genomic Psychiatry by Dr. Mayana Zatz and her team at the Human Genome and Stem Cell Research Center, affiliated with the University of São Paulo, posits that Brazil represents a profoundly significant, yet often underappreciated, nexus for unraveling the biological enigmas of human longevity extending beyond 110 years. The researchers have synthesized decades of observations from their extensive national initiative focusing on exceptionally long-lived individuals with cutting-edge discoveries in the field of supercentenarian biology, articulating why Brazil’s unique demographic tapestry offers unparalleled opportunities for scientific inquiry.
The fundamental question of why a minuscule fraction of humanity surpasses the age of 110 while the vast majority falls short of reaching 100 has captivated scientists for generations, yet definitive answers remain elusive. Dr. Zatz and her co-authors contend that a primary impediment to progress stems from the predominantly narrow genetic scope of existing research endeavors. A substantial proportion of large-scale genomic databases are heavily skewed towards populations exhibiting considerable genetic homogeneity, consequently creating significant lacunae when it comes to understanding the biology of admixed groups. "This void is particularly detrimental in longevity research, where supercentenarians from admixed backgrounds might harbor distinctive protective genetic variants that remain undetectable within more genetically uniform populations," elaborates Mateus Vidigal de Castro, the lead author of the perspective and a researcher at the Human Genome and Stem Cell Research Center.
Brazil’s demographic evolution is a singular phenomenon, setting it apart from virtually every other nation. The nation’s history, commencing with Portuguese colonization in 1500, followed by the forced translocation of approximately four million enslaved Africans, and subsequently augmented by considerable immigration from Europe and Japan, has engendered what the authors characterize as the world’s most abundant genetic diversity. Initial genomic investigations, encompassing over a thousand Brazilians aged 60 and above, serendipitously identified around two million previously undocumented genetic variations. Among older Brazilians alone, researchers cataloged more than 2,000 mobile element insertions and over 140 Human Leukocyte Antigen (HLA) alleles that were absent from existing global genomic repositories. A subsequent, more comprehensive study further elucidated this intricate genetic landscape, reporting in excess of eight million undescribed genetic variants across the Brazilian populace, including over 36,000 identified as potentially detrimental.
The research collective has meticulously assembled a cohort of exceptional value and rarity. Their ongoing longitudinal investigation comprises more than 160 centenarians, a group that notably includes 20 validated supercentenarians, drawn from geographically diverse regions of Brazil, representing a wide spectrum of social, cultural, and environmental backgrounds. Among these remarkable individuals was Sister Inah, who, until her passing on April 30, 2025, at the remarkable age of 116, was officially recognized as the world’s oldest living person. The cohort also features the two oldest men globally; one departed last November at the age of 112, while the other currently stands at 113 years old.
The profound scientific import of this group transcends their advanced age. Crucially, when researchers initially engaged with these Brazilian supercentenarians, many exhibited remarkable mental acuity and retained the capacity for independent performance of fundamental daily activities. A significant number had spent the preponderance of their lives in socioeconomically underserved regions, with limited access to contemporary healthcare services. This circumstance provides scientists with a unique opportunity to investigate biological resilience that has demonstrably developed with minimal to no reliance on medical interventions.
A particularly illuminating example of inherited longevity is embodied by a specific family within the study. A 110-year-old woman in the cohort has living nieces who have reached the ages of 100, 104, and 106, constituting one of the most extensively documented long-lived families in Brazil’s history. The eldest niece, now 106, demonstrated extraordinary vitality by continuing to compete as a swimming champion at the age of 100. This familial pattern aligns with prior research indicating that siblings of centenarians are between five and seventeen times more likely to achieve extreme old age themselves. "Investigating such uncommon familial aggregations offers a rare vantage point into the polygenic inheritance of resilience and may facilitate the disentanglement of the genetic and epigenetic contributions to extreme longevity," Dr. de Castro notes, posing the question of whether such families can aid in differentiating genetic predispositions from environmental or epigenetic influences.
The perspective also synthesizes recent findings concerning the distinctive biological characteristics that differentiate supercentenarians from the general population. Their immune cells exhibit the remarkable capacity to maintain protein recycling systems that function at levels comparable to those of much younger individuals. Cellular waste removal processes remain robust and efficient, thereby preventing the deleterious accumulation of damaged proteins. Single-cell analyses have revealed an unusual proliferation of cytotoxic CD4+ T cells that exhibit functional attributes more akin to CD8+ immune cells, an immune profile rarely observed in younger demographics. A recent multi-omics investigation of a 116-year-old American-Spanish supercentenarian identified rare or unique variants in immune-associated genes such as HLA-DQB1, HLA-DRB5, and IL7R, alongside variants linked to protein homeostasis and genomic stability. The researchers propose that immune aging in supercentenarians should not be viewed as a general decline, but rather as a sophisticated form of adaptation that preserves critical functions. Intriguingly, in contrast to the American-Spanish supercentenarian who adhered to a Mediterranean diet, the Brazilian supercentenarians reported no dietary restrictions.
One of the most compelling demonstrations of the inherent resilience of these individuals occurred during the COVID-19 pandemic. Three Brazilian supercentenarians within the cohort successfully navigated infection in 2020, prior to the widespread availability of vaccines. Subsequent laboratory analyses revealed robust IgG responses and neutralizing antibodies against SARS-CoV-2, coupled with the presence of immune-related proteins and metabolites associated with early host defense mechanisms. The precise mechanisms by which individuals exceeding 110 years of age mounted such effective immune responses to a novel virus that proved fatal to millions of younger people remains a critical area of investigation. The authors hypothesize that the preservation of immune function, intact protein maintenance systems, and overall physiological stability collectively position supercentenarians as invaluable models for studying resilience.
Brazil’s prominence in the realm of longevity research is further accentuated by global statistical data. Three of the ten longest-lived validated male supercentenarians hail from Brazil, including the current oldest living man, born on October 5, 1912. This is particularly noteworthy given that extreme longevity is considerably less prevalent among men, who typically face heightened risks of cardiovascular disease, a greater burden of chronic illnesses, and distinct patterns of hormonal and immune aging. Access to both male and female supercentenarians who have spent the majority of their lives without the benefit of modern medicine offers an exceptional opportunity to investigate resilience in a demographic group that is typically underrepresented in such studies. Among women, Brazilian supercentenarians also occupy a significant position; the number of Brazilian women among the top fifteen longest-lived individuals globally surpasses that of more populous and economically developed nations, including the United States.
The ongoing research initiative extends beyond mere DNA sequencing. Scientists are also developing cellular models derived from selected participants to conduct functional experiments and comprehensive multi-omics analyses. The objective is not merely to corroborate findings from less diverse populations, but rather to pinpoint protective genetic variants and biological mechanisms that may be specific to Brazil’s unique population structure. These discoveries hold the potential to inform precision medicine approaches that possess global relevance while more accurately reflecting the full spectrum of human diversity. In collaboration with Professor Ana Maria Caetano de Faria from the Universidade Federal de Minas Gerais, the team also intends to conduct more in-depth studies of the immune profiles of this cohort. The authors strongly advocate for international longevity and genomics consortia to broaden their recruitment strategies to encompass ancestrally diverse and admixed populations, such as that of Brazil, or to provide financial support for genomic, immunological, and long-term studies that enhance scientific understanding and simultaneously promote equity in global health research.
Supercentenarians represent more than mere statistical anomalies of exceptionally long lives; they embody traits of resistance, adaptability, and resilience, characteristics that may prove to be as significant as lifespan itself. Rather than passively enduring the ravages of old age, these individuals appear to actively counteract numerous biological hallmarks of aging, offering invaluable insights that could significantly improve the quality of life as global populations continue to age. "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, the corresponding author and a Professor at the University of São Paulo. This comprehensive perspective consolidates current knowledge regarding supercentenarian biology with the unique insights gleaned from an exceptional Brazilian cohort. By integrating genomic, immune, and clinical findings, the authors present a compelling argument for expanding the scope of longevity research beyond traditionally studied populations, thereby revealing biological patterns that remain obscured within genetically homogeneous groups.
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