The enduring human aspiration for a longer, healthier life has driven scientific inquiry for centuries, yet the most profound secrets of extreme longevity—particularly the biology of individuals living beyond 110 years, known as supercentenarians—remain largely unraveled. A recent viewpoint published in Genomic Psychiatry by Dr. Mayana Zatz and her research team at the University of São Paulo’s Human Genome and Stem Cell Research Center posits that Brazil, with its exceptionally diverse population, represents an overlooked yet profoundly important global laboratory for unlocking these mysteries. Their insights, stemming from extensive national studies and contemporary discoveries in supercentenarian biology, highlight Brazil’s unique potential to advance our comprehension of human resilience and aging.
For decades, scientists have grappled with the fundamental question of why a select few individuals defy typical lifespans, reaching ages well past 110, while the vast majority do not even attain 100 years. The scarcity of definitive answers, according to Dr. Zatz and her co-authors, is partly attributable to the concentrated focus of much existing research. Many expansive genomic databases predominantly feature genetically homogeneous populations, leading to significant voids in our understanding of admixed groups. Mateus Vidigal de Castro, the primary author of the viewpoint and a researcher at the Human Genome and Stem Cell Research Center, emphasizes this limitation, explaining that "this particular gap is especially restrictive in longevity studies, where supercentenarians from admixed ancestries might possess unique protective genetic variations that are simply not observable in more genetically uniform populations." Such variants could hold the key to understanding extraordinary resistance to age-related diseases.
Brazil’s demographic evolution distinguishes it as a nation with virtually unparalleled genetic diversity. The historical confluence of distinct populations began with Portuguese colonization in 1500, followed by the tragic forced migration of approximately four million enslaved Africans. Subsequent waves of immigration from various European countries and Japan further enriched this genetic melting pot. This intricate history has forged what the authors accurately describe as the world’s most genetically diverse population. Early genomic investigations involving over a thousand Brazilian individuals aged 60 and above unveiled around two million previously uncharacterized genetic variants. Specifically within the older Brazilian demographic, researchers identified more than 2,000 mobile element insertions and over 140 HLA alleles that were absent from global genomic repositories. A subsequent, broader study further expanded this scope, reporting more than eight million undescribed genetic variants across the entire Brazilian populace, including over 36,000 deemed potentially detrimental. This vast genetic landscape offers an unprecedented opportunity to discover novel factors influencing extreme longevity.
The research team in São Paulo has meticulously cultivated a truly exceptional and invaluable cohort for their ongoing longitudinal study. This group comprises more than 160 centenarians, including 20 rigorously validated supercentenarians, who originate from widely diverse geographical regions across Brazil and possess a broad spectrum of social, cultural, and environmental backgrounds. Among the participants was Sister Inah, who achieved global recognition as the world’s oldest living person prior to her passing in April 2025 at the age of 116. The cohort also included two of the world’s oldest men, one of whom passed away at 112 last November, while the other is currently 113 years old. This concentration of extreme age, particularly among men where longevity is less common, provides unique research material.
What makes this particular group of supercentenarians especially insightful transcends their advanced age alone. When the researchers initially engaged with them, several Brazilian supercentenarians exhibited remarkable cognitive sharpness and maintained the ability to independently manage fundamental daily activities. A significant number of these individuals spent the majority of their lives in underserved regions with extremely limited access to modern healthcare facilities. This crucial detail allows scientists to investigate intrinsic biological resilience that developed largely without the influence or intervention of contemporary medical practices, offering a clearer view of natural human robustness.
The study has also illuminated compelling instances of inherited longevity within families. One participant, a 110-year-old woman, is part of a family unit that includes nieces aged 100, 104, and 106, marking it as one of the most long-lived familial clusters ever documented in Brazil. The eldest niece, at 106, notably remained an active swimming competitor even at the age of 100. This familial pattern aligns with prior research indicating that siblings of centenarians possess a significantly elevated likelihood, between 5 and 17 times greater, of reaching extreme old age themselves. Dr. de Castro highlights the scientific value of such occurrences: "Investigating these rare familial groupings offers an extraordinary opportunity to observe the polygenic inheritance of resilience, potentially aiding in the differentiation of genetic and epigenetic contributions to extreme longevity." These insights are crucial for disentangling the complex interplay of factors that contribute to an extended lifespan.
The viewpoint further synthesizes recent scientific findings on the distinct biological attributes that set supercentenarians apart from the general population. Their immune cells, for instance, maintain protein recycling systems that operate with an efficiency comparable to much younger individuals. Cellular cleanup processes, critical for removing damaged components, remain vigorously active and effective, thereby preventing the detrimental accumulation of dysfunctional proteins. Single-cell analyses have also revealed an unusual expansion of cytotoxic CD4+ T cells in these individuals, which surprisingly exhibit functional characteristics 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 uncommon or exclusive genetic variants in immune-related genes, such as HLA-DQB1, HLA-DRB5, and IL7R, alongside variants linked to protein maintenance and genomic stability. The authors contend that immune aging in supercentenarians should be conceptualized not as an overall decline, but rather as a sophisticated form of adaptation that actively preserves critical functions. Interestingly, in contrast to the American-Spanish supercentenarian who adhered to a Mediterranean diet, the Brazilian supercentenarians reported no specific dietary restrictions, suggesting diverse biological pathways to extreme longevity.
One of the most compelling demonstrations of the remarkable resilience inherent in this cohort emerged during the initial stages of the COVID-19 pandemic. Three Brazilian supercentenarians participating in the study successfully survived SARS-CoV-2 infection in 2020, prior to the widespread availability of vaccines. Subsequent laboratory analyses showcased robust IgG responses and potent neutralizing antibodies against the virus, accompanied by the presence of immune-related proteins and metabolites associated with early host defense mechanisms. The fundamental question of how individuals over 110 years old could mount such effective immune responses to a novel virus that proved lethal to millions of younger people remains a pivotal area of inquiry. The authors propose that a combination of preserved immune function, intact protein maintenance systems, and overall physiological stability collectively positions supercentenarians as powerful living models for studying resilience.
Brazil’s significant standing in global longevity research is further accentuated by international demographic data. Three of the ten longest-lived validated male supercentenarians globally are Brazilian, including the oldest living man, born on October 5, 1912. This statistic is particularly noteworthy because extreme longevity is considerably less prevalent in men, who typically face elevated cardiovascular risks, a higher incidence of chronic illnesses, and distinct patterns of hormonal and immune aging. Access to both male and female supercentenarians who have lived most of their lives largely without modern medical intervention presents an unparalleled opportunity to study resilience in a demographic often underrepresented in such studies. Among women, Brazilian supercentenarians also feature prominently; the number of Brazilian women listed among the world’s top 15 longest-lived individuals surpasses that of more populous and economically affluent nations, including the United States.
The ongoing research efforts extend beyond mere DNA sequencing. Scientists are actively developing cellular models derived from selected participants to conduct sophisticated functional experiments and multi-omics analyses. The primary objective is not simply to corroborate findings from less diverse populations, but rather to pinpoint protective genetic variants and unique biological mechanisms that may be specific to Brazil’s ancestrally rich population. These discoveries could fundamentally inform precision medicine strategies that are not only globally pertinent but also more accurately reflect the breadth of human genetic diversity. In collaboration with Professor Ana Maria Caetano de Faria from the Universidade Federal de Minas Gerais, the team is also poised to delve deeper into the immune profiles of this exceptional cohort.
The authors emphatically urge international longevity and genomics consortia to broaden their recruitment efforts to encompass ancestrally diverse and admixed populations, such as Brazil’s. Alternatively, they advocate for providing substantial financial backing for genomic, immunological, and long-term longitudinal studies that promise to deepen scientific understanding while simultaneously fostering equity in global health research. Dr. Mayana Zatz, the corresponding author and a Professor at the University of São Paulo, articulates this call to action, stating that "global longevity and genomics collaborations ought to expand their participant recruitment to include genetically diverse and admixed populations, like Brazil’s, or allocate financial resources to genomic, immunological, and longitudinal studies that enhance scientific insight and promote fairness in worldwide health research."
Ultimately, supercentenarians offer more than mere examples of extraordinarily long lifespans. They embody resistance, adaptability, and profound resilience—qualities that may prove just as vital as lifespan itself. Rather than passively enduring the ravages of old age, these remarkable individuals appear to actively counteract numerous biological hallmarks of aging, providing invaluable clues that could enhance the quality of life as global populations continue to age. This viewpoint masterfully integrates current knowledge of supercentenarian biology with groundbreaking insights from an unparalleled Brazilian cohort. By synthesizing genomic, immune, and clinical data, the authors construct a compelling argument for transcending traditionally studied populations in longevity research, thereby revealing crucial patterns that remain obscured within genetically homogeneous groups.
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