A Viewpoint published on January 6 in Genomic Psychiatry by Dr. Mayana Zatz and colleagues at the Human Genome and Stem Cell Research Center at the University of São Paulo argues that Brazil may be one of the most valuable yet overlooked places to study extreme human longevity. The article draws on the team's ongoing nationwide research involving exceptionally long-lived individuals while also summarizing recent scientific advances in the biology of supercentenarians.
Why Living Past 110 Remains Hard to Explain
Why do a small number of people live beyond 110 years when most never come close to 100? Researchers have long been fascinated by this question, but clear explanations have remained out of reach. According to Dr. Zatz and her co-authors, one reason may be where scientists have focused their efforts. Many large genomic databases lack meaningful representation of admixed populations, which can hide important biological clues.
“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 a researcher at the Human Genome and Stem Cell Research Center.
A Population Shaped by Extraordinary Genetic Diversity
Brazil's population history gives it a genetic profile unlike that of any other nation. Portuguese colonization beginning in 1500, the forced migration of roughly 4 million enslaved Africans, and later immigration from Europe and Japan produced what the authors describe as the richest genetic diversity in the world.
This diversity is already revealing itself in genetic studies. An early genomic analysis of more than 1000 Brazilians over age 60 uncovered about 2 million previously unknown genetic variants . Researchers also found more than 2,000 mobile element insertions and over 140 HLA alleles that do not appear in global genomic databases. A later study expanded these findings, identifying over 8 million undescribed variants across the Brazilian population, including more than 36,000 considered potentially harmful.
A Rare and Remarkable Longevity Cohort
The research team has assembled a cohort that few countries can match. Their ongoing longitudinal study includes more than 160 centenarians, among them 20 validated supercentenarians, drawn from many regions of Brazil with diverse social, cultural, and environmental backgrounds. Participants included Sister Inah, who was recognized as the world's oldest living person until her death on 30 April 2025 at age 116.
The cohort also included the two oldest men in the world. One passed away last November at age 112, while the other is currently 113 years old.
Longevity Without Lifelong Medical Support
What makes this group especially informative is not just their age. When first contacted by researchers, several Brazilian supercentenarians were still mentally alert and able to manage basic daily activities on their own. Many spent much of their lives in underserved areas with limited access to modern healthcare, offering a rare chance to study biological resilience that developed largely outside medical intervention.
Families That Reveal Inherited Longevity
One family in the study provides a striking example of how extreme longevity can cluster across generations. A 110-year-old woman in the cohort has nieces aged 100, 104, and 106, making it one of the longest-lived families ever documented in Brazil. The oldest niece, now 106, was still competing as a swimming champion at age 100.
This pattern aligns with earlier research showing that siblings of centenarians are between 5 and 17 times more likely to reach extreme old age themselves.
Can cases like this help separate genetic influences from environmental or epigenetic factors? “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,” says Dr. de Castro.
What Makes Supercentenarians Biologically Different
The Viewpoint also brings together recent discoveries about how supercentenarians differ at the biological level. Their immune cells maintain protein recycling activity similar to that seen in much younger people. Cellular cleanup processes remain active and efficient, helping prevent the accumulation of damaged proteins.
Single-cell transcriptomic studies show a notable expansion of cytotoxic CD4+ T cells that behave more like CD8+ immune cells, a pattern rarely observed in younger individuals.
A recent multi-omics study of a 116-year-old American-Spanish supercentenarian identified rare or exclusive variants in immune-related genes such as HLA-DQB1, HLA-DRB5, and IL7R, along with variants linked to protein maintenance and genome stability. The authors emphasize that immune aging in supercentenarians should not be seen as uniform decline, but as a form of adaptation that preserves function. Interestingly differently from the American-Spanish super old woman, who followed a mediterranean diet , the Brazilian supercentenarians refer no food restriction .
Surviving COVID-19 at Extreme Old Age
The COVID-19 pandemic offered a striking real-world test of resilience. Three Brazilian supercentenarians in the cohort survived COVID-19 in 2020 before vaccines were available. Laboratory testing showed strong IgG responses and neutralizing antibodies against SARS-CoV-2, along with immune-related proteins and metabolites associated with early host defense.
How individuals over 110 years old mounted effective immune responses to a brand-new virus that killed millions of younger people worldwide remains an open question. The authors suggest that preserved immune function, intact protein maintenance systems, and overall physiological stability together make supercentenarians an exceptional model for studying resilience.
Brazil's Place Among the World's Longest Lives
Brazil's contribution to extreme longevity is reflected in global records. Three of the ten longest-lived validated male supercentenarians are Brazilian, including the oldest living man, born on 5 October 1912. This is notable because extreme longevity is far less common in men, who generally face higher cardiovascular risk, more chronic disease, and different hormonal and immune aging patterns.
Access to verified samples of both female and male supercentenarians who lived most of their lives without modern medical care offers a rare opportunity to study resilience in a group that is often underrepresented in research.
Among women, Brazilian supercentenarians also stand out. The number of Brazilian women in the top 15 longest-lived worldwide exceeds that of more populous and wealthier countries, including the United States.
Expanding the Research Agenda
The research effort extends beyond sequencing DNA. Scientists are developing cellular models from selected participants for functional experiments and multi-omics analyses. Rather than simply confirming findings from less diverse populations, the goal is to identify protective variants and biological mechanisms that may be specific to Brazil. These discoveries could inform precision medicine approaches that are globally relevant while better reflecting human diversity. In collaboration with Prof. Ana Maria Caetano de Faria from the Universidade Federal de Minas Gerais, the team will also examine the immune profiles of this cohort in greater detail.
The authors call on international longevity and genomics consortia to expand recruitment to include ancestrally diverse and admixed populations such as Brazil, or to provide funding for genomic, immunological, and long-term studies that advance science while promoting equity in global health research.
Resilience as the Core Message
Supercentenarians represent more than unusually long lives. They exemplify resistance, adaptability, and resilience, qualities that aging research must better understand if the goal is not just longer lifespans but healthier ones. Rather than simply enduring old age, these individuals appear to actively counter many biological features of aging, offering insights that could reshape how longevity is understood.
“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,” says Dr. Mayana Zatz, corresponding author and Professor at the University of São Paulo.
This Viewpoint brings together current knowledge on supercentenarian biology with insights from an exceptional Brazilian cohort. By integrating genomic, immune, and clinical findings, the authors present a compelling case for broadening longevity research beyond traditionally studied populations and reveal patterns that remain hidden in genetically homogeneous groups.
Reference: “Insights from Brazilian supercentenarians” by Mateus V. de Castro, Monize V.R. Silva, João Paulo L.F. Guilherme and Mayana Zatz, 6 January 2026, .