Why Studying Extreme Longevity Matters
Why do a handful of people live well past 110 years while most never reach 100? Despite decades of research, the biology of extreme longevity remains only partially understood. According to a Viewpoint published on January 6 in Genomic Psychiatry, the problem may not be a lack of data—but a lack of diversity in that data.
Led by Dr. Mayana Zatz and researchers from the Human Genome and Stem Cell Research Center at the University of São Paulo, the study argues that longevity science has largely overlooked populations with complex genetic ancestry. This gap is particularly limiting when studying supercentenarians, individuals whose biology may reveal protective mechanisms invisible in homogeneous populations.
Brazil: An Overlooked Longevity Research Powerhouse
Brazil’s Unmatched Genetic Diversity
Brazil’s population history is unlike that of almost any other nation. Portuguese colonization beginning in 1500, the forced migration of nearly 4 million enslaved Africans, and later immigration from Europe and Japan created one of the most genetically diverse populations in the world.
Early genomic studies of more than 1,000 Brazilians over age 60 uncovered nearly 2 million previously unknown genetic variants. Among older adults alone, researchers identified over 2,000 mobile element insertions and 140 HLA alleles absent from global genomic databases. Subsequent research expanded this number to more than 8 million undescribed variants, including tens of thousands with potential functional significance.
This diversity makes Brazil a uniquely powerful natural laboratory for understanding how genetics influences human lifespan.
A Rare Cohort of Supercentenarians
The Brazilian research team has assembled one of the world’s most valuable longevity cohorts. Their ongoing longitudinal study includes more than 160 centenarians, among them 20 validated supercentenarians from diverse regions, cultures, and socioeconomic backgrounds.
Notable participants include Sister Inah, recognized as the world’s oldest living person until her death in April 2025 at age 116. The cohort has also included the two oldest men in the world, one currently aged 113.
Living Beyond Medical Advantage
What makes this cohort extraordinary is not just age, but resilience. Many participants spent most of their lives in underserved areas with minimal access to modern healthcare. When first evaluated, several were still cognitively sharp and capable of managing daily activities independently.
This allows scientists to study biological resilience that evolved largely without medical intervention, offering rare insight into natural protective mechanisms against aging.
Families That Defy Aging Odds
One family in the study illustrates inherited longevity at its most striking. A 110-year-old woman has nieces aged 100, 104, and 106, making it one of Brazil’s longest-lived documented families. Remarkably, the oldest niece was still a competitive swimmer at age 100.
Previous studies show siblings of centenarians are 5 to 17 times more likely to reach extreme old age themselves. These families may help researchers untangle genetic, epigenetic, and environmental contributions to longevity.
What Makes Supercentenarians Biologically Unique
Recent studies reveal that supercentenarians are not simply aging more slowly—they are aging differently.
Their immune cells maintain efficient protein recycling systems, similar to those of much younger individuals. Cellular cleanup processes remain active, preventing the accumulation of damaged proteins. Single-cell analyses show an unusual expansion of cytotoxic CD4+ T cells, a profile rarely seen in younger populations.
A multi-omics study of a 116-year-old supercentenarian identified rare variants in immune-related genes such as HLA-DQB1, HLA-DRB5, and IL7R, along with genes tied to genome stability. Unlike some long-lived populations, Brazilian supercentenarians report no consistent dietary restriction, suggesting multiple biological pathways to longevity.
COVID-19 Survival at Extreme Old Age
During the COVID-19 pandemic, resilience was tested in real time. Three Brazilian supercentenarians survived SARS-CoV-2 infection in 2020, before vaccines were available.
Laboratory analyses revealed strong IgG responses, neutralizing antibodies, and immune metabolites linked to early viral defense. How individuals over 110 mounted such effective immune responses remains a critical research question.
Brazil’s Global Standing in Longevity Science
Brazil accounts for three of the ten longest-lived validated male supercentenarians worldwide, including the oldest living man born in 1912. This is especially notable given the rarity of extreme longevity among men.
Brazilian women also rank prominently, with more women in the global top 15 longest-lived than many wealthier and more populous nations.
The Future of Longevity Research
Researchers are now moving beyond DNA sequencing to cellular models, functional experiments, and multi-omics analyses. Collaborations with immunology experts aim to deepen understanding of resilience mechanisms that could inform precision medicine globally.
The authors urge international consortia to include ancestrally diverse and admixed populations, promoting both scientific discovery and equity in global health research.
Resilience, Not Decline, as the Core Insight
Supercentenarians are not merely surviving old age—they are actively resisting it. Their biology reflects adaptation, stability, and resilience rather than inevitable decline.
By integrating genomic, immune, and clinical insights from Brazil’s diverse population, this research reveals aging as a modifiable biological process, offering lessons that could improve healthspan for future generations.
