USP Genetic Research Reveals Secrets of Extreme Longevity in Brazilian Supercentenarians

Breakthrough in Longevity Research from Universidade de São Paulo

Brazilian researchers at the forefront of genetics have made headlines with a groundbreaking study on supercentenarians—individuals verified to have lived past their 110th birthday. Published on January 6, 2026, in the journal Genomic Psychiatry, the paper titled "Insights from Brazilian supercentenarians" sheds light on the genetic and immunological factors enabling extreme longevity in Brazil's diverse population. 72 73 Led by renowned geneticist Dr. Mayana Zatz from the Human Genome and Stem Cell Research Center (CEGH-CEL) at the University of São Paulo (USP)—Brazil's premier public university—the study analyzes data from over 160 centenarians, including 20 validated supercentenarians. This research positions USP as a global leader in aging science, attracting international attention to Brazilian higher education institutions. 70

The team's work challenges conventional views on aging, suggesting that Brazil's unique genetic admixture—stemming from European, African, Indigenous, and Asian ancestries—harbors protective variants overlooked in studies of more homogeneous populations like those in Europe or East Asia. With Brazil boasting three of the world's ten longest-lived validated males and numerous female supercentenarians ranking in the global top 15, the country emerges as a 'genetic treasure trove' for longevity research. 71

Defining Supercentenarians and Brazil's Exceptional Cases

Supercentenarians represent the pinnacle of human longevity, with fewer than 1 in 1,000 centenarians reaching this milestone. In Brazil, despite uneven healthcare access, the nation has at least 14 to 17 living supercentenarians as of late 2025, according to groups like LongeviQuest. Notable examples include Andrelino Vieira da Silva, born February 3, 1901 (aged 124 as of early 2026), from Bahia, and Sebastião Batista dos Santos, born March 15, 1902 (aged 123), highlighting clusters in regions like the Northeast. 10

Historical figures like Sister Inah Canabarro Lucas, who lived to 116 until her passing in April 2025, and the world's oldest living man (born 1912, aged 113+), underscore Brazil's prominence. A remarkable familial cluster features a 110-year-old woman whose nieces are aged 100, 104, and 106—the latter a South American swimming champion who took up the sport after 70. These cases, often from underserved rural areas, defy expectations tied to diet or medicine, pointing to innate biological resilience. 72

The DNA Longevo Project: Methods and Cohort Details

Launched in 2017, the DNA Longevo project at USP's CEGH-CEL recruits volunteers over 95, prioritizing supercentenarians via email (dnalongevo@usp.br). The cohort spans Brazil's regions, capturing social, cultural, and environmental diversity. Researchers collect clinical data, blood samples for genomic sequencing, and cellular analyses. Over 1,000 Brazilians aged 60+ yielded 2 million novel variants, 2,000+ mobile element insertions, and 140+ unique HLA alleles absent from global databases—totaling over 8 million undescribed variants, including 36,000 potentially deleterious ones. 73

Step-by-step, the process involves: 1) Validation of age via documents; 2) Whole-genome sequencing; 3) Multi-omics integration (genomics, transcriptomics, proteomics); 4) Cellular assays for proteasome activity, autophagy, and immune profiling; 5) Longitudinal tracking. Collaborations, like with Prof. Ana Maria Caetano Faria at Universidade Federal de Minas Gerais (UFMG), enhance immunological insights. This rigorous methodology ensures robust, reproducible findings. 70

• Preserved proteasomal activity in lymphocytes akin to youth.
• Upregulated autophagy for protein clearance.
• Expanded cytotoxic CD4+ T cells mimicking CD8+ profiles.

Genetic Variants: The Role of Brazil's Miscigenação

Miscigenação—or genetic admixture—defines Brazil's population, formed by Portuguese colonization, African enslavement (nearly 4 million arrivals), European/Japanese immigration, and Indigenous roots. This melting pot yields variants invisible in uniform cohorts. The study flags rare alleles in immune genes like HLA-DQB1, HLA-DRB5 (major histocompatibility complex for antigen presentation), and IL7R (interleukin-7 receptor for T-cell survival). Additional hits involve proteostasis (protein homeostasis) and genomic stability genes. 71

Dr. Mateus Vidigal de Castro, first author, notes: "Some genes replicate European findings, but new variants emerge from miscigenação, cataloged uniquely here." 73 Compared to a 116-year-old from a less admixed background, Brazilian cases show no strict diets—chocolate-loving nuns thrived—emphasizing genetics over lifestyle.

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Immune Resilience: Beyond Conventional Aging Theories

Traditional views depict immune senescence as decline, but USP data reframes it as adaptation. Supercentenarians' peripheral blood lymphocytes maintain youthful proteasome function—degrading damaged proteins—and enhanced autophagy, clearing cellular debris. CD4+ T cells expand with cytotoxic traits usually CD8-exclusive, bolstering defense. 72

Hormonal regulation persists unusually: sex hormones remain elevated, sustaining cellular vitality. Dr. João Paulo Limongi França Guilherme explains: "Cells appear younger, more resistant—decline doesn't occur as expected." This resilience shines in real-world tests.

Supercentenarians' Triumph Over COVID-19

In 2020, pre-vaccines, three supercentenarians contracted SARS-CoV-2 yet recovered fully. Assays revealed robust IgG/neutralizing antibodies and innate immune markers (plasma proteins, metabolites). This innate prowess, untethered to vaccination, underscores genetic fortification—vital amid Brazil's pandemic challenges. 71

Timeline: Infection during peak waves; rapid antibody surge; full recovery without hospitalization. Such cases validate the cohort's value for infectious disease resilience studies.

Familial Patterns and Polygenic Inheritance

Longevity clusters familially: centenarian siblings are 5-17 times likelier to reach 100. The 110-year-old with centenarian nieces exemplifies polygenic traits—multiple genes interacting. USP's biobank dissects genetic vs. epigenetic factors, aiding heritability models. 72

• Shared environments minimized by geographic spread.
• Heritability estimates: 20-30% genetic.
• Implications for GWAS (genome-wide association studies).

Implications for Global Medicine and Higher Education

Brazil's findings advocate inclusive genomics: diverse cohorts prevent biased therapies. Potential: precision medicine targeting proteostasis/autophagy drugs for healthy aging. Dr. Zatz urges international funding: "Brazil fills critical gaps." 70

In higher education, USP/UFMG lead; students/researchers flock to longevity labs. Interested? Visit academic CV tips or research assistant jobs. For Brazilian opportunities, see Brazil university jobs.

Future Directions and Calls to Action

Ongoing: 5-year sample expansion, immune deep-dives, functional variant tests. Global consortia sought for equity. Brazil's 37,000+ centenarians (2022 Census) fuel this. 73

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