Observational study finds Brazil's genetic diversity linked to extreme longevity in centenarians — Evidence Review
Published in Genomic Psychiatry, by researchers from Human Genome and Stem Cell Research Center at the University of São Paulo
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Table of Contents
Brazil’s exceptional genetic diversity makes it a unique setting for studying extreme human longevity, according to a recent study of centenarians and supercentenarians; related research broadly supports the importance of population diversity and resilience factors in healthy aging. Most prior studies agree that Brazilian populations hold untapped genetic and biological information relevant to global aging research, as seen in the findings summarized by the Human Genome and Stem Cell Research Center at the University of São Paulo.
- The study’s focus on Brazil’s admixed population addresses a gap identified in genomic longevity research, where most large datasets lack sufficient representation of genetically diverse and admixed groups, a concern echoed in recent Brazilian genomic surveys that discovered millions of novel variants 1 8.
- Related studies confirm that Brazilian centenarians exhibit genetic and biological traits—such as efficient DNA repair and unique immune profiles—that are consistent with findings from international cohorts, indicating shared mechanisms of resilience but also population-specific protective factors 2 9 10 11.
- Research on healthy life expectancy and morbidity in Brazil highlights significant social and regional disparities, reinforcing the study’s emphasis on resilience in populations with limited healthcare access and the importance of considering environmental and socioeconomic contexts alongside genetic factors 3 4 5 6 7.
Study Overview and Key Findings
Extreme longevity remains one of the most intriguing and understudied areas in human biology, especially outside of Europe and East Asia. This new study highlights the scientific importance of Brazil’s unique population structure, shaped by centuries of migration and admixture, and examines a rare cohort of exceptionally long-lived individuals to identify genetic, immunological, and resilience-related contributors to healthy aging. The work is particularly timely as global populations age and questions about the interplay between genetics, environment, and health span become more urgent.
| Property | Value |
|---|---|
| Study Year | 2023 |
| Organization | Human Genome and Stem Cell Research Center at the University of São Paulo |
| Journal Name | Genomic Psychiatry |
| Authors | Dr. Mayana Zatz, Mateus Vidigal de Castro |
| Population | Centenarians and supercentenarians in Brazil |
| Sample Size | n=160 centenarians, 20 supercentenarians |
| Methods | Observational Study |
| Outcome | Genetic diversity, immune profiles, resilience factors |
| Results | Brazil has unique genetic diversity linked to extreme longevity. |
Literature Review: Related Studies
To contextualize these findings, we searched the Consensus database, which indexes over 200 million research papers. The following search queries were used to identify relevant literature:
- Brazil genetic diversity extreme longevity
- longevity factors in Brazilian populations
- centenarians health genetics Brazil
| Topic | Key Findings |
|---|---|
| How does genetic diversity in Brazil shape health and longevity research? | - Brazilian genomes show high diversity and millions of novel variants, many of which are absent from global databases 1 8. - Admixture and ancestry-related genetic variants may influence health, fertility, immune response, and metabolic traits, creating both opportunities and challenges for longevity research 1 8. |
| What genetic and biological factors are associated with extreme longevity? | - Genes such as FOXO3, HLA, and others related to immune function and DNA repair are associated with longevity in Brazilian and international cohorts 2 9 11 12. - Centenarians often display unique immune profiles, efficient protein maintenance, and resilience to age-related diseases, with some evidence of familial clustering of extreme longevity 9 10 11 12. |
| What are the patterns and challenges of healthy aging and life expectancy in Brazil? | - Life expectancy and healthy life expectancy have increased, but social and regional disparities persist, with poorer regions experiencing shorter, less healthy lives 3 4 5 6 7. - Chronic noncommunicable diseases and disabilities are leading causes of morbidity among older adults, and women live longer but with more years of poor health 5 6 7. |
| How do Brazilian findings inform global longevity and aging research? | - Including underrepresented populations, such as Brazilians, yields new insights and improves the accuracy of genetic and clinical resources for aging research 1 8. - Brazilian centenarian studies build on and complement international research by revealing both shared and population-specific factors in extreme longevity 9 10 11 12. |
How does genetic diversity in Brazil shape health and longevity research?
Brazil’s rich genetic mosaic, shaped by centuries of migration and admixture, presents both challenges and unique opportunities for aging research. The new study’s identification of millions of previously unknown variants in elderly Brazilians is consistent with recent large-scale genomic analyses, which emphasize the need for broader representation in global databases and the potential for population-specific insights.
- Large-scale genome sequencing in Brazil has revealed over 8 million novel variants, many of which are predicted to impact health and are not found in other populations 1 8.
- Admixture has resulted in an uneven distribution of ancestry-specific haplotypes, which may influence health traits such as immune response and metabolism 1.
- The inclusion of admixed and diverse populations can improve the imputation and interpretation of genetic variants for medical research 8.
- These findings support the current study’s argument that studying Brazilian supercentenarians can uncover protective factors invisible in more homogeneous cohorts 1 8.
What genetic and biological factors are associated with extreme longevity?
The current study’s focus on immune system resilience, protein maintenance, and familial clustering of longevity aligns with a growing body of evidence linking these traits to exceptional aging. International research also points to specific genetic variants—especially in genes related to DNA repair and immune regulation—as contributors to extreme longevity.
- The FOXO3 gene has been associated with longevity in Brazilian cohorts, especially among women with low triglyceride levels 2.
- DNA repair mechanisms and somatic mutation patterns are crucial for healthy aging, as shown in supercentenarian studies from Italy and other countries 9.
- Resilience, or the ability to withstand physiological stress, is a recurring theme in centenarian biology internationally and is also observed among Brazilian supercentenarians 10.
- Cognitively healthy centenarians are enriched for protective variants, particularly in immune and endolysosomal system genes 11.
- Whole-exome sequencing has not yet identified rare protein-altering variants with major effects, suggesting that longevity is polygenic and complex 12.
What are the patterns and challenges of healthy aging and life expectancy in Brazil?
While Brazil’s life expectancy has improved, significant inequalities remain, particularly among women and those in less wealthy regions. The new study’s observation that many supercentenarians thrived despite limited medical access is notable against a backdrop of health disparities and the growing burden of chronic disease.
- Life expectancy at birth has risen steadily, but the increase in healthy life expectancy has been smaller, meaning older adults spend more years living with disability or chronic illness 5 6 7.
- Marked regional disparities exist, with those in the North and Northeast experiencing shorter and less healthy lives compared to those in richer regions 5.
- Women live longer than men but are expected to spend more years in poor health, regardless of the health metric used 6.
- Effective health programs for older adults require targeted interventions, primary care coordination, and support for informal caregivers, especially in underserved areas 3 4.
How do Brazilian findings inform global longevity and aging research?
The inclusion of genetically diverse and underrepresented populations, such as those in Brazil, is increasingly recognized as crucial for the advancement of aging research. The current study’s call for international collaboration and resource sharing echoes trends in the broader scientific community.
- Genomic studies in Brazil have contributed new variants and improved the accuracy of genetic reference panels for medical and aging research worldwide 1 8.
- Brazilian research complements international studies by identifying both shared and unique biological mechanisms of resilience and longevity 9 10 11 12.
- There is growing consensus that global consortia should prioritize diversity and equity in study recruitment to ensure findings are widely applicable 1 8.
- The new study’s multi-omics and functional approach may reveal additional protective pathways relevant across diverse populations.
Future Research Questions
While the current study advances understanding of extreme longevity in Brazil, many questions remain about the interplay of genetics, environment, and resilience. Future research is needed to clarify the mechanisms of healthy aging, identify population-specific protective factors, and ensure findings benefit diverse communities worldwide.
| Research Question | Relevance |
|---|---|
| What genetic variants are unique to Brazilian supercentenarians and linked to resilience? | Discovering population-specific variants could reveal new biological pathways of healthy aging and inform precision medicine approaches 1 8. |
| How do immune profiles of Brazilian supercentenarians differ from other populations? | Comparative studies may identify unique adaptive or protective immune features that contribute to extreme longevity, building on findings of unusual T-cell populations and strong viral responses 9 11. |
| What role do environmental and socioeconomic factors play in Brazilian longevity? | Understanding the interaction between genetics and environment is critical, especially given regional disparities in health and healthcare access 3 5 6 7. |
| Can multi-omics analyses identify novel protective mechanisms in admixed populations? | Integrating genomics, proteomics, and metabolomics may uncover mechanisms not apparent from genetic studies alone, especially in highly admixed groups 1 8. |
| How can findings from Brazilian centenarians inform global precision medicine? | Applying insights from diverse populations may improve the inclusivity and effectiveness of interventions for aging and age-related diseases worldwide 1 8 10. |