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Genetic associations with longevity in a Calabrian cohort: an exploratory genome-wide study
Livia Beccacece1, Paolina Crocco2, Benedetta Torbidoni-Baldassari1
1Genomic And Molecular Epidemiology (GAME) Lab., School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Italy.
Geroscience
|May 23, 2026
Summary
Investigating genetic factors in Calabrian centenarians revealed unique influences on longevity. A genome-wide association study identified a significant locus, highlighting proteasome gene regulation as a key mechanism for extreme survival.
Area of Science:
- Genetics
- Gerontology
- Population Studies
Background:
- Human longevity is a complex trait influenced by genetics and environment.
- Calabria, Italy, has a high prevalence of centenarians and genetic isolation, making it ideal for longevity research.
Purpose of the Study:
- To investigate the genetic architecture of extreme human survival in the Calabrian population.
- To identify genetic variants associated with longevity in this unique cohort.
Main Methods:
- Genome-wide association study (GWAS) on 705 Calabrian individuals.
- Comparison of long-lived subjects with younger controls using a mixed-model approach.
- Meta-analysis for replication and validation of identified loci.
Main Results:
- Identified 22 suggestive longevity risk loci, with one reaching genome-wide significance.
- Confirmed an intronic variant regulating proteasome-related gene expression via meta-analysis.
- Observed no association with established longevity genes like APOE and FOXO3, suggesting population-specific effects.
Conclusions:
- Longevity in Calabrian individuals is influenced by a combination of unique genetic factors and conserved aging mechanisms.
- Proteostasis, genome integrity, apoptosis, and insulin/inflammation pathways are potentially involved in Calabrian longevity.
- Findings provide insights into the molecular basis of human lifespan extension and highlight population-specific genetic influences.
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