Human genomicsOct 8, 2025

Genetic patterns linked to exceptional long life in people over 100 years old

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 19, 2026

Abstract

Common genetic variations were identified among 21 individuals aged 110 years or older, with 754,520 SNPs shared across the samples.

11,348 coding variants were annotated, with 4,980 identified as non-synonymous.
110 of the non-synonymous variants are associated with deleterious effects linked to 79 genes.
16 novel variants were identified in 9 genes among the deleterious SNPs.
A subset of the common, non-synonymous SNPs had minor allele frequencies below 1%, suggesting they may be rare variants specific to this cohort.
148 enriched biological pathways were identified, including those related to extracellular matrix remodeling and metabolism.

Simplified

Aging, a complex biological process, entails sequential changes in organisms that elevate the risk of frailty, disease, and mortality, affecting individuals at the level of cellular, organ, and organism. This process is influenced by genetic diversity, socioeconomic status, healthcare infrastructure, lifestyle choices, and cultural practices. Gerontology delves into the factors shaping longevity, aging processes, and aging from both evolutionary and individual perspectives. and serve as models for studying exceptional longevity, offering insights into the aging process and resistance to age-related diseases. This research investigates common genetic variations (SNPs) shared among 3 centenarians and 18 supercentenarians, individuals aged 110 years or older. 754,520 SNPs were found to be common among all the 21 samples. Utilizing SNPnexus, a genetic variant annotation tool, we annotated coding variants and assessed potential disease susceptibilities associated with these variants. Ensembl was used as an annotation system, we annotated 1,607,122 variants, and found 11,348 coding variants. Among them, 4980 had non-synonymous variants, and 110 variants were observed to have deleterious effects. These deleterious SNPs were linked with 79 genes among them 16 novel variants were identified in 9 genes. The population frequency comparison using the 1000 Genomes Project and gnomAD revealed that a subset of these common, non-synonymous SNPs and deleterious SNPs had minor allele frequencies (MAF) below 1% or were absent entirely, suggesting potential rare variants specific to this cohort. In addition, we also found statistically significant (p < 0.05) 148 enriched pathways, among them the top enriched pathways such as extracellular matrix (ECM) remodeling, signal transduction, disease-associated pathways, sensory processing and metabolism of proteins and RNA. These preliminary findings may help prioritize candidate variants and genes for future studies on larger cohorts with appropriate controls can help in understanding the genetic basis of exceptional longevity.

Key numbers

754520

Common Identified

Total common found in 21 individuals aged 106 to 117 years.

110

Deleterious

Total deleterious associated with 79 genes.

148

Enriched Pathways

Statistically significant enriched pathways identified in the study.

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Genetic patterns linked to exceptional long life in people over 100 years old

Abstract

Key numbers

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