Mitochondrial DNA polymorphisms associated with longevity in the Turkish population

Area of Science:

• Genetics
• Gerontology
• Molecular Biology

Background:

• Mitochondrial DNA (mtDNA) mutations are implicated in aging and age-related diseases.
• Some mtDNA mutations may confer longevity benefits by reducing oxidative stress.

Purpose of the Study:

• To investigate aging-related variations in the entire mitochondrial genome within the Turkish population.
• To identify specific mtDNA mutations and haplotypes associated with longevity.

Main Methods:

• Whole mitochondrial DNA re-sequencing of 50 individuals (nonagenarians and controls).
• Comparative analysis of single nucleotide polymorphism (SNP) frequencies, SNP effects, SNP accumulation in mtDNA regions, and haplotype profiles.
• Statistical evaluation of observed variations between elderly and control groups.

Main Results:

• Significantly higher total mitochondrial SNP frequency in nonagenarians compared to controls.
• Increased prevalence of non-coding, synonymous, and tRNA mutations in the 90+ group.
• Specific polymorphisms (A73G, C152T) associated with longevity; a novel ATPase6 gene transversion (C8899A) negatively associated with longevity.
• Accumulation of mutations in the D-loop region and Complex I genes; increased non-synonymous mutations in Complex I genes in aged subjects.
• Haplotype H was more prevalent in the control group.

Conclusions:

• Mitochondrial genome variations play a role in human longevity.
• The functionality of oxidative phosphorylation is linked to aging and lifespan.
• This study provides the first comprehensive whole mtDNA sequencing for the Turkish population.