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Mitochondrial genotype associated with longevity and its inhibitory effect on mutagenesis
1Department of Gene Therapy, Gifu International Institute of Biotechnology, Yagi Memorial Park, Gifu, 505-0116, Mitake, Japan. tanakamx@infonia.ne.jp
Abstract:
Mitochondria are not only the major site of ATP production in cells but also an important source of reactive oxygen species (ROS) under certain pathological conditions. Because mitochondrial DNA (mtDNA) in the mitochondrial matrix is exposed to ROS that leak from the respiratory chain, this extranuclear genome is prone to mutations. Therefore, the mitochondrial genome is a rich source of single nucleotide polymorphisms (SNPs) and the functional significance of SNPs in the mitochondrial genome is comparable to that of SNPs in the entire nuclear genome. To demonstrate the contribution of mitochondrial SNPs to the susceptibility to adult-onset diseases, we analyzed the mtDNA from Japanese centenarians and identified a longevity-associated mitochondrial genotype, Mt5178A. Because this genotype was demonstrated to suppress the occurrence of mtDNA mutations in the oocytes, it also would seem to decelerate the accumulation of mtDNA mutations in the somatic cells with increasing age. This genotype is likely to confer resistance to adult-onset diseases by suppressing obesity and atherosclerosis.
Insights
Mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) influence adult-onset diseases. A specific mitochondrial genotype, Mt5178A, identified in centenarians, may confer longevity by reducing mtDNA mutations and suppressing obesity and atherosclerosis.
Area of Science:
- Genetics
- Cell Biology
- Gerontology
Background:
- Mitochondria are central to cellular energy production (ATP) and can generate reactive oxygen species (ROS).
- Mitochondrial DNA (mtDNA) is vulnerable to ROS-induced mutations due to its location within the mitochondrial matrix.
- Single nucleotide polymorphisms (SNPs) in mtDNA are significant for disease susceptibility, comparable to nuclear genome SNPs.
Purpose of the Study:
- To investigate the role of mitochondrial SNPs in susceptibility to adult-onset diseases.
- To identify longevity-associated mitochondrial genotypes in Japanese centenarians.
Main Methods:
- Analysis of mitochondrial DNA (mtDNA) from Japanese centenarian populations.
- Identification and characterization of specific mitochondrial genotypes.
Main Results:
- A longevity-associated mitochondrial genotype, Mt5178A, was identified.
- This genotype was shown to suppress the occurrence of mtDNA mutations in oocytes.
- The Mt5178A genotype may decelerate mtDNA mutation accumulation in somatic cells with age.
Conclusions:
- The Mt5178A mitochondrial genotype likely confers resistance to adult-onset diseases.
- This resistance may be mediated by the suppression of obesity and atherosclerosis.
- Mitochondrial SNPs play a crucial role in aging and age-related disease development.