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Literature DB >> 8129854

Human aging is associated with various point mutations in tRNA genes of mitochondrial DNA.

C Münscher¹, J Müller-Höcker, B Kadenbach.

Abstract

In extraocular muscle tissue of elderly humans small amounts of point mutations in tRNA genes of mitochondrial DNA (mtDNA) were identified by point mutation-specific PCR. These mutations were not found in navel-string samples from newborns. While the mutations in tRNA(Leu(UUR)) (np 3243) and tRNA(Gly) (np 10006), previously identified in patients with MELAS and CIPO, respectively, were found in most elderly people, the mutations in tRNA(Ser(GCU)O (np 12246) and tRNA(Asn) (np 5692), identified in patients with CIPO and CPEO, respectively, were found only in two of 15 tissue samples from different individuals. The data suggest that some nucleotides of mtDNA represent "hot spots" for somatic mutations, which contribute to human aging.

Entities: Chemical Gene Species

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Year: 1993 PMID： 8129854 DOI： 10.1515/bchm3.1993.374.7-12.1099

Source DB: PubMed Journal: Biol Chem Hoppe Seyler ISSN： 0177-3593

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Cited

18 in total

1. The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method.

Authors: D G Murdock; N C Christacos; D C Wallace
Journal: Nucleic Acids Res Date: 2000-11-01 Impact factor: 16.971

Human aging is associated with various point mutations in tRNA genes of mitochondrial DNA.

1. The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method.

2. Mutations in mitochondrial DNA accumulate differentially in three different human tissues during ageing.

3. Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging.

Review 4. Free-radical-induced mutation vs redox regulation: costs and benefits of genes in organelles.

5. Cloning of neuronal mtDNA variants in cultured cells by synaptosome fusion with mtDNA-less cells.

6. Skewed segregation of the mtDNA nt 8993 (T-->G) mutation in human oocytes.

7. Human disease-associated mitochondrial mutations fixed in nonhuman primates.

8. Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle.

Review 9. Mitochondrial function as a determinant of life span.

10. A novel mitochondrial tRNA(Val) T1658C mutation identified in a CPEO family.