title: mtLOH (mitochondrial loss of heteroplasmy), aging, and 'surrogate self'.
abstract: In tribute to Dr Strehler, an attempt is made to use a style of reasoning found in some of his later papers as an outline of this article. First, general arguments in favor of the involvement of somatic mutations in mtDNA in the aging process are presented. Second, evidence is provided in support of a general tendency of mitochondrial genomes to reach homoplasmic state at the cellular level, for which we propose the term mitochondrial loss of heteroplasmy (mtLOH). This process is likely to facilitate the involvement of mtDNA mutations in the aging process by streamlining the phenotypic expression of the mutant genotype. Third, preliminary evidence of the very high incidence of clonal deletions in pigmented neurons of substantia nigra is reported. This observation highlights the possibility that accumulation of mtDNA mutations specific in certain cell types of a complex tissue may account for the involvement of mtDNA mutations in the aging process despite the relatively low average incidence of these mutations in the tissue as a whole. High incidence of mtDNA deletions in pigmented neurons evokes Strehler's idea that efforts to delay aging may not be the most cost-efficient way of preserving 'self awareness and a joyful sense of life', as he put it. A potential alternative suggested by Strehler, i.e. creation of a 'surrogate self' by computer simulation may deserve more attention than it currently enjoys.
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Rm. 921, 77 Ave. L. Pasteur, Boston, MA 02115, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Nekhaeva
authors.forename: Yevgenya
authors.initials: Y
authors.lastname: Kraytsberg
authors.forename: Konstantin
authors.initials: K
authors.lastname: Khrapko
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria
chemical_list: D004272:DNA, Mitochondrial