QUANTITATION OF AGE-RELATED MITOCHONDRIAL-DNA DELETIONS IN RAT-TISSUES SHOWS THAT THEIR PATTERN OF ACCUMULATION DIFFERS FROM THAT OF HUMANS

Three age-related mtDNA deletions were identified, and the competitive polymerase chain reaction (PCR) was used to quantitate their levels i n different Fisher 344 rat tissues. Deletions that removed 4834; 13273 ; or 13415 nt of the mitochondrial genome were shown to be associated with 16 (mtDNA(4834)), nine (mtDNA(13273)), or five (mtDNA(13415)) nt direct repeats, respectively. The mtDNA(4834) deletion was detected in an age-related manner in all tissues screened; the mtDNA(13415) delet ion was detected in old heart, and in both young and old brain; and th e mtDNA(13273) deletion was only detected in old brain tissues. The mt DNA(4834) deletion was found to be at its highest level in the liver ( 1.88 x 10(-2)%), followed by the brain (0.22 x 10(-2)%) and kidney (0. 40 x 10(-2)%) of old animals. Much lower levels were observed in old h eart (0.07 x 10(-2)%) and lung (0.04 x 10(-2)%). This distribution of mtDNA deletions in old rat tissues is in contrast to work done in huma ns where age-related deletions are present at the highest levels in po st-mitotic tissues with much lower levels in more mitotic tissues. An inverse relationship was observed between the level of mtDNA deletions and the size of the deleted region, since the mtDNA(13415) deletion w as present at about a 100-fold lower level (0.53 x 10(-5)%) than the s maller mtDNA(4834) deletion in old heart tissue. (C) 1998 Elsevier Sci ence B.V.