Quantitation of age-related mitochondrial DNA deletions in rat tissues shows that their pattern of accumulation differs from that of humans

Abstract

Three age-related mtDNA deletions were identified, and the competitive polymerase chain reaction (PCR) was used to quantitate their levels in different Fisher 344 rat tissues. Deletions that removed 4834; 13273; or 13415nt of the mitochondrial genome were shown to be associated with 16 (mtDNA4834), nine (mtDNA13273), or five (mtDNA13415) nt direct repeats, respectively. The mtDNA4834 deletion was detected in an age-related manner in all tissues screened; the mtDNA13415 deletion was detected in old heart, and in both young and old brain; and the mtDNA13273 deletion was only detected in old brain tissues. The mtDNA4834 deletion was found to be at its highest level in the liver (1.88x10-2%), followed by the brain (0.22x10-2%) and kidney (0.40x10-2%) of old animals. Much lower levels were observed in old heart (0.07x10-2%) and lung (0. 04x10-2%). This distribution of mtDNA deletions in old rat tissues is in contrast to work done in humans where age-related deletions are present at the highest levels in post-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 mtDNA13415 deletion was present at about a 100-fold lower level (0.53x10-5%) than the smaller mtDNA4834 deletion in old heart tissue.