Premature ageing in mice expressing defective mitochondrial DNA polymerase

Interestingness: 8

By Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlöf S, Oldfors A, Wibom R, Törnell J, Jacobs HT and Larsson NG, in Nature, on the 27th of May, 2004. 429(6990):417-23. http://www.ncbi.nlm.nih.gov/pubmed/15164064


This isn't a paper from Rejuvenation Research, but since it was referenced in the last post, I read it and found it very interesting, notwithstanding de Grey's comments on it not being as interesting as it seems.

They created mice with a mutant version of the mtDNA polymerase instead of the regular version, that resulted in 3-5 times the usual number of mutations in their mtDNA and many more mtDNA deletions (30% less full-length mtDNA than wild type).  Mutations were uniform throughout the whole mtDNA.  The method of creating these mutant mice is interesting enough, but I won't describe that here.

These mice live for about a year. They have much smaller testes by the 3 month mark. They then get some fucked-up looking back deformations (kyphosis), start losing their hair, losing weight, become anaemic (with larger than usual and paler red blood cells), and get enlarged spleens by around the six-month mark.  They develop osteoporosis and enlarged left ventricles at around the 9 month mark.

If de Grey's explanation is right then it's not significant, but if he is wrong, then mtDNA mutations become more important.