People who regularly read my blog will know my hypothesis that ageing results primarily from damage to mitochondrial DNA. Details of this can be found here. A question that arises, of course, is given that the laws of chemistry and physics are the same why do different species have different average lifespans. Obviously there are quite a few things that could make a difference. The process of autophagy matters and in which circumstances that happens, but also there are enzymes that are available in the mitochondrion that repair damaged mtDNA.
One of these enzymes is OGG1. Interestingly this enzyme is not available for C. Elegans. Nor is MUTYH which gives a second chance to fix errors that OGG1 has failed to fix. More details about this are available here.
Unsurprisingly a large amount of unrepaired lesions (where damage is caused to mtDNA) appear in older C. Elegans and it has a relatively short life.
Mitochondrial base excision repair positively correlates with longevity in the liver and heart of mammals is a paper that then looked more generally at mammals. It says "Our results show, for the first time, a positive correlation between (mitochondrial) BER and mammalian longevity. ", but also "However, previous studies showed that repair of endogenous damage to nuclear DNA (base excision repair, BER) is negatively or not correlated with mammalian longevity. " There is not much I can add to this and obviously the paper is available to be read.
Repair of mtDNA is not the only thing that influences lifespan. Another thing that has such effects is the question of how vulnerable the mtDNA is to oxidative damage. In that we have the Hydra which at times is immortal. The thing to note about the Hydra is that it only has two tRNAs in the mtDNA genome when normally there are 22. As most pathological mtDNA mutations - which cause a lot to fail based upon just one mutation - are mutations to the tRNA the Hydra is likely to suffer fewer catastropic mutations when damage happens to the mtDNA.
Obviously selective mitophagy that clears the lower quality mitochondria along with their mtDNA is also important. However, at lot is explained by the two items above.
One of these enzymes is OGG1. Interestingly this enzyme is not available for C. Elegans. Nor is MUTYH which gives a second chance to fix errors that OGG1 has failed to fix. More details about this are available here.
Unsurprisingly a large amount of unrepaired lesions (where damage is caused to mtDNA) appear in older C. Elegans and it has a relatively short life.
Mitochondrial base excision repair positively correlates with longevity in the liver and heart of mammals is a paper that then looked more generally at mammals. It says "Our results show, for the first time, a positive correlation between (mitochondrial) BER and mammalian longevity. ", but also "However, previous studies showed that repair of endogenous damage to nuclear DNA (base excision repair, BER) is negatively or not correlated with mammalian longevity. " There is not much I can add to this and obviously the paper is available to be read.
Repair of mtDNA is not the only thing that influences lifespan. Another thing that has such effects is the question of how vulnerable the mtDNA is to oxidative damage. In that we have the Hydra which at times is immortal. The thing to note about the Hydra is that it only has two tRNAs in the mtDNA genome when normally there are 22. As most pathological mtDNA mutations - which cause a lot to fail based upon just one mutation - are mutations to the tRNA the Hydra is likely to suffer fewer catastropic mutations when damage happens to the mtDNA.
Obviously selective mitophagy that clears the lower quality mitochondria along with their mtDNA is also important. However, at lot is explained by the two items above.
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