Transplanting Mitochondria

Friday, July 15th, 2016

Transplanting mitochondria extends life — in mice:

Dr Enríquez and his colleagues worked on that scientific stalwart, the mouse. Many genetic strains of lab mice are available, and the team started with two whose mitochondria had been shown by DNA analysis to have small but significant differences—about the same, Dr Enríquez reckons, as the ones between the mitochondria of modern Africans and those of Asians and Europeans, people whose ancestors left Africa about 60,000 years ago. They then copied the procedure for human mitochondrial transplants by removing fertilised nuclei from eggs of one strain, leaving behind that strain’s mitochondria, and transplanting them into enucleated eggs of the second strain, whose mitochondria remained in situ. A group of the first strain, left unmodified, was employed as a control. The researchers raised the mice and kept an eye on how they developed.

While the animals were young, few differences were apparent between modified and unmodified individuals. But as murine middle age approached, at around the animals’ first birthdays, differences began to manifest themselves. Modified mice gained less weight than controls, despite having the same diet. Their blood-insulin levels fluctuated less after fasting, suggesting they were more resistant to diabetes. Their muscles deteriorated less rapidly with age. And their telomeres—protective caps on the ends of their chromosomes whose shortening is implicated in ageing—stayed lengthier for longer.

Not all of the changes were beneficial. Young, unmodified mice had lower levels of free radicals—highly reactive (and therefore damaging) chemicals produced by mitochondria—than did their modified brethren, though even that difference reversed itself after the animals were 30 weeks old. But the combined result of the various changes was that the modified mice lived longer. Their median age at death was about a fifth higher than that of their unmodified cousins.

Given the fundamental metabolic role played by mitochondria, it makes sense that replacing one set with another, more distantly related set causes profound changes. The surprise is that those changes seem largely positive. Most biologists would have predicted the opposite, assuming that nuclear and mitochondrial DNA would co-evolve to interact optimally, so that mixing versions which have not co-evolved would be harmful.

Though unsure what to make of his discovery, Dr Enríquez suggests that a concept called hormesis might offer an explanation. This is the observation that a small amount of adversity can sometimes do an animal good, by activating cellular repair mechanisms that go on to clear up other damage which would otherwise have gone untreated. The biochemical cost of coping with mismatched mitochondria might, therefore, be tempering the animals’ metabolisms in ways that improve their overall health.

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