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Mitochondrial and nuclear DNA mismatch may impact ageing

11 July 2016

By Dr Julia Hill

Appeared in BioNews 859

The interaction between mitochondrial and nuclear DNA may have implications for health, metabolism and ageing, according to a new study.

The findings, which were published in Nature, could inform how the recently approved technique of mitochondrial donation is performed (see BioNews 792).

'The key to this study was understanding how the combination and interaction of our two genomes – the nuclear and the mitochondrial – triggers a cellular adaptation with repercussions throughout our lives,' said Dr Ana Latorre-Pellicer of the University of Santiago de Compostela and the first author of the paper. 

The researchers created mice with 'matched' and 'mismatched' nuclear and mitochondrial DNA (mtDNA) from two strains of mice. The new strains of mice were created through 20 generations of selective breeding. The two 'parent' strains had mitochondrial differences approximately equivalent to those between the mtDNA of African and Eurasian people. 

The mice with mismatched mtDNA and nuclear DNA appeared to be healthier and age better. They had a longer median lifespan than the wild-type mice (although their maximum lifespan was not different) and their telomeres shortened at slower rate, which suggests they age more slowly. They had lower incidence of tumours, lower cholesterol, and they did not experience the age-related decline in respiration that was seen in wild-type mice. They also gained less weight than controls, despite having the same diet, and their blood-insulin levels fluctuated less after fasting, suggesting they were more resistant to diabetes.

Despite these positive signs of health, the mismatched animals also had a higher level of reactive oxygen species at a young age, which is normally associated with cellular damage.

'What they are seeing in the mismatched cases is basically an increase in oxidative stress, and that appears to be having generally a beneficial effect on health,' evolutionary biochemist Dr Nick Lane of University College London, who was not involved in the study, told The Scientist.

Dr Lane suggested that the mismatch could cause a cell to experience mild stress. 'A mild stress response, as long as it's not too much, might be good for your overall health,' he explained. This process is known as hormesis.

If these findings translate to humans, then they could have implications for mitochondrial donation – an IVF technique to prevent the transmission of mitochondrial disease from mother to child. In the process, nuclear DNA from the mother is inserted into a donor egg (from which the nuclear material has been previously removed), which is then fertilised.

Despite the fact that this new work indicates beneficial effects on health caused by such mismatching, Professor Doug Turnbull of the University of Newcastle, who has pioneered the technique of mitochondrial donation, still suggests that donors and recipients be closely matched. He told The Economist that the research was done in highly in-bred mice and therefore needs corroboration, and for now all that we know is that mismatching can have 'profound effects'.

The Scientist | 06 July 2016
Science Daily (press release) | 06 July 2016
Nature | 06 July 2016
The Economist | 09 July 2016


27 March 2017 - by Dr Linda Wijlaars 
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16 January 2017 - by Matthew Thomas 
Is ageing inevitable, or can it be stopped? The Guardian Science Weekly podcast explored the latest thinking in the science of ageing...
19 December 2016 - by Sarah Gregory 
Gene therapy can reverse the effects of ageing in mice, researchers claim...
05 December 2016 - by Dr Julia Hill 
Scientists advising the HFEA have recommended that the technique of mitochondrial replacement therapy be approved for clinical use in the UK...
31 October 2016 - by Georgia Everett 
Seventeen children conceived through ooplasmic transplantation have all matured with regular health and cognitive abilities, according to a study...

04 July 2016 - by Dr Katie Howe 
Researchers have identified a gene that, when activated, causes mitochondria inherited from sperm to be destroyed shortly after fertilisation...
13 June 2016 - by Dr Özge Özkaya 
An extensive study examining human embryos created using mitochondrial donation has demonstrated that the technique does not adversely affect embryo development...
23 May 2016 - by Dr Rosie Gilchrist 
A study has identified a potential problem with mitochondrial donation, an IVF technique that aims to prevent the transmission of faulty mitochondria from mother to child...
25 April 2016 - by Dr Julia Hill 
A study has found that stem cells from older people accumulate high numbers of mitochondrial DNA mutations, which could limit their therapeutic value...
15 February 2016 - by Dr Peter Mills 
The US NAS has published a report on the ethical, social and policy considerations relating to mitochondrial replacement techniques. The recommendation that has inevitably attracted most attention, however, is that only male embryos should be transferred, an approach that was considered but rejected in the UK...

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