Genetic 鈥減arasites鈥� known as retrotransposons become more active in all kinds of animals as they age, and this increased activity shortens lifespans. Now, an animal study has shown this ageing effect isn鈥檛 a result of mutations to the genome as previously thought, but could be a result of the parasite activity triggering an immune response.
Understanding exactly how these chunks of parasitic DNA shorten lifespans could lead to ways to extend human lives. 鈥淏ut this is very far down the road,鈥� says Blair Schneider at the Albert Einstein College of Medicine in New York.
The genomes of all animals are infested with retrotransposons, which are bits of DNA that can copy and paste themselves into other parts of the genome. The human genome, for instance, contains 100,000 copies of a retrotransposon called LINE1, although many of these copies have degenerated and can no longer copy and paste themselves.
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Having a genetic parasite insert copies of itself into random places in the genome is dangerous, as this can disrupt key genes and even trigger cancer. So cells have mechanisms for suppressing the activity of retrotransposons 鈥� that is, for stopping their DNA being transcribed into RNA, the first step in the copying process.
As animals age, however, these mechanisms start to fail and retrotransposons become more active. Numerous studies have shown that this , from rheumatoid arthritis to Alzheimer鈥檚, and that suppressing this activity can extend the lifespan of animals such as mice.
The obvious explanation is that as retrotransposons become active, they generate lots of harmful mutations by pasting copies of themselves into the genome. To find out how many mutations accumulate, Schneider and her colleagues sequenced the genomes of individual cells from young and old fruit flies (Drosophila melanogaster) so they could directly measure the number of new insertions. Their study is the first to look at this at the level of individual cells.
To their surprise, there was no significant increase in retrotransposon insertions in the cells from old flies. 鈥淲hich we didn鈥檛 believe to start with,鈥� says team member , also at the Albert Einstein College. 鈥淭his makes no sense 鈥� of course there are new integrations, but there just aren鈥檛.鈥�
The team only looked at a few tissue types because of the difficulty in analysing single cells. But Schneider says she is aware of another team finding similar results in human cells, in as-yet unpublished work.
Despite the lack of new insertions, the results add to the evidence that retrotransposon activity reduces lifespan. When the team suppressed the activity of just one retrotransposon, it extended the lifespan of the flies by nearly 10 per cent.
The researchers saw a similar lifespan extension when they used a different method and when they suppressed a different retrotransposon. 鈥淲e鈥檙e pretty confident that it is to do with the transposon expression itself,鈥� says Schneider.
So what鈥檚 going on? 鈥淭he short answer is, we are not really sure,鈥� she says. But the team did find an increase in the activity of genes linked to the immune system.
What may be happening is that cells are mistaking retrotransposon activity for a viral infection and triggering immune responses that lead to persistent inflammation. And persistent inflammation is thought to be one of the causes of ageing.
鈥淚t鈥檚 a very interesting study,鈥� says at the Rochester Aging Research Center in New York. 鈥淚t supports the concept that transposons affect ageing mostly by inducing inflammation rather than by inducing mutations.鈥�
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