Of late researchers have been investigating a possible role for transposable elements, or transposons, in degenerative aging. These are DNA sequences that can move around in the genome, and the incidence of such movement increases with age. This fits in with the general consensus that stochastic mutation of nuclear DNA is a cause of aging, through disarray of normal cellular operations. This view is disputed in some quarters by the suggestion that outside of cancer risk the effect isn't significant over the present human life span in comparison to other forms of damage. In the case of transposons, whether it is a cause or consequence of other age-related changes in cellular biology is still up for debate. The work here adds a little more to the evidence already in hand:
A new study increases and strengthens the links that have led scientists to propose the "transposon theory of aging." Transposons are rogue elements of DNA that break free in aging cells and rewrite themselves elsewhere in the genome, potentially creating lifespan-shortening chaos in the genetic makeups of tissues. As cells get older, prior studies have shown, tightly wound heterochromatin wrapping that typically imprisons transposons becomes looser, allowing them to slip out of their positions in chromosomes and move to new ones, disrupting normal cell function. Meanwhile, scientists have shown that potentially related interventions, such as restricting calories or manipulating certain genes, can demonstrably lengthen lifespans in laboratory animals. "In this report the big step forward is towards the possibility of a true causal relationship. So far there have been associations and suggestions that to all of us make sense, but you need the data to back up your opinion."
In one set of experiments, the team visually caught transposable elements in the act of jumping around in fruit flies as they aged. They inserted special genetic snippets into fat body cells, the equivalent of human liver and fat cells in flies that would glow bright green when specific transposable elements move about in the genome. Under the microscope the scientists could see a clear pattern of how the glowing "traps" lit up more and more as the flies aged. The increase in transposon activity was not steady as flies grew older. The data show that the timeframe in which transposable element activity really begins to increase is tightly correlated with the time when the flies start to die. Several experiments in the paper also show that that a key intervention already known to increase lifespan, a low-calorie diet, dramatically delays the onset of increased transposon activity.
To further explore the connection between transposon expression and lifespan, the team tested the effects of manipulating genes known to improve heterochromatin repression that are not only found in flies, but also in mammals. For example, increasing expression of the gene Su(var)3-9, which helps form heterochromatin, extended maximal fly lifespan from 60 to 80 days. Increasing expression of a gene called Dicer-2, which uses the small RNA pathway to suppress transposons, added significantly to lifespan as well. For all the new results, the researchers say it's still not quite time to declare outright that transposons are a cause of aging's health effects. But new experiments are planned. For example, the team will purposely encourage expression of transposable elements to see if that undermines health and lifespan. Another approach could be to use the powerful CRISPR gene editing technique to specifically disable the ability of transposable elements to mobilize within the genome. If that intervention affected lifespan, it would be telling as well.