Most of us accept that aging and eventually death are just the inevitable prices we pay for being alive in the first place – but maybe there's a way to skip out on the bill. Anti-aging research has long focused on DNA structures known as telomeres, which have been directly linked to cell longevity. Now scientists at Arizona State University have discovered a new way to potentially supercharge the mechanism, which may help keep this "molecular clock" – and by extension, ourselves – running better for longer.
Cell division is dictated by the genetic blueprints contained in chromosomes, which are X-shaped threads of DNA. The problem is, with each division a tiny piece of that information is lost, and eventually the chromosome degrades to the point where the cell can't divide anymore. In turn, this reduced cell growth shows itself in the body as the all-too-familiar degradation and disease that we associate with aging.
Telomeres are our natural defenses against this process. Made up of repeating sequences of DNA, these little caps sit on the end of each arm of the X-shape, and with each cell division they take the hit so that no important genetic information is lost. Unfortunately, they can't keep that up forever, and the march of time eventually wears them down. In that way, the length of our telomeres directly correlates to our lifespan and healthspan.
Realizing this relationship, scientists have for years been trying to find ways to slow down the degradation of telomeres, repair them or even increase their length. Many of these studies take aim at telomerase, the enzyme that replenishes telomeres as they degrade. It may stave off aging for a while, but in the end telomerase is like bailing water with a bucket – the ship is still going to sink.
To hopefully find a way to lend telomerase a hand, the Arizona State researchers looked closer at how exactly it works. The enzyme encodes a repeating string of six nucleotides – GGTTAG – onto the tips of chromosomes, but the team also noticed something new. After each sequence there's a pause signal while the cycle restarts, but that signal stays active during the next sequence, which could be reducing the efficiency of the enzyme.
"Telomerase has a built-in braking system to ensure precise synthesis of correct telomeric DNA repeats," says Julian Chen, lead researcher on the study. "This safe-guarding brake, however, also limits the overall activity of the telomerase enzyme. Finding a way to properly release the brakes on the telomerase enzyme has the potential to restore the lost telomere length of adult stem cells and to even reverse cellular aging itself."
The researchers say that targeting this pause signal could "supercharge" the function of telomerase, keeping adult stem cells healthier for longer. While that's an intriguing line of research to follow, the team cautions that there's a fine line to walk here. Like the brakes on a car, this signal seems to be an important safety feature – removing it entirely can lead to a crash.
In this case, a "crash" means cancer. Tumors are basically cells growing out of control, so it's not surprising that cancer cells have been known to hijack telomerase to keep themselves growing. To avoid that pitfall, the researchers say that any potential anti-aging treatment that eases the brakes on telomerase would need to only target adult stem cells.
The research was published in The EMBO Journal.
Source: Arizona State University
