Circular RNAs accumulate in aging cells, and that's no side effect
Aging is accompanied by a silent buildup of circular RNA molecules inside cells. Researchers long assumed this was a consequence of cellular decline. New research in worms suggests it may also be a cause.
Circular RNAs are a relatively recently discovered class of molecules. Unlike most RNA species, they have no beginning and no end: they form a closed loop that cells cannot easily break down. In young cells, they are cleared away quickly. In older cells, they accumulate, like debris on a floor that gets swept less and less often.
The question was: do they cause problems, or are they simply a marker of a cell that is already in decline? Researchers working with the roundworm Caenorhabditis elegans identified a protein called RNASEK that normally degrades circular RNAs. As the worm ages, RNASEK levels in the cell drop, giving circular RNAs the opportunity to build up. By artificially maintaining higher levels of RNASEK, the researchers were able to curb that accumulation, and the worms lived longer.
From correlation to causation
This is a methodological point that is crucial in aging research. Many hallmarks of aging are correlations: things that occur alongside cellular decline. But whether they are driving the aging process or merely along for the ride is an entirely different question. By intervening, through RNASEK overexpression, and observing what happens, the researchers make a causal argument. The lifespan extension in C. elegans was measurable.
That said, C. elegans is a nematode with exactly 959 body cells and a lifespan of just a few weeks. Its relevance to complex mammals, let alone humans, has yet to be demonstrated. The aging biology of a worm differs substantially from that of a person. Even so, the fact that the same mechanism, declining levels of an RNA-degrading protein, buildup of circular RNAs, accelerated deterioration, has also been observed in mammalian tissue is a reason to take it seriously.
A new point of intervention
If circular RNA accumulation genuinely contributes to aging in humans, it opens up a new class of potential interventions. Using RNASEK itself as a therapeutic target is technically challenging; manipulating protein levels in specific tissues is complex. But the finding at least identifies a mechanism that had previously gone unnoticed. How far this translates into a treatable target in human tissue is a question that follow-up research will need to answer in the years ahead.