Mysterious Circular RNA May Extend Lifespan in Fruit Flies

Both insulin and insulin-like growth factor 1 (IGF-1) appear to play a major role in the ageing process. These two hormones activate a shared pathway that tells cells to grow and divide. When this signalling is reduced, for example in fruit flies genetically engineered to produce less insulin, lifespan is greatly extended. Why exactly this happens is not known, but recent research suggests that a mysterious molecule – circular RNA – may hold part of the answer.

Ribonucleic acid, or RNA, is part of our genetic code and present in every cell of our body. The best known form of RNA is a single linear strand, of which the function is well known and characterized. But there is also another type of RNA, so-called “circular RNA,” or circRNA, which forms a continuous loop that makes it more stable and less vulnerable to degradation. CircRNAs accumulate in the brain with age. Still, the biological functions of most circRNAs are not known and are a riddle for the scientific community. Now scientists from the Max Planck Institute for Biology of Aging have come one step closer to answer the question what these mysterious circRNAs do: one of them contributes to the aging process in fruit flies.

The researchers found a specific type of circular RNA, called circSfl, that was expressed at much higher levels in longer-lived fruit flies. In cells, normal linear RNA molecules serve as templates to produce proteins, but most circular RNAs do not produce proteins. However, circSfl did produce a protein: an enzyme similar to that produced by linear Sfl RNA, though exactly what role it might play in ageing is unknown.

“We want to understand how aging works and why the flies lacking insulin are long-lived. It seems like one of the mechanisms is circSfl. We now want to further investigate the aging process by looking at other circular RNAs also in other animals.” Because circular RNAs also accumulate in the mammalian brain, these findings most likely also have important implications for humans.

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