Ribosomes stutter in their old age.

Nyström/EMBO

Anew study implicates a novel culprit in the accumulation of oxidative damage in aging cells. Increased protein oxidation may stem not from increased activity of free radicals or decreased levels of antioxidants, but from the higher error rate of ribosomes, according to a team led by Thomas Nyström of Göteborg University in Sweden.

The study delivers a blow to the popular rate-of-living hypothesis—the idea that lifespan and metabolic rate are negatively correlated. When the authors examined Escherichia coli cells that were in a starvation-induced state of senescence, they found no relationship between metabolic rate and protein oxidation. Instead, the numbers of misfolded or malformed proteins surged in the senescent cells, suggesting that ribosome fidelity might influence the rate of protein oxidation. Mutants with sloppy ribosomes had higher levels of oxidized proteins, whereas mutants with super-accurate ribosomes showed much lower levels of these proteins.

How would more errors during translation increase oxidative damage? Nyström and colleagues hypothesize that error-prone ribosomes make more malformed proteins that may be particularly susceptible to oxidative damage. They also suggest that a decline in ribosome fidelity, perhaps triggered by a shortage of charged tRNAs in older cells, might spur age-related oxidation in eukaryotic cells. ▪

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