Fewer Protein Synthesis Errors Linked to Longevity

Reducing naturally occurring errors in protein synthesis improves both health and lifespan, finds a new study in simple model organisms led by researchers at UCL and MRC London Institute of Medical Sciences. The findings, published in Cell Metabolism, are the first to demonstrate a direct link between fewer protein mistakes and longevity.

Lead author Ivana Bjedov said, “We commonly hear about DNA mutations, which can cause cancer, and are considered one of the underlying causes of aging. However, mistakes in proteins that affect organismal health are largely neglected, despite the fact that errors introduced during the synthesis of new proteins are much more frequent than mutations made during DNA replication.” For the current study, the team focused on protein errors and questioned if fewer mistakes would equate to improved health.

The scientists investigated an evolutionary ‘hyper-accuracy’ mutation, known as RPS23 K60R, found in the ribosomes of hyperthermophilic Archaea. Using genome editing, scientists engineered a metazoan ribosome to carry the identical mutation as the hyperthermophilic Archaea, and thereby replicated its effect on protein synthesis in simple model organisms, namely yeast, worms, and fruit flies.

The team observed that the organisms’ proteins had fewer errors and, as a result, the organisms became heat resistant and lived longer. “We have shown, for the first time, that changing a single amino acid in the ribosome decoding center reduces protein synthesis mistakes and improves an organism’s stress resilience and longevity,” first author Victoria Eugenia Martinez-Miguel concluded.