Caloric restriction and lifespan: a role for protein turnover?

Oxidative damage to cellular macromolecules has been postulated to be a major contributor to the ageing of diverse organisms. Oxidative damage can be limited by maintaining high anti-oxidant defenses and by clearing/repairing damage efficiently. Protein turnover is one of the main routes by which functional proteins are maintained and damaged proteins are removed. Protein turnover rates decline with age, which might contribute to the accumulation of damaged proteins in ageing cells. Interestingly, protein turnover rates are maintained at high levels in caloric restricted animals. Whether changes in protein turnover are a cause or a consequence of ageing is not clear, and this question has not been a focal point of modern ageing research. Here we survey work on protein turnover and ageing and suggest that powerful genetic models such as the nematode Caenorhabditis elegans are well suited for a thorough investigation of this long-standing question.