The major enzyme of the methionine sulfoxide reductase (Msr) system is MsrA. Senescing msrA knockout mother yeast cells accumulated significant amounts of protein-carbonyl both at 5 generation-old (young) and 21 generation-old (old) cultures, while the control mother cells showed significant levels of protein-carbonyl mainly in the old culture. The Msr activities of both yeast strains declined with age and exposure of cells to H(2)O(2) caused an accumulation of protein-carbonyl especially in the msrA knockout strain. It is suggested that a compromised MsrA activity may serve as a marker for non-replicative aging.