Age-related changes in oxidized proteins.

TLDR

Oxidative inactivation of key metabolic enzymes by mixed‑function oxidation systems has been previously described. The study examined oxidatively modified protein levels in two aging model systems, given that such enzymes accumulate as inactive forms during cellular aging. Treatment of glucose‑6‑phosphate dehydrogenase with a mixed‑function oxidation system produced oxidative modification and increased heat lability. Oxidatively modified proteins rise with age in erythrocytes, correlating with loss of marker enzyme activity; in normal fibroblasts they increase only after age 60, whereas fibroblasts from progeria or Werner's syndrome show markedly higher levels; these observations suggest that aging‑related loss of enzyme function and heat lability may stem partly from oxidative modification by mixed‑function oxidation systems.

Abstract

We have previously described the oxidative inactivation of several key metabolic enzymes by a variety of mixed function oxidation systems. Because many of the enzymes which are inactivated have been shown by others to accumulate as inactive or less active forms during cellular aging, we have examined the levels of oxidatively modified proteins in two model systems used for studies on aging. The results show that levels of oxidatively modified proteins increase with age in circulating erythrocytes, and this change is correlated with the loss of marker enzyme activity. Our studies also show that in cultured fibroblasts from normal donors the levels of oxidatively modified proteins increase only after the age of 60. However, the levels of oxidatively modified proteins in fibroblasts from individuals with progeria or Werner's syndrome are significantly higher than age-matched controls. Moreover, treatment of glucose-6-phosphate dehydrogenase with a mixed function oxidation system leads to oxidative modification and increased heat lability of the enzyme. Taken together these results suggest that loss of functional enzyme activity and increased heat lability of enzymes during aging may be due in part to oxidative modification by mixed function oxidation systems.