Telomerase deficiency promotes oxidative stress by reducing catalase activity

Telomere shortening and redox imbalance have been related to the aging Process. We used cultured mouse embryonic fibroblasts (MEF) isolated from mice lacking telomerase activity (Terc(-/-)) to analyze the redox balance and the functional consequences promoted by telomerase deficiency. Comparison with wild-type (WT) MEF showed that Terc(-/-) MEF had greater oxidant damage, showing higher superoxide anion and hydrogen peroxide production and lower catalase activity. Restoration of telomerase activity in Terc-/- MEF increased catalase expression and activity. TGF beta 1 and collagen type IV levels were higher in Terc(-/-) than in WT MEF. TGF-beta 1 promoter activity decreased when Terc(-/-) MEF were incubated with exogenous catalase, suggesting that catalase deficiency is the Cause of the TGF-beta 1 increase. Similar results were obtained in vivo. Homogenized renal cortex from 6-month-old Terc-/- showed higher oxidant capacity, lower catalase activity, greater oxidative damage, and higher TGF-beta 1 and fibronectin levels than that from WT mice. In Summary, telomerase deficiency reduces catalase activity, determining a redox imbalance that promotes overexpression of TGF-beta 1 and extracellular matrix proteins. (c) 2008 Elsevier Inc. All rights reserved.