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Shortening of telomere length by metabolic factors in diabetes: protective effects of fenofibrate.

ABSTRACT: People with diabetes mellitus have shorter telomeres compared with non-diabetic subjects. The aim of this study was to investigate an in-vitro model of telomere shortening under diabetes metabolic conditions. The mechanisms of the accelerated telomere length attrition and the potential telomere protective action of fenofibrate with related cellular mechanisms were also examined. Human dermal fibroblasts were passaged and cultured in normal (5.5 mM) or high (25 mM) D-glucose, across 7 days with hydrogen peroxide (H₂O₂), glucosamine (GA), or glycated albumin (AGEs-BSA). Relative telomere length (RTL) was determined by qPCR. The expression of shelterin complex members which regulate telomere stability were measured by qRT-PCR and Western immunoblot. Culture in high glucose decreased RTL compared with normal glucose: H₂O₂ and GA lowered the RTL after 7 days (each P?2O₂ and to a lesser extent by GA. Trf1 and Trf2 protein were induced by H₂O_2. Co-treatment with fenofibrate (100 ?M) significantly attenuated the reduction in RTL caused by H₂O₂ and GA and prevented Trf induction by H₂O₂. However knockdown of Trf1 and Trf2 expression using specific siRNA did not prevent H₂O₂ effects to lower RTL, thus implicating factors other than these Trfs alone in the fenofibrate protection against the H₂O₂ induction of RTL lowering. These in vitro findings demonstrate that diabetic conditions can induce telomere shortening and that fenofibrate has protective effects on telomere attrition, through as yet undefined mechanisms.

SUBMITTER: Sutanto SSI

PROVIDER: S-EPMC6946782 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Shortening of telomere length by metabolic factors in diabetes: protective effects of fenofibrate.

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