Alpha-tocopherol Modulates Hydrogen Peroxide-Induced DNA Damage and Telomere Shortening of Human Skin Fibroblasts Derived from Differently Aged Individuals

Abstract

Antioxidants such as vitamin E may act differently on skin cells depending on the age of the skin and the level of oxidative damage induced. The effects of alpha-tocopherol (ATF) on H₂O₂-induced DNA damage and telomere shortening of normal human skin fibroblast cells derived from young and old individual donors were determined. Fibroblasts were divided into five groups; untreated control, H₂O₂-induced oxidative stress, alpha-tocopherol treatment, and pre- and post-treatment with alpha-tocopherol for H₂O₂-induced oxidative stress. Our results showed that H₂O₂-induced oxidative stress increased DNA damage, shortened the telomere length and reduced the telomerase activity (p < 0.05) in fibroblasts obtained from young and old donors. Pre- and post-treatment with alpha-tocopherol protected against H₂O₂-induced DNA damage in fibroblasts obtained from young individuals (p = 0.005; p = 0.01, respectively). However, in fibroblasts obtained from old individuals, similar protective effects were only seen in cells pretreated with alpha-tocopherol (p = 0.05) but not in the post-treated cells. Protection against H₂O₂-induced telomere shortening was observed in fibroblasts obtained from both young and old donors which were pre-treated with alpha-tocopherol (p = 0.009; p = 0.008, respectively). However, similar protective effects against telomere shortening in fibroblasts obtained from both young and old donors were not observed in the post-treated fibroblasts. Protection against H₂O₂-induced telomerase activity loss was observed only in fibroblasts obtained from old donors which were pretreated with alpha-tocopherol (p = 0.04) but not in fibroblasts obtained from young donors. Similar protective effects against telomerase activity loss in fibroblasts obtained from both young and old donors were not observed in the post-treated fibroblasts. In conclusion, alpha-tocopherol protected against H₂O₂-induced telomere shortening by restoring the telomerase activity. It also modulated H₂O₂-induced DNA damage and this modulation was affected by donor age.

Key words

alpha‐tocopherol - DNA damage - telomeres - telomerase - oxidative stress - aging

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