Alpha-tocopherol modulates hydrogen peroxide-induced DNA damage and telomere shortening of human skin fibroblasts derived from differently aged individuals

Planta Med. 2010 Jun;76(9):869-75. doi: 10.1055/s-0029-1240812. Epub 2010 Jan 28.

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 H(2)O(2)-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, H(2)O(2)-induced oxidative stress, alpha-tocopherol treatment, and pre- and post-treatment with alpha-tocopherol for H(2)O(2)-induced oxidative stress. Our results showed that H(2)O(2)-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 H(2)O(2)-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 H(2)O(2)-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 H(2)O(2)-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 H(2)O(2)-induced telomere shortening by restoring the telomerase activity. It also modulated H(2)O(2)-induced DNA damage and this modulation was affected by donor age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Cellular Senescence / drug effects*
  • Cellular Senescence / genetics
  • DNA Damage / drug effects*
  • Drug Administration Schedule
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Hydrogen Peroxide
  • Oxidative Stress / drug effects*
  • Skin / drug effects*
  • Skin / metabolism
  • Telomerase / metabolism
  • Telomere / drug effects*
  • Telomere / ultrastructure
  • alpha-Tocopherol / pharmacology*

Substances

  • Hydrogen Peroxide
  • Telomerase
  • alpha-Tocopherol