In the present work, we indicate that copper is involved in the senescence of human diploid fibroblasts and we describe mechanisms to explain it. Using different techniques, we show for the first time an accumulation of copper in cells during replicative senescence. This accumulation seems to be colocalized with lipofuscin. Second, we observed that an incubation of cells with copper sulfate induced oxidative stress, antioxidant response and premature senescence. Antioxidant molecules reduced the appearance of premature senescence. Third, we found that Nrf2 transcription factor was activated and regulated the expression of genes involved in antioxidant response while p38 MAPK regulated the appearance of premature senescence.

Emmanuelle Boilan

Virginie Winant

Elise Dumortier

Jean-Pascal Piret

François Bonfitto

Heinz D. Osiewacz

Florence Debacq-Chainiaux

Olivier Toussaint

Role of p38MAPK and oxidative stress in copper-induced senescence

铜诱导衰老中p38MAPK和氧化应激的作用

Role of p38MAPK and oxidative stress in copper-induced senescence

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