Research Papers: Gerotarget (Focus on Aging):
A mutation in the NADH-dehydrogenase subunit 2 suppresses fibroblast aging
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Marianne Schauer1, Tina Kottek1, Madeleine Schönherr1, Animesh Bhattacharya1, Saleh M Ibrahim2, Misa Hirose2, Rüdiger Köhling3, Georg Fuellen4, Ulf Schmitz5, Manfred Kunz1
1Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig 04103, Germany
2Department of Dermatology, Allergology and Venereology, University of Lübeck, Lübeck 23538, Germany
3Department of Physiology, University of Rostock, Rostock 18057, Germany
4Department of Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock 18057, Germany
5Department of Systems Biology and Bioinformatics, University of Rostock, Rostock 18057, Germany
Marianne Schauer, e-mail: [email protected]
Keywords: aging, senescence, mitochondria, skin fibroblasts, p38MAPK signalling
Received: January 23, 2015 Accepted: February 08, 2015 Published: March 24, 2015
Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are implicated in premature aging syndromes. Here we investigated a single nucleotide exchange (leucine to methionine) at position nt4738 in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain. Primary fibroblasts derived from the conplastic mouse strain C57BL/6J-mtALR/LTJ with mutant enzyme, possessed high enzyme activity and ATP production and low ROS production. Furthermore, Nd2-mutant fibroblasts expressed lower senescence markers. Transcriptome analysis revealed that the members of the p38MAPK pathway were significantly downregulated in Nd2-mutant mice. In agreement, inhibition of p38MAPK with SB203580 enhanced proliferation and reduced cytokine secretion in fibroblasts. In Nd2-mutant mouse skin, the amount of Ki67-positive cells was significantly higher than in control skin. The higher amount of Ki67-positive cells and the thicker epidermis in Nd2-mutant mice strongly supported the in vitro data. In conclusion, Nd2 is a mitochondrial gene, involved in age-related signaling pathways.
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