title: Age-Dependent Decrease of Mitochondrial Complex II Activity in Human Skin Fibroblasts.
abstract: The mitochondrial theory of aging remains one of the most widely accepted aging theories and implicates mitochondrial electron transport chain dysfunction with subsequent increasing free radical generation. Recently, complex II of the electron transport chain appears to be more important than previously thought in this process, suggested predominantly by nonhuman studies. We investigated the relationship between complex II and aging using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0.015) but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0.008 and P = 0.001) and protein levels (P = 0.0006 and P = 0.005) of the succinate dehydrogenase complex subunit A and subunit B catalytic subunits of complex II, respectively. In addition, there was a significant decrease in complex II activity with age (P = 0.029) that was specific to senescent skin cells. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II.
authors.affiliation: Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Bowman
authors.affiliation: Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. Electronic address: mark.birch-machin@newcastle.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birch-Machin
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D042963:Electron Transport Complex II / Q000172:deficiency*; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D008661:Metabolism, Inborn Errors; D008928:Mitochondria / Q000235:genetics*; D028361:Mitochondrial Diseases; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015595:Skin Aging / Q000235:genetics* / Q000473:pathology; D013053:Spectrophotometry
chemical_list: D015415:Biomarkers; D042963:Electron Transport Complex II