Lookup NU author(s): Professor Mark Birch-Machin,
Dr Amy Bowman
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley-Blackwell Publishing Ltd., 2016.
For re-use rights please refer to the publisher's terms and conditions.
Oxidative stress is the resultant damage due to redox imbalances (increase in destructive free radicals [reactive oxygen species (ROS)] and reduction in antioxidant protection/pathways) and is linked to ageing in many tissues including skin. In ageing skin there are bioenergetic differences between keratinocytes and fibroblasts which provide a potential ageing biomarker. The differences in skin bioenergy are part of the mitochondrial theory of ageing which remains one of the most widely accepted ageing theories describing subsequent increasing free radical generation. Mitochondria are the major source of cellular oxidative stress and form part of the vicious cycle theory of ageing. External and internal sources of oxidative stress include UVR/IR, pollution (environment), lifestyle (exercise and diet), alcohol and smoking all of which may potentially impact on skin although many exogenous actives and endogenous antioxidant defence systems have been described to help abrogate the increased stress. This also links to differences in skin cell types in terms of the UVR action spectrum for nuclear and mitochondrial DNA damage (the latter a previously described UVR biomarker in skin). Recent work associates bioenergy production and oxidative stress with pigment production thereby providing another additional potential avenue for targeted anti-ageing intervention in skin. This new data supporting the detrimental effects of the numerous wavelengths of UVR may aid in the development of cosmetic/sunscreen design to reduce the effects of photoageing. Recently, complex II of the mitochondrial electron transport chain appears to be more important than previously thought in the generation of free radicals (suggested predominantly by non-human studies). We investigated the relationship between complex II and ageing 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 SDHA and SDHB 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, our study being the first to investigate these differences with senescence and skin age. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II. Our study provides a future potential biomarker for monitoring the progression of skin ageing.
Author(s): Birch-Machin MA, Bowman A
Publication type: Article
Publication status: Published
Journal: British Journal of Dermatology
Issue: Suppl. 2
Print publication date: 01/10/2016
Online publication date: 26/09/2016
Acceptance date: 25/07/2016
Date deposited: 17/10/2016
ISSN (print): 0007-0963
ISSN (electronic): 1365-2133
Publisher: Wiley-Blackwell Publishing Ltd.
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