Premature skin aging features rescued by inhibition of NADPH oxidase activity in XPC-deficient mice

J Invest Dermatol. 2015 Apr;135(4):1108-1118. doi: 10.1038/jid.2014.511. Epub 2014 Dec 1.


Xeroderma pigmentosum type C (XP-C) is characterized mostly by a predisposition to skin cancers and accelerated photoaging, but little is known about premature skin aging in this disease. By comparing young and old mice, we found that the level of progerin and p16(INK4a) expression, β-galactosidase activity, and reactive oxygen species, which increase with age, were higher in young Xpc(-/-) mice than in young Xpc(+/+) ones. The expression level of mitochondrial complexes and mitochondrial functions in the skin of young Xpc(-/-) was as low as in control aged Xpc(+/+)animals. Furthermore, the metabolic profile in young Xpc(-/-) mice resembled that found in aged Xpc(+/+) mice. Furthermore, premature skin aging features in young Xpc(-/-) mice were mostly rescued by inhibition of nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) activity by using a NOX1 peptide inhibitor, suggesting that the continuous oxidative stress due to overactivation of NOX1 has a causative role in the underlying pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA-Binding Proteins / genetics*
  • Humans
  • Keratinocytes / cytology
  • Lamin Type A
  • Light
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors*
  • NADH, NADPH Oxidoreductases / metabolism*
  • NADPH Oxidase 1
  • Nuclear Proteins / metabolism*
  • Oxidative Stress
  • Protein Precursors / metabolism*
  • Proteins / genetics
  • Reactive Oxygen Species / metabolism
  • Skin Aging*
  • Xeroderma Pigmentosum / metabolism
  • beta-Galactosidase / metabolism


  • Adaptor Proteins, Signal Transducing
  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA-Binding Proteins
  • Lamin Type A
  • Noxa1 protein, mouse
  • Noxo1 protein, mouse
  • Nuclear Proteins
  • Protein Precursors
  • Proteins
  • Reactive Oxygen Species
  • Xpc protein, mouse
  • prelamin A
  • NADH, NADPH Oxidoreductases
  • NADPH Oxidase 1
  • NOX1 protein, mouse
  • beta-Galactosidase

Supplementary concepts

  • Xeroderma Pigmentosum, Complementation Group C