Ageing is multifactorial and a natural, complex process. Many causes have been proposed, and in skin biology these are often divided into 'extrinsic' and 'intrinsic' causes of ageing. Extrinsic causes include lifestyle factors, such as how we live our daily lives, for example whether we live in cities that may be highly polluted or live in a more rural setting but with perhaps a lot of sun exposure. Certainly, sun damage is a leading cause of ageing, even from indoor exposure through windows or from suberythemal levels of ultraviolet radiation . Smoking is another contributing factor in the production of fine lines and wrinkles, especially around the mouth area  and particularly for Asians. Stress, marital status and depression are other factors considered to be environmental or extrinsic causes of ageing .
Intrinsic causes of ageing are much less well understood, but nevertheless are the subject of a great deal of research and investigation. These include genetic factors, such as a familial predisposition to cancer, as well as how and when hormonal changes affect the body. This could be described as being analogous to the internal ageing clock ticking away. The cosmetic industry has a significant focus on preserving the youthful appearance of skin. Many products are designed to affect the appearance of ageing, as youthful skin is often perceived to be more healthy and attractive than aged skin. These products may prevent damage from occurring by offering sun protection (SPF-containing products) or by offering to improve the appearance of already existing signs of ageing, for example fine lines and wrinkles.
In this work, a potential new source of intrinsic ageing is described and data showing its correlation with an aged appearance is presented.
arNOX (age-related NADH oxidase) enzyme is one in a class of newly identified ECTO-NOX (external NADH oxidase or ENOX) proteins that have been shown to be located on external cell membranes . ECTO-NOX proteins are a family of functionally related proteins capable of oxidising reduced quinines  and are involved in plasma membrane oxidation-reduction reactions . In investigating this class of proteins, Morre et al.  discovered evidence that a member of the ECTO-NOX family increases in activity several fold as an individual ages. They called this protein age-related NOX (arNOX) . Unlike other ENOX proteins that carry out four electron transfers to molecular oxygen and form water, the arNOX protein is unique because it generates superoxide at the cell surface  (Figure 1). Free radical damage has been proposed as a major cause of skin ageing, and therefore, an enzyme in the body that produces free radicals and increases activity as we age, may play a role in the intrinsicmechanisms of skin ageing.
Initially, arNOX was isolated from the serum of older individuals (70-100 years), with lower levels being found in the serum of young individuals (20-40 years). The circulating form of arNOX increases markedly in human sera and in lymphocytes of individuals after age 50. An important question was whether this enzyme...