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Guest Columnist Author: Zoe D. Draelos, M.D., Editor in Chief, Journal of Cosmetic Dermatology Last Updated: Sep 7, 2017 - 10:11:17 PM

Have You Ever Wondered Why Some People Look Younger Than Their Actual Age?

By Zoe D. Draelos, M.D., Editor in Chief, Journal of Cosmetic Dermatology
Apr 12, 2009 - 9:23:15 AM

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( - Are you destined to age at the same rate as your mother? After all, you’ve stayed out of the sun and haven’t picked up smoking – both major culprits for environment aging that cause those dreaded age spots and discoloration. And you’re long past making those funny faces given mom’s advice that your face may just stay that way, helping you to avoid those line and wrinkles that come from mechanical aging. But what about biological aging – the things that age you from the inside out?

Scientists have long believed that biological aging results from changes – perhaps linked to hormones or genes – within the body, and it is particularly noticeable in the appearance of your skin. However, until recently, little was known about the actual sources of aging and if they can be slowed.

arNOX Identified as a Source of Biological Aging

Over the last decade, researchers at Purdue University made considerable progress in elucidating NOX (NADH oxidase) proteins. For example, normal, or constitutive, NOX (cNOX) and tumor NOX (tNOX) were characterized and specific inhibitors for tNOX protein have been identified(1). During this work to further the understanding of NOX proteins, a third, very unique superoxide-generating NOX was observed. A key characteristic of this protein was that its activity increased with advanced age, and thus it was dubbed ‘age-related NOX’ or arNOX.

Classified as an ECTO-NOX protein, arNOX enzymes are external cell-surface located and are capable of being shed into circulation. arNOX has been found in cells and fluids tested, including the keratinocytes, fibroblasts, saliva, serum, perspiration and urine. Unlike other NOX proteins, which carry out four electron transfers to molecular oxygen to form water, arNOX creates the free radical superoxide. Superoxide leads to the formation of H2O2 and other reactive oxygen species capable of damaging circulating lipoproteins, adjacent cells and components of the skin’s extracellular matrix, such as collagen and elastin. It is speculated that over time the local production of free radicals in the skin could damage the components of the skin, eventually contributing to visible signs of aging in the skin.

arNOX Increases with Age

arNOX activity has been shown to increase with age starting between 35 and 45 years of age. Research presented at International Investigative Dermatology (May 2008, Kyoto, Japan) found that arNOX activity in tissue samples was positively correlated to age, independent of environmental exposure(2). arNOX activity levels were collected from saliva, serum, sun-protected and unprotected dermis, and sun-protected and unprotected epidermis (punch biopsies). Across all tissue samples, arNOX activity was positively correlated with age. Younger individuals (around 30 years) had little or no arNOX activity and the activity levels of this enzyme appear highest between the ages of 55 to 65.

The Appearance of Aging is Linked to arNOX

In another study that was presented at the 25th International Federation of the Societies of Cosmetic Chemists Congress (October 2008, Barcelona, Spain) a correlation was identified between arNOX activity levels and an individual’s appearance(3). Women with higher arNOX activity appeared to be an average of seven years older than their actual chronological age; whereas, women with lower arNOX activity appeared to be an average of seven years younger than their chronological age.

Preventing the Visible Signs of Aging

Medical research and technology is moving beyond effectively addressing disease symptoms to identifying root causes. This trend is being applied commercially in new anti-aging therapies, particularly for skin care. The demonstrated correlation between arNOX activity levels and age and appearance is an exciting breakthrough in understanding a source of biological aging. For the first time, rather than simply addressing the signs and symptoms of aging after they occur, a biological source of aging can be targeted. Limiting the production of superoxide from arNOX may prove to be a superior anti-aging therapy because it prevents the actual formation of free radicals at their source, thus mitigating their damage. Traditional therapies focus on neutralizing existing free radicals, as well as repairing damage that has already occurred. This new understanding of biological aging and its effect on skin appearance opens new doors for anti-aging skin research.


1. NOX Technologies, Inc. Ecto-NOX Proteins. Retrieved 17 February 2009 from

2. Kern, D., Draelos, Z.D., Morré, D.M., and Morré, D.J. Age-related NADH Oxidase (arNOX) Activity of Epidermal Punch Biopsies Correlate with Subject Age and arNOX Activities of Serum and Saliva. Supplement to the Journal of Investigative Dermatology, April 2008; 128(1), S57.

3. Rehmus, WE, Kern, DG, Janjua, R, Knaggs, HE, Morré, DM, Morré, DJ. (October 2008). A Randomized Pilot Study Of the Relationship Between arNOX Levels and Appearance of Skin Aging in Healthy Women. Poster session presented at the 25th International Federation of Societies of Cosmetic Congress, Barcelona Spain.

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