The purpose of this article is to discuss some of the key target molecules and receptors involved with aging mechanisms. As scientists learn more about the complex biochemical processes involved with aging, an increasing number of these loci are discovered and may be selected as targets for cosmeceutical ingredients. As the number of potential known targets continues to grow, the problem will be narrowing the field to a few well-chosen sites of action from the plethora of possibilities.
It is impossible to discuss all major aging receptors and target molecules here, thus an effort was made to highlight only those of recent interest; some have no doubt been omitted. Ten to 15 years ago, scientific knowledge was expected to converge on a few mechanisms, or possibly even a single gene that controlled aging.1 However, although a case could be made for “aging genes” in nematode worms,2 knowledge of human aging processes seems to be diverging into more complex, intertwined processes with numerous negative and positive feedback loops. For the past 50 years, the Free Radical Theory of Aging primarily credited to D. Harman, MD, has been discussed and other aging theories often seemed to be subsets of this theory. More recently, however, it has become clear that there are many interrelated aging processes. Free radical damage as a cause of aging is now often referred to as the Oxidative Stress/Inflammation mechanism of aging, and inflammatory processes are being recognized as key in the biochemical and physiologic decline observed in the aged individual—as are the processes of glycation, protein messaging and epigenetics, DNA damage and others. These mechanisms are reviewed here. Note that this article will not suggest specific active ingredients for these sites but rather describe the targets themselves.
Glycation and Glycosylation
Glycation occurs when a sugar moiety becomes attached to a protein. Collagen is the most common protein found in the body and most of it is harbored in the skin, although joints and blood vessels also contain large amounts of collagen. Following the attachment of glucose to collagen, deformability and resilience decrease and the molecule becomes stiff. Individuals subject to increased glycation include diabetics, particularly if “brittle” or under poor control; the obese; and the aged. In those over 40, age is more important than amount of obesity (BMI) in contributing to increased rates of glycation and insulin resistance.