Inhibiting Cathepsin G to Protect Against Photoaging and Infra’aging

Photoaging refers to premature skin aging that results from chronic exposure to solar radiation or other sources that mimick solar effects. Until recently, photoaging essentially was linked to the ultraviolet (UV) portion of the solar spectrum; specifically, to UVB and UVA rays with wavelengths in the 290–400 nm range. UVB is absorbed by chromophores in the epidermis and is responsible for sunburn, whereas the less energetic UVA penetrates more deeply into the dermis and is associated with premature aging. Both UVB and UVA may also cause cancer and immunosuppression.1, 2

However, the solar spectrum is much broader, and attention is now turning toward infrared radiation (IR), i.e., the 760 nm–1 mm end of the rainbow. IR can be divided into IRA, IRB and IRC, and while all three have low energy and may seem inoffensive, IRA penetrates deeply into the skin, even reaching the hypodermis (see Figure 1).3, 4 Moreover, nearly half of solar rays fall into the IR range, of which 30% is IRA, versus around just 5% for UV.3 As a consequence, any effect of IRA on skin physiology deserves a closer look.

The hallmark of photoaged skin is an accumulation of elastolytic material in the upper and middle dermis, which occurs through a process known as solar elastosis.5 Together with collagen, elastic fibers normally form a support for cell attachment, since dermal fibroblasts need such anchoring to function properly. Chronic sun exposure activates various proteases that dismantle the extracellular matrix (ECM) scaffold, leaving amorphous material behind.

Cathepsin G has recently emerged as an important mediator of proteolytic ECM degradation in photoaging. This serine protease is secreted by inflammatory neutrophils and dermal fibroblasts. It is present in higher amounts in aged human skin than in younger skin, and its expression and/or activity can be further increased with UVA exposure.6, 7 Further, in one animal model of photoaging, a cathepsin G inhibitor prevented UVB-induced ECM degradation, suggesting activation of the enzyme by UVB as well.8

More in Actives