Changes in Skin Structure and Integrity as a Function of Environment and Aging

Over the course of an individual’s life, human skin undergoes a steady process of morpho­logical, structural, and biochemical alterations that are characterized as fine lines/wrinkles, texture, uneven skin tone, hyperpigmented spots, and loss of elasticity and resilience [16]. There are several working theories on the key causative scenarios to help explain changes observed in the aging process in general [17], ranging from oxidative stress and mitochon­drial efficiency [18], telomere shortening [19], to hormonal changes [20]. One of the more germane theories for facial skin is the free radical theory of aging, which proposes that a lifetime of exposure to oxidative damage from intra – and extracellular radical oxygen spe­cies (ROS) will lead to an accumulation of damage that ultimately limits a cell’s ability to function at its proper capacitance in maintaining intracellular homeostasis and proper com­munication with the ECM. Compounding this is a reduction in the redox status and antioxi­dant defenses of cells, which limits the ability to neutralize ROS as they are continually generated from metabolic processes. ROS can be viewed as causing aberrant chemical, and thereby physical, changes to proteins and lipids, and also trigger specific molecular signal­ing pathways in response to the damage [21]. Relative to aging, diminished redox status in cells as well as mitochondrial efficiency and oxidative radical generation are generally key sources of ROS in human tissue. In skin, environmental challenges can dramatically increase transient or acute levels.

While several aging theories are applicable to changes in human skin, the two primary drivers of these changes that have been studied extensively include photodamage from chronic UV exposure and intrinsic (or chronological) aging [22]. While research over the past few decades has found that photoaging and intrinsic aging can be, to a certain extent, superimposed upon each other [23,24], it is quite clear that UV damage elicits the greatest changes that are observed in skin and can accelerate the processes that are already being impacted by chronological aging [25,26]. These changes include decreased ECM content by both stimulation of the degradation process and reduction in new synthesis as well as more direct chemical damage to the ECM. A combination of various cutaneous changes in the skin leads to the general observation of fine lines and wrinkles, which may be further exaggerated by muscular contractions and connections to the underlying hypodermis [27]. Other environmental insults do have an effect on the aging process of skin [28], but they are not as significantly impactful as chronic UV exposure.

The observation of gross morphological changes in skin as a function of photodamage have been extensively studied and noted. The actual pathogenic agents that drive these changes are UV-generated radical oxygen species and hydrogen peroxides, which can trig­ger a cascade of biophysical and biochemical processes, some of which are understood and others which are speculated (Fig. 2.3). More recently, the usage of molecular techniques has begun to shed light on the actual mechanistic changes that occur down to the gene expression level [29]. However, even at the molecular level, it remains difficult to separate the effects of chronological aging in addition to chronic UV exposure because the common denominators of ROS and oxidative stress have implications in both phenomena (albeit the radical formation is initiated from alternate sources).

Acute changes in the environment, particularly humidity and temperature, can quickly lead to changes in the overall appearance of the skin. In skin that undergoes acute photo­damage, the epidermis is often in a hyperplastic condition, which can be observed as a thickened epidermis. In the stratum corneum, the normal exfoliation of the corneocytes on the surface occurs via proteolytic cleavage of the desmosome connections, leading to sloughing of individual or small numbers of connected corneocytes. Disruption of this process when humidity conditions are altered can lead to an aberrant removal of the

uv

IRRADIATION

ANTlOXOANT

INCREASED

ROS

PRODUCTION

Figure 2.3 Schematic of oxidative stress via ROS as generated by intrinsic aging and UV exposure.

corneocytes and in some instances to a thickening of the epidermis. In addition, as a func­tion of age, alterations in the turnover rate as well as expression patterns of filaggrin can lead to further disruption of the stratum corneum and its barrier properties. Thus, elderly skin tends to appear more dry, rough, and less translucent than younger-aged skin [30]. In the event of a wound or UV damage to the skin, the overall repair process and heightened sensitivity to sunburn is delayed in older-aged skin as well.