Photoaging

Photoaging or photoageing[1] (also known as "dermatoheliosis"[2]) is a term used for the characteristic changes to skin induced by chronic UVA and UVB exposure.[3]:29 Tretinoin is the best studied retinoid in the treatment of photoaging[4]

The deterioration of biological functions and ability to manage metabolic stress is one of the major consequences of the aging process. Aging is a complex, progressive process that leads to functional and esthetic changes in the skin. This process can result from both intrinsic (i.e., genetically determined) as well as extrinsic processes (i.e., environmental factors). Photoaging is attributed to continuous, long-term exposure to ultraviolet (UV) radiation of approximately 300–400 nm, either natural or synthetic, on an intrinsically aged skin.

Effects of UV light

Molecular and genetic changes

UVB rays are a primary mutagen that can only penetrate through the epidermal (outermost) layer of the skin, resulting in DNA mutations. These mutations arise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases. These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage.[5][6]

The epidermal layer does not contain any blood vessels or nerve endings but melanocytes and basal cells are embedded in this layer. Upon exposure to UVB rays, melanocytes will produce melanin, a pigment that gives the skin its color tone. However, UVB will cause the formation of freckles and dark spots, both of which are symptoms of photoaging. With constant exposure to UVB rays, signs of photoaging might appear and precancerous lesions or skin cancer may develop.

UVA rays are able to penetrate deeper into the skin as compared to UVB rays. Hence, in addition to the epidermal layer, the dermal layer will also be damaged. The dermis is the second major layer of the skin and it comprises collagen, elastin, and extrafibrillar matrix which provides structural support to the skin. However, with constant UVA exposure, the size of the dermis layer will be reduced, thereby causing the epidermis to start drooping off the body. Due to the presence of blood vessels in the dermis, UVA rays can lead to dilated or broken blood vessels which are most commonly visible on the nose and cheeks. UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS), which include superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins.

Pigmentation

UV exposure can also lead to inflammation and vasodilation which is clinically manifested as sunburn. UV radiation activates the transcription factor, NF-κB, which is the first step in inflammation. NF-κB activation results in the increase of proinflammatory cytokines, for example: interleukin 1 (IL-1), IL-6 vascular endothelial growth factor, and tumor necrosis factor (TNF-α). This then attract neutrophils which lead to an increase in oxidative damage through the generation of free radicals.

Additionally, UV radiation would cause the down-regulation of an angiogenesis inhibitor, thrombospondin-1, and the up-regulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor, in keratinocytes. These enhance angiogenesis and aid in the growth of UV-induced neoplasms.

Immunosuppression

It has been reported that UV radiation leads to local and systemic immunosuppression, due to DNA damage and altered cytokine expression. This has implications in cutaneous tumor surveillance. The Langerhans cells may undergo changes in quantity, morphology, and function due to UV exposure and may eventually become depleted. One proposed explanation for this immunosuppression is that the body is attempting to suppress an autoimmune response to inflammatory products resulting from UV damage.

Degradation of collagen

UV exposure would also lead to the activation of receptors for epidermal growth factor, IL-1, and TNF-α in keratinocytes and fibroblasts, which then activates signaling kinases throughout the skin via an unknown mechanism.[7] The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), is expressed and activated. MMP-1 is a major metalloproteinases for collagen degradation. This entire process is aided by the presence of reactive oxygen species that inhibits protein-tyrosine phosphatases via oxidation, thereby resulting in the up-regulation of the above-mentioned receptors. Another transcription factor NF-κB, which is also activated by UV light, also increases the expression of MMP-9.

The up-regulation of MMP can occur even after minimal exposure to UV, hence, exposure to UV radiation which is inadequate to cause sunburn can thus facilitate the degradation of skin collagen and lead to presumably, eventual photoaging. Thus, collagen production is reduced in photoaged skin due to the process of constant degradation of collagen mediated by MMPs.

In addition, the presence of damaged collagen would also down-regulate the synthesis of new collagen. The impaired spreading and attachment of fibroblasts onto degraded collagen could be one of the contributing factors to the inhibition of collagen synthesis.

Retinoic acids and photodamage

Retinoic acid (RA) is essential for normal epithelial growth and differentiation as well as for maintenance of normal skin homeostasis. UV radiation decreases the expression of both retinoic acid receptors and retinoid X receptors in human skin, thereby resulting in a complete loss of the induction of RA-responsive genes. It also leads to an increase in activity of the AP-1 pathway, increasing MMP activity and thus resulting in a functional deficiency of vitamin A in the skin.

Signs, symptoms and histopathology

Early symptoms of photoaging:

Symptoms of photoaging attributed to prolonged exposure to UV:

In addition to the above symptoms, photoaging can also result in an orderly maturation of keratinocytes and an increase in the cell population of the dermis where abundant; hyperplastic, elongated and collapsed fibroblasts and inflammatory infiltrates are found.

Photodamage can also be characterized as a disorganization of the collagen fibrils that constitute most of the connective tissue, and the accumulation of abnormal, amorphous, elastin-containing material, a condition known as actinic elastosis.

Defense Mechanisms

Endogenous defense mechanisms provide protection of the skin from damages induced by UV.

Epidermal thickness

UV exposure which would lead to an increase in epidermal thickness could help protect from further UV damage.

Pigment

It has been reported in many cases that fairer individuals who have lesser melanin pigment show more dermal DNA photodamage, infiltrating neutrophils, keratinocyte activation, IL-10 expression and increased MMPs after UV exposure. Therefore, the distribution of melanin provides protection from sunburn, photoaging, and carcinogenesis by absorbing and scattering UV rays.

Repair of DNA mutation and apoptosis

The damage of DNA due to exposure of UV rays will lead to expression of p53, thereby leading to eventual arrest of the cell cycle. This allows DNA repair mediated by endogenous mechanisms like the nucleotide excision repair system. In addition, apoptosis occurs if the damage is too severe. However, the apoptotic mechanisms decline with age, and if neither DNA repair mechanism nor apoptosis occurs, cutaneous tumorigenesis may result.

Tissue inhibitors of MMPs (TIMPs)

TIMPs regulate the activity of MMP. Many studies have shown that UV rays would induce TIMP-1.

Antioxidants

The skin contains several antioxidants, including vitamin E, coenzyme Q10, ascorbate, carotenoids, superoxide dismutase, catalase, and glutathione peroxidase. These antioxidants provide protection from reactive oxygen species produced during normal cellular metabolism. However, overexposure to UV rays can lead to a significant reduction in the antioxidant supply, thus increasing oxidative stress. Hence, these antioxidants are essential in the skin's defense mechanism against UV radiation and photocarcinogenesis.

Treatment

Treatment and intervention for photoaging can be classified into a unique paradigm based on disease prevention.

Primary prevention

Primary prevention aims to reduce the risk factors before a disease or condition occurs. Primary prevention for photoaging involves mainly sun protection that comes in many forms like sun avoidance, sun protective clothing, and sunscreens.

UV exposure would be the strongest between 10am and 4pm in spring and summer, and sun avoidance is encouraged during these hours. If one cannot avoid exposure to the sun, then clothing, hats and sunglasses that protect from sun exposure should be fully utilized. Broad-spectrum sunscreens that have a sun protection factor (SPF) of at least 30 should be used when one gets frequent sun exposure.

Secondary protection

Secondary protection refers to early detection of disease, potentially while still asymptomatic, to allow positive interference to prevent, delay, or attenuate the symptomatic clinical condition. This includes the following:

Tertiary prevention

Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ameliorate its effects or delay its progress. Such tertiary prevention includes the use of chemical peels, resurfacing techniques (e.g. micro-dermabrasion), ablative or non-ablative laser resurfacing, radio-frequency technology, soft tissue augmentation (also known as fillers), and botulinum toxins. Photorejuvenation procedures are performed by dermatologists to reduce the visible symptoms.

See also

References

  1. ↑ Helfrich, Y. S.; Sachs, D. L.; Voorhees, J. J. (Jun 2008). "Overview of skin aging and photoaging" (PDF). Dermatology nursing / Dermatology Nurses' Association 20 (3): 177–183; quiz 183. ISSN 1060-3441. PMID 18649702.
  2. ↑ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
  3. ↑ James, William D.; Berger, Timothy G.; (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
  4. ↑ Stefanaki, C.; Stratigos, A.; Katsambas, A. (2005). "Topical retinoids in the treatment of photoaging". Journal of Cosmetic Dermatology 4 (2): 130–134. doi:10.1111/j.1473-2165.2005.40215.x. PMID 17166212.
  5. ↑ http://www.dermatology.ca/photoaging
  6. ↑ http://911skin.com/uvbubarays.html
  7. ↑ Spiekstra, SW; Breetveld; Rustemeyer; Scheper; Gibbs (September 2007). "Wound-healing factors secreted by epidermal keratinocytes and dermal fibroblasts in skin substitutes". Wound Repair and Regeneration 15 (5): 708–17. doi:10.1111/j.1524-475X.2007.00280.x. PMID 17971017. Retrieved October 7, 2014. The secretion of proinflammatory cytokines (IL-1alpha, TNF-alpha), chemokine/mitogen (CCL5) and angiogenic factor (vascular endothelial growth factor) by epidermal substitutes and tissue remodeling factors (tissue inhibitor of metalloproteinase-2, hepatocyte growth factor) by dermal substitutes was not influenced by keratinocyte-fibroblast interactions. The full-skin substitute has a greater potential to stimulate wound healing than epidermal or dermal substitutes. Both epidermal-derived IL-1alpha and TNF-alpha are required to trigger the release of dermal-derived inflammatory/angiogenic mediators from skin substitutes.

External links

This article is issued from Wikipedia - version of the Friday, September 04, 2015. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.