Monday, 30 May 2011
Summary of article: “Photoaging: Mechanism and repair”
Brief Introduction
The deterioration of biological functions and ability to manage metabolic stress is one of the major consequence of the aging process (1). Aging is a complex, progressive process which also leads to functional and esthetic changes in the skin (1). This process could result from both intrinsic, such that it is genetically determined, as well as extrinsic processes which include environmental factors (1).
Definition of Photoaging
Photoaging is the resulting effect of continuous, long-term ultraviolet (UV) exposure and sun damage on an intrinsically aged skin (1). Most often, fairer individuals are most severely affected. For photoaged skin, there would be a significant reduction in many functions of the skin (1).
Signs, symptoms and histopathology
The clinical signs and symptoms for a photoaged skin include dyspigmentation, laxity, a yellow hue, wrinkles, telangiectasia, leathery appearance, and cutaneous malignancies (1).
Additionally, photoaging could also result in an orderly maturation of keratinocytes and an increased in the cell population of the dermis where abundant, hyperplastic, elongated and collapsed fibroblasts and inflammatory infiltrates are found (1).
Photodamage could also characterised as the disorganisation of collagen fibrils which constitute most of the connective tissue and the accumulation of abnormal, amorphous, elastin-containing material (1). Fine wrinkles is another one of the prominent feature of a photoaged skin (1).
Effects of UV light on keratinocytes
UV and Molecular and Genetic Changes
UV radiation of appopximately 245 – 290 nm is maximally absorbed by DNA, where UVB is considered as a primary mutagen (1). UVB results in DNA mutations that arise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases (1). These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage (1).
UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS) which includes superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins (1).
UV and Pigmentation
UV exposure could also lead to inflammation and vasodilation which is clinically manisfested as sunburn (1). UV radiation activates the transcription factor, NF-κB, which is the first step in inflammation. NF-κB activation will result in the increase of proinflammatory cytokines eg interleukin 1 (IL-1), IL-6 vascular endothelial growth factor and tumor necrosis factor, TNF-α (1). This would then attract neutrophils which leads to an increase in oxidative damage through the generation of free radicals (1).
Additionally, UV radiation would cause the downregulation of an angiogenesis inhibitor, thrombospondin-1, and the upregulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor, in keratinocytes (1). These enhance angiogenesis and aid in the growth of UV-induced neoplasms (1).
UV and Immunosupression
It has also been reported that UV radiation would lead to local and systemic immunosuppression, due to DNA damage and altered cytokine expression (1). This has implications in cutaneous tumor surveillance (1).
UV and Extracellular Matrix
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 signalling kinases throughout the skin (1). The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), is expressed and activated (1). MMP-1 is a major metalloproteinases for collagen degradation. NF-κB, which is also activated by UV light, also increases the expression of MMP-9 (1).Exposure to UV radiation which is inadequate to cause sunburn can thus facilitate the degradation of skin collagen and lead to presumably, eventual photoaging (1).
UV and Retinoic acids and Photodamage
Retinoic acid (RA) is essential for normal epithelial growth and differentiation as well as for maintenance of normal skin homeostasis (1). UV radiation decreases the expression of both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in human skin which results in a complete loss of the induction of RA-responsive genes (1). It also would lead to an increase in activity of AP-1 pathway, increasing MMP activity and thus also resulting in a functional deficiency of vitamin A in the skin (1).
Endogenous Defense Mechanism Against UV radiation
Epidermal thickness
UV exposure which would lead to an increase in epidermal thickness could help protect from further UV damage (1).
Pigment
It has been reported in many cases that fairer individuals (lesser melanins) show more dermal DNA photodamage, infiltrating neutrophils, keratinocyte activation and IL-10 expression, increased MMPs after UV exposure (1). Therefore, the distribution of melanin provides protection from sunburn, photoaging and carcinogenesis by absorbing and scattering UV rays (1).
Repair of DNA mutation and apoptosis
When DNA is damaged by UV rays exposure, p53 transcription isactivated and cell will be arrested in the G1 phase so as to allow DNA repair by endogenous mechanisms like the nucleotide excision repair system (1). If the damage is too severe and cannot be repaired, it might trigger apoptosis to occur (1).
Tissue inhibitors of MMPs (TIMPs)
TIMPs regulate the activity of MMP. UV rays has been shown in many studies that it would induce TIMP-1 (1).
Antioxidants
The skin consists of several antioxidants which include vitamin E, coenzyme Q10, ascorbate, carotenoids, superoxide dismutase, catalase and glutathione peroxidase (1). These antioxidants provide protection from ROS produced (1). However, too much exposure to UV rays could lead to a significant reduction in the antioxidant supply, leading to oxidative stress (1). Hence, these antioxidants are essential in the skin's defense mechanism against UV radiation and photocarcinogenesis (1).
Treatment of Photoaging
Treatment and intervention for photoaging can be classified into a unique paradigm based on disease prevention (1).
Primary prevention is to reduce the risk factors before a disease or condition occurs that includes photoprotection or sun protection (1).
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 (1). This include the usage of retinoids, antioxidants, estrogens and growth factors or cytokines (1).
Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ameliorate its effects or delay its progress (1). Such tertiary prevention includes the use of chemical peels, resurfacing techniques like microdermabrasion, the use of ablative and nonablative laser systems, radiofrequency technology, the use of exotoxin Botulinum toxins and soft tissue augmentation, also known as fillers (1).
- Nur Liyanah Bte Mohd Zaffre
Monday, 30 May 2011
Summary of article: “Photoaging: Mechanism and repair”
Brief Introduction
The deterioration of biological functions and ability to manage metabolic stress is one of the major consequence of the aging process (1). Aging is a complex, progressive process which also leads to functional and esthetic changes in the skin (1). This process could result from both intrinsic, such that it is genetically determined, as well as extrinsic processes which include environmental factors (1).
Definition of Photoaging
Photoaging is the resulting effect of continuous, long-term ultraviolet (UV) exposure and sun damage on an intrinsically aged skin (1). Most often, fairer individuals are most severely affected. For photoaged skin, there would be a significant reduction in many functions of the skin (1).
Signs, symptoms and histopathology
The clinical signs and symptoms for a photoaged skin include dyspigmentation, laxity, a yellow hue, wrinkles, telangiectasia, leathery appearance, and cutaneous malignancies (1).
Additionally, photoaging could also result in an orderly maturation of keratinocytes and an increased in the cell population of the dermis where abundant, hyperplastic, elongated and collapsed fibroblasts and inflammatory infiltrates are found (1).
Photodamage could also characterised as the disorganisation of collagen fibrils which constitute most of the connective tissue and the accumulation of abnormal, amorphous, elastin-containing material (1). Fine wrinkles is another one of the prominent feature of a photoaged skin (1).
Effects of UV light on keratinocytes
UV and Molecular and Genetic Changes
UV radiation of appopximately 245 – 290 nm is maximally absorbed by DNA, where UVB is considered as a primary mutagen (1). UVB results in DNA mutations that arise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases (1). These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage (1).
UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS) which includes superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins (1).
UV and Pigmentation
UV exposure could also lead to inflammation and vasodilation which is clinically manisfested as sunburn (1). UV radiation activates the transcription factor, NF-κB, which is the first step in inflammation. NF-κB activation will result in the increase of proinflammatory cytokines eg interleukin 1 (IL-1), IL-6 vascular endothelial growth factor and tumor necrosis factor, TNF-α (1). This would then attract neutrophils which leads to an increase in oxidative damage through the generation of free radicals (1).
Additionally, UV radiation would cause the downregulation of an angiogenesis inhibitor, thrombospondin-1, and the upregulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor, in keratinocytes (1). These enhance angiogenesis and aid in the growth of UV-induced neoplasms (1).
UV and Immunosupression
It has also been reported that UV radiation would lead to local and systemic immunosuppression, due to DNA damage and altered cytokine expression (1). This has implications in cutaneous tumor surveillance (1).
UV and Extracellular Matrix
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 signalling kinases throughout the skin (1). The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), is expressed and activated (1). MMP-1 is a major metalloproteinases for collagen degradation. NF-κB, which is also activated by UV light, also increases the expression of MMP-9 (1).Exposure to UV radiation which is inadequate to cause sunburn can thus facilitate the degradation of skin collagen and lead to presumably, eventual photoaging (1).
UV and Retinoic acids and Photodamage
Retinoic acid (RA) is essential for normal epithelial growth and differentiation as well as for maintenance of normal skin homeostasis (1). UV radiation decreases the expression of both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in human skin which results in a complete loss of the induction of RA-responsive genes (1). It also would lead to an increase in activity of AP-1 pathway, increasing MMP activity and thus also resulting in a functional deficiency of vitamin A in the skin (1).
Endogenous Defense Mechanism Against UV radiation
Epidermal thickness
UV exposure which would lead to an increase in epidermal thickness could help protect from further UV damage (1).
Pigment
It has been reported in many cases that fairer individuals (lesser melanins) show more dermal DNA photodamage, infiltrating neutrophils, keratinocyte activation and IL-10 expression, increased MMPs after UV exposure (1). Therefore, the distribution of melanin provides protection from sunburn, photoaging and carcinogenesis by absorbing and scattering UV rays (1).
Repair of DNA mutation and apoptosis
When DNA is damaged by UV rays exposure, p53 transcription isactivated and cell will be arrested in the G1 phase so as to allow DNA repair by endogenous mechanisms like the nucleotide excision repair system (1). If the damage is too severe and cannot be repaired, it might trigger apoptosis to occur (1).
Tissue inhibitors of MMPs (TIMPs)
TIMPs regulate the activity of MMP. UV rays has been shown in many studies that it would induce TIMP-1 (1).
Antioxidants
The skin consists of several antioxidants which include vitamin E, coenzyme Q10, ascorbate, carotenoids, superoxide dismutase, catalase and glutathione peroxidase (1). These antioxidants provide protection from ROS produced (1). However, too much exposure to UV rays could lead to a significant reduction in the antioxidant supply, leading to oxidative stress (1). Hence, these antioxidants are essential in the skin's defense mechanism against UV radiation and photocarcinogenesis (1).
Treatment of Photoaging
Treatment and intervention for photoaging can be classified into a unique paradigm based on disease prevention (1).
Primary prevention is to reduce the risk factors before a disease or condition occurs that includes photoprotection or sun protection (1).
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 (1). This include the usage of retinoids, antioxidants, estrogens and growth factors or cytokines (1).
Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ameliorate its effects or delay its progress (1). Such tertiary prevention includes the use of chemical peels, resurfacing techniques like microdermabrasion, the use of ablative and nonablative laser systems, radiofrequency technology, the use of exotoxin Botulinum toxins and soft tissue augmentation, also known as fillers (1).
- Nur Liyanah Bte Mohd Zaffre
