Sun Protection

Intrinsic and extrinsic factors in skin ageing: a review.

As the proportion of the ageing population in industrialized countries continues to increase, the dermatological concerns of the aged grow in medical importance. Intrinsic structural changes occur as a natural consequence of ageing and are genetically determined. The rate of ageing is significantly different among different populations, as well as among different anatomical sites even within a single individual. The intrinsic rate of skin ageing in any individual can also be dramatically influenced by personal and environmental factors, particularly the amount of exposure to ultraviolet light. Photodamage, which considerably accelerates the visible ageing of skin, also greatly increases the risk of cutaneous neoplasms. As the population ages, dermatological focus must shift from ameliorating the cosmetic consequences of skin ageing to decreasing the genuine morbidity associated with problems of the ageing skin. A better understanding of both the intrinsic and extrinsic influences on the ageing of the skin, as well as distinguishing the retractable aspects of cutaneous ageing (primarily hormonal and lifestyle influences) from the irretractable (primarily intrinsic ageing), is crucial to this endeavour.

Int J Cosmet Sci. 2008 Apr;30(2):87-95

The age of skin cancers.

Cancer affects two major cell types in the human skin: epithelial cells and melanocytes. Aging and a previous history of ultraviolet light exposure are major risk factors for skin cancers, including basal and squamous cell carcinomas and melanomas. However, melanomas, which are the most deadly of the skin tumors, display two intriguing characteristics: The incidence is increased and the prognosis is worse in males over 60 years as compared with females of the same age. This Perspective discusses possible reasons for age and gender as melanoma risk factors, as well as the need for studies aimed at unraveling the molecular mechanism of such puzzling events.

Sci Aging Knowledge Environ. 2006 May 24;2006(9):pe13

Skin cancer trends in Northern Ireland and consequences for provision of dermatology services.

BACKGROUND: The incidence of skin cancer, both melanoma and nonmelanoma skin cancer (NMSC), is rising throughout the world. The evaluation of trends in skin cancer will allow better planning of the future development of skin cancer services. OBJECTIVES: Using data collected from the Northern Ireland Cancer Registry (NICR), the incidence of the three major cutaneous cancers, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM), was determined and the workload associated with their management assessed. METHODS: The records of patients with a first diagnosis of BCC, SCC or MM occurring between 1993 and 2002 were retrieved from the NICR database. The annual age- and sex-adjusted incidence rates of all three skin cancers were computed per 100,000 person-years by direct standardization according to the European Standard Population. Trends in incidence were estimated by calculating the estimated annual percentage change using Microsoft Excel. For patients registered with the NICR as having BCC, SCC or MM, the number of pathological reports where malignant samples had been examined was counted and then summed to provide the number of specimens examined each year between 1993 and 2004. RESULTS: For all three cancers the age-specific rates for both males and females increased with age, except for MM in men aged 75 years and over, where the rates were seen to decrease. Over the 12-year period there was a 62% increase in the overall number of skin cancer samples processed by local pathology laboratories and a 20% increase in the number of patients. These data highlight the fact that many patients will have more than one skin cancer, which reinforces the benefit in collecting data for both patient and sample numbers in order to obtain a true reflection of the workload. The data have also shown that more affluent men and women have higher rates of BCC and MM than their less affluent counterparts. CONCLUSIONS: In view of the data presented it is clear that management of NMSC and MM will impose significant demands on services in the years ahead. This will impact on the entire multidisciplinary team. Future planning, in terms of manpower and resources, will prove essential if we are to remain in a position to manage our patients with these malignant tumours appropriately.

Br J Dermatol. 2007 Jun;156(6):1301-7

A Polypodium leucotomos extract inhibits solar-simulated radiation-induced TNF-alpha and iNOS expression, transcriptional activation and apoptosis.

In this report, we have examined the molecular basis of the photoprotective effect of a hydrophilic extract of the fern Polypodium leucotomos (PL) in vitro, using a solar simulator as the source of UV radiation (SSR). We found that pretreatment of human keratinocytes with PL inhibited SSR-mediated increase of tumor necrosis factor (TNF)-alpha and also abrogated nitric oxide (NO) production. Consistent with this, PL blocked the induction of inducible nitric oxide synthase (iNOS) elicited by SSR. In addition, PL inhibited the SSR-mediated transcriptional activation of NF-kappaB and AP1. Finally, we demonstrated that pretreatment with PL exerted a cytoprotective effect against SSR-induced damage, resulting in increased cell survival. Together, these data postulate a multifactor mechanism of protection not exclusively reliant on the antioxidant capability of PL, and strengthen the basic knowledge on the photoprotective effect of this botanical agent.

Exp Dermatol. 2007 Oct;16(10):823-9

Photoprotective properties of a hydrophilic extract of the fern Polypodium leucotomos on human skin cells.

The effect of a hydrophilic extract of the fern Polypodium leucotomos (PLE) has been investigated in terms of photoprotection against UV-induced cell damage. PLE efficiently preserved human fibroblast survival and restored their proliferative capability when the cells were exposed to UVA light. This effect was specific and dose-dependent. Photoprotection was not restricted to fibroblasts, as demonstrated by its effect on survival and proliferation of the human keratinocyte cell line HaCat. Finally, treatment of the cells with PLE prevented UV-induced morphological changes in human fibroblasts, namely disorganisation of F-actin-based cytoskeletal structures, coalescence of the tubulin cytoskeleton and mislocalization of adhesion molecules such as cadherins and integrins. Our in vitro results demonstrate the photoprotective effect of PLE on human cells and support its use in the preventive treatment of sunburning and skin pathologies associated with UV-mediated damage.

J Photochem Photobiol B. 2003 Apr;70(1):31-7

Photoprotective activity of oral polypodium leucotomos extract in 25 patients with idiopathic photodermatoses.

BACKGROUND: The incidences of idiopathic photodermatoses (IP) are increasing and the available therapeutic methods are often inadequate. AIM: To evaluate whether, in subjects affected by IP not responding to the usual available therapies, the oral administration of an extract of Polypodium leucotomos (PL) could provide an effective photoprotective activity. METHODS: 26 patients with polymorphic light eruption and two with solar urticaria were recruited to enter the study. The protocol excluded the use of ultraviolet protection filters or other drugs that could in some way interfere with exposure to light. All patients exposed themselves to sunlight while consuming 480 mg/day of PL orally. The response of the skin to sunlight exposure of 25 evaluable patients was compared with that occurring previously without administration of PL. RESULTS: With PL, we observed a relevant and statistically significant reduction of skin reaction and subjective symptoms. The tolerance of the drug has been excellent. CONCLUSION: PL extract administration has shown to be an effective and safe method, leading to a significant protection of skin in IP.

Photodermatol Photoimmunol Photomed. 2007 Feb;23(1):46-7

Polypodium leucotomos extract: a nutraceutical with photoprotective properties.

Ultraviolet (UV) irradiation causes multifaceted damage to the skin and adjacent tissue layers, and is one of the leading causes of premature skin aging, immunosuppression and carcinogenesis. Photoprotection can be achieved by the use of sunscreens and also by systemically administered compounds that fight the deleterious biological effects of UV exposure, or preferably both. In this review, we summarize the current knowledge on the tissue, cellular and molecular mechanisms underlying the photoprotective effect of Polypodium leucotomos fern extract. P. leucotomos blocked the deleterious effect of UV irradiation both in vivo and in vitro. The molecular basis of photoprotection relies on its ability to inhibit free radical generation, prevent photodecomposition of both endogenous photoprotective molecules and DNA, and prevent UV-induced cell death. Its complete loss of toxicity combined with its multifactor protection makes it a valuable tool not only for direct photoprotection, but also as an efficacious adjuvant to phototherapy of various skin diseases.

Drugs Today (Barc). 2007 Jul;43(7):475-85

The antioxidant action of Polypodium leucotomos extract and kojic acid: reactions with reactive oxygen species.

Two natural products Polypodium leucotomos extract (PL) and kojic acid (KA) were tested for their ability to scavenge reactive oxygen species (.OH,.O2-, H2O2, 1O2) in phosphate buffer. Hydroxyl radicals were generated by the Fenton reaction, and the rate constants of scavenging were 1.6 x 10(9) M-1 s-1 for KA and 1.0 x 10(9) M-1 s-1 for PL, similar to that of ethanol (1.4 x 10(9) M-1 s-1). With superoxide anions generated by the xanthine/hypoxanthine system, KA and PL (0.2-1.0 mg/ml) inhibited.O2-dependent reduction of nitroblue tetrazolium by up to 30 and 31%, respectively. In the detection of 1O2 by rose bengal irradiation, PL at 1.0 mg/ml quenched singlet oxygen by 43% relative to azide and KA by 36%. The present study demonstrates that PL showed an antioxidant effect, scavenging three of four reactive oxygen species tested here. Unlike KA, PL did not significantly scavenge hydrogen peroxide.

Braz J Med Biol Res. 2001 Nov;34(11):1487-94

Polypodium leucotomos extract inhibits trans-urocanic acid photoisomerization and photodecomposition.

In this report, we demonstrate a possible molecular mechanism by which a hydrophilic extract of the leaves of the fern Polypodium leucotomos (Fernblock, PL) blocks ultraviolet (UV)-induced skin photodamage. The extract inhibits UVA and UVB light induced photoisomerization of trans-urocanic acid (t-UCA), a common photoreceptor located in the stratum corneum, and also blocks its photodecomposition in the presence of oxidizing reagents such as H2O2, and titanium dioxide (TiO2). PL protects in vitro human fibroblasts from UV-induced death as well. These results suggest the potential of employing the PL extract as a component of sunscreen moistures in order to prevent photodecomposition of t-UCA, to inhibit UV-induced deleterious effects of TiO2 and to protect skin cells and endogenous molecules directly involved in skin immunosurveillance.

J Photochem Photobiol B. 2006 Mar 1;82(3):173-9

Apoptosis and pathogenesis of melanoma and nonmelanoma skin cancer.

Skin cancers, i.e., basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, belong to the most frequent tumors. Their formation is based on constitutional and/or inherited factors usually combined with environmental factors, mainly UV-irradiation through long term sun exposure. UV-light can randomly induce DNA damage in keratinocytes, but it can also mutate genes essential for control and surveillance in the skin epidermis. Various repair and safety mechanisms exist to maintain the integrity of the skin epidermis. For example, UV-light damaged DNA is repaired and if this is not possible, the DNA damaged cells are eliminated by apoptosis (sunburn cells). This occurs under the control of the p53 suppressor gene. Fas-ligand (FasL), a member of the tumor necrosis superfamily, which is preferentially expressed in the basal layer of the skin epidermis, is a key surveillance molecule involved in the elimination of sunburn cells, but also in the prevention of cell transformation. However, UV light exposure downregulates FasL expression in keratinocytes and melanocytes leading to the loss of its sensor function. This increases the risk that transformed cells are not eliminated anymore. Moreover, important control and surveillance genes can also be directly affected by UV-light. Mutation in the p53 gene is the starting point for the formation of SCC and some forms of BCC. Other BCCs originate through UV light mediated mutations of genes of the hedgehog signaling pathway which are essential for the maintainance of cell growth and differentiation. The transcription factor Gli2 plays a key role within this pathway, indeed, Gli2 is responsible for the marked apoptosis resistance of the BCCs. The formation of malignant melanoma is very complex. Melanocytes form nevi and from the nevi melanoma can develop through mutations in various genes. Once the keratinocytes or melanocytes have been transformed they re-express FasL which may allow the expanding tumor to evade the attack of immune effector cells. FasL which is involved in immune evasion or genes which govern the apoptosis resistance, e.g., Gli2 could therefore be prime targets to prevent tumor formation and growth. Attempts to silence these genes by RNA interference using gene specific short interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) have been functionally successful not only in tissue cultures and tumor tissues, but also in a mouse model. Thus, siRNAs and/or shRNAs may become a novel and promising approach to treat skin cancers at an early stage.

Adv Exp Med Biol. 2008;624:283-95

Photoageing: mechanism, prevention and therapy.

Photoageing is the superposition of chronic ultraviolet (UV)-induced damage on intrinsic ageing and accounts for most age-associated changes in skin appearance. It is triggered by receptor-initiated signalling, mitochondrial damage, protein oxidation and telomere-based DNA damage responses. Photodamaged skin displays variable epidermal thickness, dermal elastosis, decreased/fragmented collagen, increased matrix-degrading metalloproteinases, inflammatory infiltrates and vessel ectasia. The development of cosmetically pleasing sunscreens that protect against both UVA and UVB irradiation as well as products such as tretinoin that antagonize the UV signalling pathways leading to photoageing are major steps forward in preventing and reversing photoageing. Improved understanding of the skin’s innate UV protective mechanisms has also given rise to several novel treatment concepts that promise to revolutionize this field within the coming decade. Such advances should not only allow for the improved appearance of skin in middle age and beyond, but also greatly reduce the accompanying burden of skin cancer.

Br J Dermatol. 2007 Nov;157(5):874-87

How best to halt and/or revert UV-induced skin ageing: strategies, facts and fiction.

Once considered mainly a cosmetic issue, photoageing research has long moved to the forefront of investigative dermatology. Besides obvious market pressures, increasing insight into the mechanistic overlap between UV-induced skin cancer and UV-induced skin ageing has contributed to this development. Also, as strategies that work to antagonize intrinsic skin ageing/senescence may also be exploited against photoageing (and vice versa!), it has become an important skin research challenge to dissect both the differences and the overlap mechanisms between these interwined, yet distinct phenomena. Finally, the current surge in putative ‘antiageing’ products, devices, and strategies - too many of which boldly promise to fight and/or repair the perils that come along with a lifetime spent in the sun in the absence of convincing evidence of efficacy - makes it particularly pertinent to critically review the available evidence to support often made antiageing claims. The current CONTROVERSIES feature, therefore, aimed to provide both guidance through, and critical voices in, the antiageing circus. Here, a panel of experts defines relevant key problems, points the uninaugurated to intriguing aspects of photoageing that one may not have considered before, highlights promising strategies for how best to halt and/or revert it, and spiritedly debates some controversially discussed approaches.

Exp Dermatol. 2008 Mar;17(3):228-40