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Abstract: 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.
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Defining ageing as a disease and then trying to cure it is unscientific and misguided (1). Fortunately or unfortunately, this is hardly the general perception, as far as the doctors and patients of today are concerned. We live in an era where the booming cosmetology and pharmaceutical industry are thriving on the very premise that ageing is indeed a disease.
Skin ageing can be divided into intrinsic ageing and photoageing (2). The initial molecular events that lead to most of the histological and clinical manifestations of chronic photodamage of the skin are DNA photodamage and UV-generated reactive oxygen species, at which most therapies are targeted. The knowledge of the UV-absorbing chromophores in the skin and of the molecular mechanisms leading to the unwanted effects of sun exposure provides the scientific basis for the development of novel strategies for the prevention and repair of photoageing.
We live in an era of exhibitionism, which drives the need for sun protection, and inadvertently, the need for antiageing therapies as well. Sunscreens rather than clothing are a natural answer to the prevention of UV-induced skin damage. It is also cost effective and acceptable, unlike many dermatologist-based therapies. There is evidence to suggest that, apart from their preventive role, sunscreens may in fact permit photodamaged skin to repair itself (3). What can be tricky is that the internationally accepted standard of measuring the efficacy of sunscreens – sun protection factor (SPF) – may be a poor indicator of a sunscreen’s effectiveness in preventing photodamage, a fact unknown to most over-the-counter buyers. Most sunscreens are designed to prevent UVB-induced sunburn; even broad-spectrum sunscreens boasting of a high SPF (>20) may allow significant amounts of UVA-induced free radical generation to occur. Sunscreens with better UVA blocking ability (zinc oxide, titanium dioxide) (4) are probably more effective in preventing UV-induced photodamage, and should be a necessary part of the arsenal against photoageing, especially in persons with lighter skin types engaging in prolonged outdoor/leisure activities. Unless the objective of sun exposure is deliberate tanning (and inadvertent photoageing), appropriate clothing, hats and other protective devices are a necessary adjunct to photoprotection.
The most widely studied and proven pharmacological therapy for revitalization of photoaged skin are retinoids, particularly tretinoin (2,5). There is compelling evidence to indicate that sun exposure may induce a state of functional retinol deficiency in photoaged skin, with topically applied tretinoin being able to both prevent and repair collagen damaged by sun exposure through inhibition of matrix metalloproteinases and stimulation of procollagen synthesis. However, as is the case with many good things in life, it comes with a price tag – the issue of retinoid dermatitis, manifesting as erythema, scaling and pruritus at the site of application – an unwelcome side effect in most patients. Is the irritancy of tretinoin really the hidden ace up its sleeve? Ongoing research on newer receptor-selective retinoids (seletinoid G) will probably provide interesting answers to these questions (6).
Antioxidant formulations deserve a place at the heart of any antiageing regimen as they target the very basis of ageing – reactive oxygen species. A number of topical and systemic formulations have been studied and found to be effective, including topical vitamin C (7) and oral ones containing vitamins (E, C and carotenoids), minerals (selenium) and other substances (8,9).
A number of botanical antioxidants (10) have recently been investigated, with promising results with regard to polyphenols (in green tea), (11,12) soy isoflavones – genistein and daidzein (13), anthocyanidins and tannins (pomegranate) and resveratrol (skin and seeds of grapes, nuts, fruits and red wine). Some lesser known botanical agents with varying modes of action also deserve a mention here – date palm kernel (14), gingko biloba (15), kojic acid (2), pycnogenol (16) and lemon oil (17). Many over-the-counter products contain some of these compounds, in addition to fruit alpha hydroxy acids, but their stability, and hence, efficacy is questionable.
An interesting concept known as hormesis has recently attracted attention in the field of antiageing research (1). The theory behind the approach – that low doses of toxic or harmful substances have a protective effect – is known as hormesis. It makes use of the body’s intrinsic capacity for self-maintenance and repair, by exposing cells and organisms to brief periods of stress. The paradigm for hormesis is exercise, an activity that is both stressful and damaging due to the production of free radicals, acids, stress hormones and tissue damage. However, as an inducer of repair and maintenance processes, the hormetic effect of this strenuous activity has a wide range of health-promoting effects, including slowing down of ageing.
Most present-day dermatologist based therapies/procedures, which may be regarded as a form of tertiary prevention, are targeted at some kind of controlled therapeutic dermal damage and regeneration of new collagen (18–20). The costs of many of these therapies, including the infamous ‘botox’, are prohibitive – ageing may not be good for your health, but it certainly is good for business.
Some techniques, which may not have good marketing potential (simply because they defy attractive packaging and sales gimmicks), are a healthy balanced diet, avoidance of smoking, a good skin care regimen and regular exercise, coupled with sun protection in those with sensitive skin and outdoor lifestyles. The antiageing industry is a multibillion dollar enterprise, but there are still some things money cannot buy (at least not yet!).