18 minute read
CPD: Assessing the Extrinsic Factors of Skin Ageing
Assessing the Extrinsic Factors of Skin Ageing
Dr Nihull Jakharia-Shah, Miss Priyanka Chadha and Miss Lara Watson present the extrinsic factors that accelerate skin ageing
Ageing is universal. However, the physical manifestations of ageing vary greatly between individuals. Skin ageing is typically defined morphologically as the development of wrinkles, uneven texture, pigmentation and telangiectasia.1 The drivers of skin ageing can be classified into intrinsic and extrinsic factors. Intrinsic factors are those that we cannot control, namely our genes, whereas extrinsic factors are modifiable and often environmental, such as those caused by smoking, sun exposure and nutrition.2 Intrinsic ageing is unavoidable but its impact is superimposed by extrinsic factors, thus better understanding and control of extrinsic factors is key to limiting the impact of time on the skin.
Intrinsic factors of skin ageing
The intrinsic factors of skin ageing (i.e. one’s genes) are predetermined. Those of genetically male sex have an increased predisposition to demonstrate the physical signs of skin ageing over their female counterparts.3 A recent meta-analysis has suggested that there is no clear association between skin colour and skin ageing, but variability between different ethnicities has been seen.3 It has been suggested that intrinsic factors contribute more to the development of the signs of ageing than extrinsic factors.4 However, as we cannot yet alter our intrinsic risk, attempts to minimise skin ageing will focus on reducing extrinsic factors. As intrinsic ageing cannot be altered, it is important to note that a degree of skin ageing is inevitable and should be embraced as part of the natural, healthy ageing process.
Extrinsic factors of skin ageing
A number of factors contribute to extrinsic skin ageing, including: sun exposure, smoking, diet, pollution, stress, skincare, weight and sleep.
Sun exposure Sun exposure refers to ultraviolet (UV) radiation-induced damage to the skin. Both UVA and UVB have been implicated in this process, though UVB is thought to play a greater role.5 UV radiation causes direct damage to the DNA of skin cells (keratinocytes, fibroblasts for example) leading to reduced function of the cells and even cell death.6 UV exposure also generates oxygen free-radicals which damage local structures and cells within the skin.7 Free radicals lead to the breakdown of, and a reduction in the production of collagen and elastin in the skin.8 Exposure to UV radiation is the greatest extrinsic contributor to skin ageing.9 Photoageing has been shown to have a greater impact in people of lighter skin types, due to the protective properties of melanin against UV radiation.10 It should also be noted that UV radiation is a carcinogen and exposure is directly linked to increased risk of all types of skin cancer, including malignant melanoma.11
Adequate UV exposure is, however, vital for the production of endogenous vitamin D.12 Vitamin D is directly linked to a number of positive health outcomes.13 Thus, global public health campaigns strongly advise maintenance of adequate vitamin D levels, with supplementation if required. Many foods in the UK are fortified with vitamin D, such as cereal. However, these doses are generally not sufficient to achieve healthy levels without adequate sun exposure and possibly external supplementation.14 The UK NHS advice on sun safety includes the following suggestions: spend time in the shade between 11am and 3pm, make sure you never burn by covering up with suitable clothing and sunglasses and using at least factor 30 sunscreen.15 This advice has inconsistent compliance due to practical difficulties and social behaviours, for example wearing covered clothing during summer months. However, the use of sunscreen is paramount for minimising the ageing effect of UV radiation whilst being socially unrestricted. In order to be effective, a sunscreen of at least SPF 15 is required to adequately protect against UVB (93% protection).16 This should be applied as a thin layer over all sun-exposed areas of skin and reapplied every two to four hours. As the impact of UV radiation on skin ageing has become clearer, the pharmaceutical industry has endeavoured to create sunscreens to cater for all skin types and preferences.
Smoking Not only is smoking the most preventable cause of morbidity and mortality worldwide, it produces a significant damaging effect on the skin.17 Smoking is associated with premature skin ageing, melanoma, oral cancer, acne and psoriasis.18 Smoking leads to the breakdown of collagen and elastin as well as generating harmful free radicals. It alters the intra-cellular matrix, changing the consistency of the skin.19
Figure 1: The effects of sun damage
Figure 2: The presentation of smoker’s lines
The act of smoking also directly causes wrinkles around the mouth, known colloquially as smoker’s lines.20 Smoking has established links to poor wound healing outcomes. This is likely due to damage of microvasculature around wound sites and the deposition of toxins.21 Therefore, in the event of seeking any cosmetic procedure to counteract the effects of ageing, smokers will be prone to poor wound healing and risk worse aesthetic outcomes from the resulting scar. Cognitive behavioural therapy and nicotine replacement therapy are amongst a number of recognised methods to facilitate smoking cessation.22 Help can be sought via the general practitioner and local specialist smoking cessation services.
Diet A number of dietary compounds have been associated with improved skin appearance, however a well-rounded diet is vital for maintaining good physical health across all body systems. Fruits, fatty acids and vegetables have all been associated with reduced appearance of skin ageing.23,24,25 Fatty acids in particular play an important role in the skin barrier and hydration of skin.26 Vitamin A, vitamin C, vitamin D and other compounds believed to have antioxidant properties, such as curcumin, polyphenols and flavonoids are all documented to promote younger looking skin.27,28 Retinoids are vitamin A derivatives and are the most commonly used antiageing drugs. They are proven to regulate genes and the extracellular matrix proteins and they also prevent photodamage.29 Consumption of water is important for cellular function and keeping the skin hydrated. Hydrated skin appears fuller, reducing wrinkles and evening contour.30 Trace elements such as zinc, iron and copper are involved in healthy cell biology and formation of the extracellular matrix. They should be consumed in safe amounts (less than 25mg, 17mg and 10mg per day, respectively).31,32 Alcohol consumption has generally shown to have non-significant associations with skin ageing, however at excessive levels (>40 units per day) the association becomes significant.33 Excessive sugar in the diet has shown to promote inflammation within the skin resulting in long-term damage to cellular structures.34 Advice on diet and alcohol consumption as per the UK government guidelines should be recommended to all patients.35,36 Pollution Skin ageing, in particular dyspigmentation and skin wrinkling, is associated with air pollution. Compounds such as nitrogen dioxide, fossil fuels, second hand smoke, traffic-associated particulate and carbon monoxide have been associated with progressive skin ageing.38 It is documented that molecular interactions between pollutants and UV radiation produce exaggerated damaging effects to the skin, accelerating the ageing process. Ozone, O3, at ground level is a harmful pollutant gas.39 Alongside other molecular (e.g. poly-aromatic hydrocarbons) and particulate matter, a cascade of reactions occur within the skin resulting in the release of reactive oxygen species (free radicals) which damage cellular structures, DNA and matrix proteins, resulting in signs of skin ageing.40 Pollutant matter is also responsible for destruction of the atmospheric ozone layer, exposing us to higher levels of UV radiation, which in turn contributes to skin ageing.41 A rising number of cosmeceutical products contain antioxidants. These active ingredients are aimed at reducing the effect of pollution on the skin. Though few objective trials have been conducted to quantify their effect, anecdotal and theoretical studies all suggest a beneficial effect on skin ageing from the use of topical antioxidant.42,42,44 Finally, engaging with activities to reduce/reverse climate change is important as yet another long-term health measure is detrimentally affected by these changes.
Stress Psychological stress is one of the less researched contributors to skin ageing, though anecdotally the association is well defined. Chronic stress has shown to alter gene regulation, increasing an individual’s vulnerability to ageing.45 This genetic dysregulation causes decreased proliferative capacity and altered biosynthetic activity of cells resulting in a disorganisation of the dermal matrix. Epigenetic studies evaluating DNA methylation patterns seek to identify targets for gene alteration in response to stressful stimuli. Finding these biomarkers will enable quantification of the impact of stress on ageing but also possibly identify targets for future therapies.45 Glucocorticoids, such as cortisol, are known to be released in excess in response to stress. These are likely to be responsible for also triggering adverse physiological responses which contribute to extrinsic and intrinsic (gene-related) ageing.46 Chronic stress is also known to activate and alter other physiological systems, such as the hormonal hypothalamic-pituitary axis, the autonomic nervous system and the immune system. Each of the above lead directly or indirectly to increased susceptibility to the ageing processes.47 Complete avoidance of stress is unattainable; instead, identifying effective coping mechanisms is crucial for maintaining good physical and mental health.
Skincare Skincare routines are highly variable and can utilise a range of products, including medicated preparations. At its simplest level, regular moisturising of skin is an essential activity for maintaining good skin function as well as aesthetic skin. Dry skin leads to disorganised keratin structures and reduced extracellular matrix volume, which creates uneven surfaces and makes skin appear sunken.48 Wrinkle appearances are exaggerated in individuals with
dry skin.49 The list of active compounds that are utilised in skincare products is vast and beyond the scope of this article. However, literature suggests that the hydrating component of moisturisers, such as glycerine or petrolatum, leads to a greater impact on improved skin appearance than the advertised active ingredients.50 The choice between ointment, cream or gel-based moisturisers is individual. Compliance is key, thus, the best choice of product is the one a patient is happy to use consistently. It is important to note that sunscreen also falls into this category of topical skincare and, for reasons covered in the previous section on photodamage, should be a component of every basic skincare regime alongside moisturising.
Body mass index Studies suggest that genes encoding proteins involved in skin structure, blood supply and healing are altered in obese (BMI 35-50) individuals compared to those within the defined healthy range (BMI 18-26).51,52 At both ends of the scale, individuals with underweight BMI (<18) and obesity were shown to be more susceptible to skin infections.53 Infections and the resulting inflammation can cause scarring and permanent damage to the skin structure. This can manifest as signs of aged skin and leave the skin more susceptible to other extrinsic factors. UK government’s advice on weight management, as well as dietary advice referenced above, should be relayed to all patients.54
Sleep Sleep plays an important role in the regulation of a number of physiological systems.55 The biological and physiological mechanisms of its effect on skin ageing are not well documented, however, observational studies suggest that sleep deprivation and poor-quality sleep results in the appearance of less healthy, more aged skin.56,57 Both referenced studies focused on female participants. In the former, a cohort of 20 female participants were subjected to sleep deprivation and photo comparisons were made, with each volunteer acting as their own control, to identify skin changes. Increasing wrinkles, drooping corners of the mouth and hanging eyelids were identified in the sleep deprived group and are also signs consistent with skin ageing.58 The precise quantity of sleep needed for optimal health is likely to vary between individuals but in one study, and anecdotally, a good night’s sleep is defined as eight hours.
Consider the extrinsic factors of ageing
Significantly aged skin is associated with perceived negative aesthetic and health characteristics. Though ageing is a natural phenomenon, there exists a multi-billion pound industry dedicated to preventing and reversing the effects of age on skin. The effects of extrinsic factors can be mitigated, if understood. UV-radiation-induced damage is by far the greatest contributor to extrinsic ageing. Simple steps, such as application of moisturisers containing SPF 15+, can be highly effective in preventing UV damage and maintaining healthy skin. Other significant, modifiable factors include diet, stress and sleep. Pollution is becoming more of a concern but is difficult to alter on an individual basis. Whilst steps to minimise extrinsic factors of skin ageing can reduce the rate of skin ageing, it is important to stress that a degree of ageing (intrinsic) is inevitable and should be embraced. Also, activities to minimise skin ageing should take into context the wider health of an individual such that other body systems are not adversely affected by any interventions.
Dr Nihull Jakharia-Shah is an internal medicine trainee with an interest in dermatology. Dr Jakharia-Shah held a position at Acquisition Aesthetics training academy for four years, gaining exposure to clinical aesthetic practice. Qual: MBBS, BSc(Hons)
Miss Lara Watson is a maxillofacial surgery doctor and a UK key opinion leader for various pharmaceutical companies. She is a director at Acquisition Aesthetics training academy. Qual: BM, BSc (Hons), BMedSci, MRCS(Eng), BDS(Hons)
Miss Priyanka Chadha is a plastic surgery doctor and global key opinion leader. She is a director at Acquisition Aesthetics training academy. Qual: MBBS(Lond), BSc (Hons), DPMSA(Lond), MRCS(Eng), MSc(Lond)
Test your knowledge! Complete the multiple-choice questions and go online to receive your CPD certificate!
Questions
1. Which of these is not an extrinsic factor of skin ageing?
2. Which extrinsic factor is the greatest contributor to skin ageing?
3. Which of the following is not in line with
NHS advice on skin protection from sun exposure?
4. Which dietary component is not associated with improved skin health?
5. Excessive stress can accelerate skin ageing through which of the following mechanisms:
Possible answers
a. UV-radiation exposure b. Genes c. Pollution d. Diet
a. UV-radiation exposure b. Smoking c. Sleep d. BMI
a. Apply regular sunscreen b. Avoid sunlight between 11am and 3pm c. Cover up with suitable clothing and sunglasses d. Encourage gentle burning of skin
a. Excessive alcohol b. Copper c. Vitamin A d. Flavonoids
a. Vitamin D deficiency b. Photodamage c. Excess secretion of glucocorticoids d. Free radical generation
Answers: B,A,D,A,C
VIEW THE REFERENCES ONLINE! WWW.AESTHETICSJOURNAL.COM
Your patients with excess weight have the will. You can offer them the way.
Patients achieved signifi cant and sustained weight loss, in conjunction with reduced calorie intake and increased physical activity, in 1-year and 3-year trials vs placebo 1,2*
Similar to natural glucagon-like peptide-1, Saxenda® works to decrease appetite and thereby reduce food intake3†
This is not a real patient but only an illustration.
This material relates to the adult indication only. Please refer to SmPC for full indication.
Adults: Saxenda® is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adult patients with an initial Body Mass Index (BMI) of ≥ 30 kg/m2 (obesity) or ≥ 27 kg/m2 to < 30 kg/m2 (overweight) in the presence of at least one weight-related comorbidity such as dysglycaemia (pre-diabetes or type 2 diabetes mellitus), hypertension, dyslipidaemia or obstructive sleep apnoea. Treatment with Saxenda® should be discontinued after 12 weeks on the 3.0 mg/day dose if patients have not lost at least 5% of their initial body weight. If you would like to request a visit from a representative please contact us on obesityuk@novonordisk.com For all product related enquiries please contact Novo Nordisk Customer Care Centre on 0800 023 2573.
†The exact mechanism of action of liraglutide is not entirely clear.
Prescribing Information
Please refer to the Saxenda® summary of product characteristics for full information. Saxenda® Liraglutide injection 3 mg. Saxenda® 6 mg/mL solution for injection in a pre-fi lled pen. One pre-fi lled pen contains 18mg liraglutide in 3mL. Indication: Adults: Saxenda® is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adult patients with an initial Body Mass Index (BMI) of ≥ 30 kg/m2 (obesity) or ≥ 27 kg/m2 to < 30 kg/m2 (overweight) in the presence of at least one weight-related comorbidity such as dysglycaemia (pre-diabetes or type 2 diabetes mellitus), hypertension, dyslipidaemia or obstructive sleep apnoea. Adolescents (≥12 years): Saxenda® can be used as an adjunct to a healthy nutrition and increased physical activity for weight management in adolescent patients from the age of 12 years and above with obesity (BMI corresponding to ≥30 kg/m2 for adults by international cut-off points) and body weight above 60 kg. Posology and administration: Saxenda® is for once daily subcutaneous use only. Is administered once daily at any time, independent of meals. It is preferable that Saxenda® is injected around the same time of the day. Recommended starting dose is 0.6 mg once daily. Dose should be increased to 3.0 mg once daily in increments of 0.6 mg with at least one week intervals to improve gastro-intestinal (GI) tolerability. Treatment with Saxenda® in adults should be discontinued after 12 weeks on the 3.0 mg/day dose if patients have not lost at least 5% of their initial body weight. Daily doses higher than 3.0 mg are not recommended. No dose adjustment is required based on age but therapeutic experience in patients ≥75 years is limited and not recommended. No dose adjustment required for patients with mild or moderate renal impairment or mild or moderate hepatic impairment but it should be used with caution. Saxenda® for adolescents from the age of 12 to below 18 years old a similar dose escalation schedule as for adults should be applied. Treatment with Saxenda® in adolescents should be discontinued and re-evaluated if patients have not lost at least 4% of their BMI or BMI z score after 12 weeks on the 3.0mg/day or maximum tolerated dose. Saxenda® is not recommended for use in patients with severe renal impairment including endstage renal disease, or severe hepatic impairment or children below 12 years of age. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special warnings and precautions for use: There is no clinical experience in patients with congestive heart failure New York Heart Association (NYHA) class IV and Saxenda® is not recommended for use in these patients. It is also not recommended in patients with eating disorders or treatment with medicinal products that may cause weight gain. Use of Saxenda® is not recommended in patients with infl ammatory bowel disease and diabetic gastroparesis since it is associated with transient GI adverse reactions including nausea, diarrhoea and vomiting. Acute pancreatitis has been observed with the use of GLP-1 receptor agonists, patients should be informed of the characteristic symptoms. If pancreatitis is suspected, Saxenda® should be discontinued. If acute pancreatitis is confi rmed, Saxenda® should not be restarted. In weight management clinical trials, a higher rate of cholelithiasis and cholecystitis was observed in patients on Saxenda® than those on placebo, therefore patients should be informed of characteristic symptoms. Thyroid adverse events such as goitre have been reported in particular in patients with pre-existing thyroid disease. Saxenda® should be used with caution in patients with thyroid disease. An increase in heart rate was observed in clinical trials. For patients who experience a clinically relevant sustained increase in resting heart rate, treatment with Saxenda® should be discontinued. There is a risk of dehydration in relation to GI side effects associated with GLP-1 receptor agonists. Precautions should be taken to avoid fl uid depletion. Patients with type 2 diabetes mellitus receiving Saxenda® in combination with insulin and/or sulfonylurea may have an increased risk of hypoglycaemia. Episodes of clinically signifi cant hypoglycaemia have been reported in adolescents (≥12 years) treated with liraglutide. Adolescents should be informed about the characteristic symptoms of hypoglycaemia and the appropriate actions. Fertility, pregnancy and lactation: Saxenda® should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Saxenda® should be discontinued. It should not be used during breast-feeding. Undesirable effects: Very common (≥1/10); nausea, vomiting, diarrhoea, constipation, headache. Common (≥1/100 to <1/10); hypoglycaemia, insomnia, dizziness, dysgeusia, dry mouth, dyspepsia, gastritis, gastro-oesophageal refl ux disease, abdominal pain upper, fl atulence, eructation, abdominal distension, cholelithiasis, injection site reactions, asthenia, fatigue, increased lipase, increased amylase. Uncommon (≥1/1,000 to <1/100); dehydration, tachycardia, pancreatitis, cholecystitis, urticaria, malaise, delayed gastric emptying Rare (≥1/10,000 to <1/1,000); anaphylactic reaction, acute renal failure, renal impairment. The Summary of Product Characteristics should be consulted for a full list of side effects.
MA numbers and Basic NHS Price:
NI: EU/1/15/992/003. 5 x 3 ml pre-fi lled pens £196.20. GB: PLGB 04668/0409. 5 x 3 ml pre-fi lled pens £196.20. 3 x 3 ml pre-fi lled pens £117.72. Legal category: POM. Full prescribing information can be obtained from: Novo Nordisk Limited, 3 City Place, Beehive Ring Road, Gatwick, West Sussex, RH6 0PA. Marketing Authorisation Holder: Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark. Date last revised: March 2022
* In the 1 year trial patients taking Saxenda® (n=2487) had a baseline body weight of 106.2 kg. Completers’ (n=2437) mean weight loss at week 56 of treatment was 8.4 kg. Patients taking placebo (n=1244) had a baseline body weight of 106.2 kg. Completers’ (n=1225) mean weight loss at week 56 of treatment was 2.8 kg1, p<0.001. In the 3 year trial Patients taking Saxenda® (n=1505) had a baseline body weight of 107.5 kg. Completers’ (n=1472) mean weight loss at week 160 of treatment was 6.5 kg. Patients taking placebo (n=749) had a baseline body weight of 107.9 kg. Completers’ (n=738) mean weight loss at week 160 of treatment was 2.0kg2, p<0.0001. References: 1. Pi-Sunyer X, Astrup A, Fujioka K, et al; for the SCALE Obesity and Prediabetes NN8022-1839 Study Group. A randomised, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373(1):11-22. 2. le Roux CW, Astrup A, Fujioka K, et al; for the SCALE Obesity and Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. 2017;389(10077):1399-1409. 3. Saxenda® Summary of product characteristics, NI&GB. Bagsvard, Denmark: Novo Nordisk A/S.
