Carotenoids

β-carotene, astaxanthin and lycopene are all carotenoids, which are organic pigments found in plants, some bacteria, fungi and algae81, 97. They are all important antioxidants known to have photoprotective properties at both the epidermal and dermal levels. Human skin is especially rich in β-carotene and lycopene, with β-carotene being the most prominent98. It is mostly found in carrots, sweet potatoes and pumpkin. Oral supplementation of β-carotene and lycopene has shown that it protects against UV radiation-induced erythema99, 100. Studies have shown that oral supplementation of β-carotene should be longer than 7 weeks, and greater than 12 mg/d, in order to be effective99, 101, 102.

Astaxanthin is abundantly found in microalgae, yeast, shrimp, crayfish and crustaceans. It gives the salmon and cooked shellfish their red colour97. Studies have shown that astaxanthin improves the skin’s elasticity, roughness, moisture content, and reduces wrinkles103–105. In vitro, it protects the dermal layer from singlet oxygen damage, ultimately leading to collagen recovery106. Astanxanthin interferes with MMP-1 and skin fibroblast elastase expression107. This suggests that it minimises skin wrinkling and sagging induced by UVA radiation. Furthermore, studies indicate that the combination of oral supplementation (6 mg/dl) and topical administration might be more effective in preventing skin ageing108.

Polyphenols

Polyphenols, among others, include black and green tea, genistein, resveratol, ellagic acid and grape seed proanthocyanidins. Their importance in anti-skin ageing research has increased as daily oral intake can be as high as 1 g/d, which is higher than most other antioxidants109, 110. Laboratory studies suggest that when the ingestion of polyphenols is combined with topical application of sunscreen, they have the capacity of preventing the adverse effects of UV radiation111. Recent studies have also shown that black and green tea extracts, when formulated into dermal gel and applied locally on the skin, provide protection against UV-induced erythema112, 113. They are promising candidates to protect the skin from the harmful effects of UV radiation, in particular erythema and premature skin ageing112, 113.

In a pilot study, 30 post-menopausal women were given 100 mg soy extract rich in isoflavones per day. After 6 months of treatment, 23 had increased epidermal thickness, 25 had increased collagen content, and 22 had an increased number of elastic fibres114. It has been shown that the combination of genistein and daidzein might be more effective in protecting against the adverse effects of UV radiation115. Non-toxic ellagic acid can prevent collagen breakdown in UVB radiated skin cells, by blocking MMP production116. In the same study, topical application of ellagic acid (10 μmol/l) prevented UVB-radiated inflammatory responses in hairless mice, leading to the hypothesis that ellagic acid, which is rich in berries, is a promising treatment strategy for preventing skin wrinkling and the UVB effects that lead to photoageing116.

Resveratrol, which is abundant in the skin of grapes, is considered another important antioxidant for preventing skin ageing117. Studies have shown that it prevents UV-induced photoageing by activating sirtiun 1 (SIRT1)118 and prevents pigmentation by inhibiting tyrosine kinase activity and maturation119. In vitro experiments on skin fibroblasts showed that there was a dose-dependent decrease in collagenase activity and increase in cell proliferation with resveratrol120. The major antioxidant in green tea, epigallocatechin-3-gallate (EGCG), is another important polyphenol. It decreases the production of MMP-1, MMP-8 and MMP-13 in a dose-dependent manner121. Oral administration of EGCG for 8 weeks in hairless rats increases the minimal erythema dose for UV radiation and helps in delaying the UV effects of photoageing122.

Anti-advanced glycation end-product strategies

Vitamin C, E, B3, zinc and manganese have shown to inhibit the in vitro glycation of albumin123. Certain spices and herbs, such as ginger, cinnamon and cloves, have also been found to do the same124. ALA, owing to its antioxidant action, was shown to reverse glycated collagen in rats125. Another compound that has also showed promising results in inhibiting AGEs is EGCG126.

Growth factors and cytokines

Growth factors regulate cell proliferation, chemotaxis and formation of the ECM. They can be derived from a number of sources, including humans, animals, microbes, yeasts and plants127. Human growth factors have been shown to provide some repair of photodamaged skin, but concerns about tumorigenesis have been expressed128–130. An effective animal-derived growth factor, from the snail Cryptomphalus aspersa (SCA), was discovered to have the ability to regenerate damaged skin, and eventually it was processed into a topical product for aesthetic use131. A double-blind, randomised trial in 25 patients, showed that the application of 8% SCA emulsion and 40% SCA liquid serum resulted in significant improvement of periocular rhytides and skin texture when compared with the placebo131.

Studies have shown that the combination of growth factors and anti-inflammatory cytokines when applied topically reduces the damaging effects of photoaged skin132, 133. A placebo-controlled trial showed a significant decrease in skin roughness and an improvement in hydration, smoothness and elasticity, when applying a mixture of growth factors and cytokines twice daily for 2 months134, 135. In another study, a synthetic human-like epidermal growth factor made from barley was topically applied twice daily for 3 months in 29 females aged 39–75 years. The results showed a statistically significant improvement in wrinkles and pore size136.

The use of autologous platelet-rich plasma (PRP) has also gained attention in skin anti-ageing interventions because it has been shown to rejuvenate the skin by activating fibroblasts, leading to increased synthesis of collagen and other matrix components137, 138. PRP is derived from fresh whole blood containing a high concentration of platelets with an abundance of growth factors secreted139. A study on three groups of UVB radiated mice showed that the PRP injected group had more wrinkle reduction and dermal thickening than the other two groups (non-treated group and saline-treated group)139. Another study indicates that PRP enhanced with white blood cells leads to more tissue augmentation than PRP alone140.