As a natural part of the human process, ageing cannot be avoided. But let’s be honest, if we could slow it down, we would – right? Truth be told, radiant, glowing skin is something we aspire to at all ages, but maintaining it through the years? Now that is impressive. Some might even say bestowed only upon those with ‘good genes’.
As it turns out, genetics are much lower on the list of factors influencing our skin’s destiny than previously assumed. The beauty industry has been quick to respond to this; providing a plethora of lotions and potions – many of which use nutrients as their active ingredients, but can also include an abundance of parabens and other harsh chemicals. We now understand that internal and external factors influence our outward appearance. While we are limited in how much we can control factors in our external environment, such as UV exposure and pollution, by understanding the underlying mechanisms of skin ageing, we can make sure that we have all we need to mitigate our body’s internal ageing processes.
As the body’s largest organ, the skin primarily functions as a permeable barrier; both keeping toxins out and releasing them from the body via sweating. When our toxic-load is high, perhaps as a result of impaired detoxification or excess inflammation, signs can often be reflected in the skin as dullness, blemishes and premature wrinkling.
Luckily, there are several nutrient-led mechanisms which have been shown to mitigate common age-related skin issues such as collagen degradation, photo-ageing and the appearance of fine lines and wrinkles. Antioxidants such as carotenoids, polyphenols, flavonoids and vitamins, as well as essential fats, proteins and certain bacteria have been widely referred to as agents capable of promoting skin health and beauty. In this article, we will explore exactly why that is.
Types of skin ageing
The measure of skin ageing consists of two independent, clinically and biologically distinct processes:1
- Intrinsic skin ageing: this is part of the chronological ageing cycle, which affects skin in the same pattern as all internal organs are affected.2 The rate of intrinsic ageing is primarily influenced by genetic and/or metabolic factors
- Extrinsic skin ageing: this represents the external or visual aspect of ageing skin. The rate of extrinsic skin ageing can be determined by a host of factors, including environmental influences such as pollution or chronic sun exposure and ultraviolet (UV) irradiation; or smoking, sleep deprivation and poor nutrition. UVB exposure mostly affects the epidermis, while UVA can cause DNA mutations and destroy collagen, elastin, proteoglycans and other dermal cellular structures.
These ageing processes are accompanied by changes in the cutaneous skin cells, such as functional and structural changes in collagen, elastin and proteoglycan levels required to keep the skin strong, tight and hydrated. Experts largely agree that prevention is key when it comes to safe-guarding against extrinsic skin ageing. Living a healthy, low stress lifestyle which includes an unprocessed, wholefoods diet and regular exercise will go a long way in mitigating the rate of ageing. However, with that said, there are certain compounds which may have a targeted anti-ageing effect on the skin.
What are the key molecular mechanisms of skin ageing?
In order to understand how certain compounds can mitigate the ageing process, we must first look at the key mechanisms responsible for cellular ageing. While many models have been proposed to explain the molecular basis for skin ageing, the following play a central role:3
– Oxidative stress: occurs when there is an imbalance between production of free radicals (reactive oxygen species, ROS) and the ability of the body to counteract or detoxify their harmful effects using antioxidants. ROS play a critical role in alterations of the dermal extracellular matrix, both in the case of intrinsic and photo(extrinsic)ageing. They repress collagen production resulting in the decreased levels of collagen observed in photo-aged skin
– DNA Damage: persistent exposure to UV radiation increases DNA damage and mutations, which can lead to premature ageing.4 More specifically, the following can occur:
- Telomere shortening: telomeres act as buffers at the end of our chromosomes, protecting our genes from damage during cell division. UV radiation leads to excessive ROS production, resulting in telomere mutations and further cell death or senescence5
- microRNA (miRNA) regulation: in genetics, a miRNA is a form of single-stranded RNA which regulates the expression of other genes. In the skin, miRNA plays a key role in regulating the balance between a cell’s proliferative capacity (ability to regenerate injured cells and tissues) and replicative senescence (how many times a cell can divide). Fibroblasts, which are responsible for collagen synthesis and structural tissue framework in the skin also show increased miRNA activity with age6
- Advanced glycation end products (AGEs): glycation is involved in both intrinsic and extrinsic ageing. AGEs are proteins or lipids which become glycated as a result of exposure to sugars; accumulation of these can result in tissue stiffening and reduced elasticity7
- Genetic mutation: there is an extremely rare genetic mutation which can cause progeria, a type of premature ageing, which often results in: i) an accelerated skin ageing phenotype, including skin atrophy and sclerosis; ii) poikiloderma (a condition which causes skin discolouration and breakdown) and iii) alopecia, thinning, and greying of the hair8
– Inflammaging: chronic, low grade inflammation is recognised as a major characteristic of the ageing process and is often referred to as ‘inflammaging’.9 It plays a role in the initiation and progression of age-related diseases such as type II diabetes, Alzheimer’s disease, cardiovascular disease and skin ageing.10
Key nutrient considerations for mitigating skin ageing
Now that we know how skin ageing occurs and the key factors of influence, let’s look at the agents which research has shown may mitigate these effects and slow the natural skin ageing cycle:
Vitamin C: acts as a co-factor for the enzymes responsible for the stabilisation and cross-linking of collagen molecules. With sunscreen capable of blocking only 55% of the free radicals produced by UV exposure, antioxidants like vitamin C are essential for neutralising the ROS formed due to UV exposure. A double-blind, placebo-controlled study on 10 subjects using 10% topical vitamin C over a 12-week period showed a statistically significant reduction in photo-aged scores and improvement in wrinkling in vitamin C-treated patients compared to placebo.11
Tocopherols and tocotrienols (vitamin E): the natural vitamin E complex comprises a group of 8 compounds called tocopherols and tocotrienols. Vitamin E is a strong anti-inflammatory agent in the skin, with its primary photoprotective role being to prevent damage caused by free radicals and ROS.
While vitamins E and C can provide photoprotection alone, they work best in conjunction. For example, vitamin E quadruples the action of vitamin C. Hydrophilic vitamin C helps to regenerate vitamin E, a lipophilic antioxidant. Together, these antioxidant vitamins protect both the water and lipid compartments of the cell. When working synergistically, they limit chronic UV damage by reducing both cell apoptosis (cell death) and thymine dimer formation (this is where two adjacent thymine bases in DNA become abnormally bonded).12 As well as vitamin C, CoQ10 and glutathione can also recycle vitamin E.
Vitamin D: this well-known vitamin is in fact a prohormone; a substance which the body converts to a hormone. The skin, as the primary site of vitamin D production, is one of the central tissues in the prohormone vitamin D endocrine system. It contains a cholesterol-like substance called provitamin D3 which reacts with UVB light to form vitamin D3. Several studies have demonstrated the protective effect of calcitriol (the hormonally active metabolite of vitamin D) against UVB-induced skin damage and carcinogenesis.13,14 Research conducted by Chang et al., further suggests a strong association between skin ageing and levels of calcifediol, another precursor of vitamin D.15 This makes sense considering the broad variety of vitamin D’s physiological functions. Not only does it protect skin cells from UV-induced cell death and apoptosis, but it inhibits the activation of stress-activated protein kinases (controls cellular survival, differentiation and apoptosis),14 and suppresses production of the proinflammatory cytokine, IL-6.
The capacity of the skin to produce vitamin D declines with age, with concentrations of 7-dehydrocholesterol—a vitamin D3 precursor—declining by approximately 50% between the ages of 20-80.16 Vitamin D status is also heavily influenced by the weather, with one in five people in the UK, having low serum vitamin D levels.17
Skin cancer is also the fifth most common form of cancer in females. Studies have indicated that oral vitamin D treatment demonstrates clear skin cancer prevention capabilities, with links to anti-ageing effects.18,19
Carotenoids refer to vitamin A derivatives (such as beta-carotene), astaxanthin, lycopene and retinol; all highly effective antioxidants which hold distinct photoprotective properties. In fact, in comparison to other antioxidants such as lutein and zeaxanthin, the human skin is relatively enriched with carotenoids like beta-carotene and lycopene, possibly reflecting a more specific photoprotective function.20
- Beta-carotene: while its primary role is its provitamin-A activity, beta-carotene is an endogenous photoprotector, and its efficacy to prevent UV-induced erythema formation has been demonstrated in various studies.21,22 It also significantly reduces the rate of mitochondrial mutation in human dermal fibroblasts after UV irradiation23
- Astaxanthin: found in microalgae, yeast, salmon, trout, krill, shrimp, crayfish and crustacea. Algal extract containing 14% astaxanthin was found to prevent UVA-induced alterations in cellular superoxide dismutase activity (an antioxidant enzyme) and the subsequent decreases in cellular glutathione content.24 It also shows pronounced photoprotective effects and an ability to counteract UVA-induced alterations such as skin sagging or wrinkling25,26
- Lycopene: while it has no vitamin A activity, lycopene is technically a carotenoid. Significant amounts of lycopene are destroyed when skin is exposed to UV light stress, suggesting a role in mitigating oxidative damage in skin tissues27
- Retinol: a fat-soluble, unsaturated isoprenoid, retinol cannot be synthesised by the body. There are two retinoid receptors in the skin, where retinol and its metabolites (retinaldehyde and retinoic acid) act. It has an essential role in the growth, differentiation and maintenance of epithelial (skin) tissues
Botanical antioxidants: polyphenols, anthocyanosides & isoflavones
Over the last decade, polyphenols have become a central feature in anti-ageing research. Natural polyphenols, anthocyanosides or flavonoids are not only plant pigments, but also powerful antioxidants which protect plants against disease. With potent antioxidant capabilities, increasing research is demonstrating their protective affects against UV-induced skin inflammation, oxidative stress and DNA damage.28
- Resveratrol: this small polyphenol found in the skin of red grapes, fruits and red wine is often cited for its potential anti-carcinogenic effects; attributable to its ability to scavenge free-radicals29 and induce anti-inflammatory effects.30 It has a demonstrated ability to protect against the depletion of endogenous antioxidant defence enzymes, suppress lipid and protein oxidation and inhibit apoptosis31
- Soybean isoflavones: also known as a phytoestrogen due to its structural similarity to oestrogen. Mice fed soy isoflavones showed significantly less wrinkling in their UV-irradiated skin versus controls.32 Interestingly, collagen deposition was also increased as a result of the dietary isoflavones. Similar results have been demonstrated in human trials, with significant decreases in fine facial wrinkles after 12 weeks of soy isoflavone supplementation.33
- Propolis: a 2017 study in the Journal of Biomedicine and Pharmacotherapy revealed the strong anti-photoageing potential of propolis extract.34 It not only demonstrated free radical scavenging activity and an increased viability in UVB-irradiated human fibroblast skin cells, but also increased the expression of two longevity-associated genes: FOXO3A and NGF.
- Curcumin: predominantly extracted from turmeric spice and a member of the ginger family, curcumin shows a pronounced ability to attenuate oxidative stress and suppress inflammation.35 In human fibroblasts, curcumin induced cellular antioxidant defences.36
- Cocoa flavanols: these are naturally occurring antioxidant and anti-inflammatory compounds. A double-blind in vivo study looked at the impact of cocoa flavanols on individuals minimal erythema dose (MED, sensitivity to the sun) and discovered that after 12-weeks of cocoa flavonol intake, participants’ MED more than doubled, suggesting significant photoprotection.37 Cocoa flavanol consumption also increased dermal blood flow and oxygen which may help to reduce accelerated ageing.38
- Anthocyanides (e.g. found in bilberries): have potent antioxidant and photoprotective activity. These have also been found to minimise UV-induced erythema or sunburn.39
Ubiquinol (coenzyme Q10)
CoQ10 is a fat-soluble, vitamin-like substance; mainly stored within the body’s adipose tissues. While it has a plethora of functions within the body, in the skin, it is primarily found in the epidermis where it forms part of the initial barrier to oxidant assault in combination with other enzymatic and non-enzymatic substances.40 In animal studies supplementation resulted in elevation of CoQ homologs in tissues and their mitochondria, causing a selective decrease in protein oxidative damage and an increase in antioxidative potential.41
MSM is a naturally occurring organosulphur compound. Consumption of MSM may help to reduce wrinkles by protecting extracellular matrix proteins such as collagen from damage and degradation. It does this by inhibiting the NF-kB pro-inflammatory signalling pathway, thus inducing an anti-inflammatory effect.42 Through this mechanism, it also inhibits the expression of the enzymes and cytokines involved in ROS production.
Four weeks of oral supplementation of collagen hydrolysate increased elasticity of the skin in middle-aged women. A skin moisturising effect was also observed in women over 50 years of age.43 Animal studies demonstrated similar findings,44 where oral collagen peptides induced an increase in fibroblast density and formation of dermal collagen fibrils in piglet skin, while suppressing UVB-induced decreases in hydration, epidermal hypertrophy and type 1 collagen in mice.45
Omega-3 fatty acids
Eicosapentaenoic acid (EPA) and other omega-3 fatty acids reduced levels of proinflammatory mediators, reduced DNA damage and strand breaks and increased sunburn threshold (thus reducing the likelihood of sun damage), when taken in high doses of between 4-10g/d.46,47
In an effort to find alternatives to antibiotic skin treatment, probiotics are emerging as a viable therapy. Oral administration of Bifidobacterium breve prevented UV-induced transepidermal water loss (loss of moisture from the skin which can make appearance of fine lines and wrinkles more pronounced) compared to mice receiving placebo. Additionally, the UV-induced increase in hydrogen peroxide levels, oxidation of proteins and xanthine oxidase in the skin was supressed,48 suggesting an ability to at least partially alleviate UV-induced barrier changes and oxidative stress in the skin. Lactobacillus plantarum preserved procollagen expression in human fibroblasts. Oral administration of L. plantarum reduced the number and depth of wrinkles in hairless mice.49
- As the body’s largest organ, the skin primarily functions as a permeable barrier; both keeping toxins out and releasing them from the body via sweating.
- When our toxic-load is high, perhaps as a result of impaired detoxification or excess inflammation, signs can often be reflected in the skin, such as with dullness, blemishes and premature wrinkling.
- There are several nutrient-led mechanisms which have been shown to mitigate common age-related skin issues such as collagen degradation, photo-ageing and the appearance of fine lines and wrinkles.
- There are two measures of skin ageing: intrinsic (from within the body associated with metabolism and genes) and extrinsic (from the external environment i.e. pollution, sun damage, diet and lifestyle factors).
- The key molecular mechanisms of skin ageing include oxidative stress, DNA damage and inflammaging; a chronic, low grade inflammation recognised as a major part of the ageing process.
- Key nutrients for ageing skin include vitamins A, E and D; beta-carotene, lycopene, retinol and astaxanthin.
- Botanical antioxidants such as resveratrol, soy isoflavones, propolis and curcumin have become a central feature in anti-ageing research, with protective effects observed against UV-induced skin inflammation, oxidative stress and DNA damage.
- In the skin, CoQ10 forms part of the initial skin barrier to oxidant assault.
- Both animal and human studies have found that oral supplementation of collagen peptides increased elasticity and hydration of the skin.
- Oral consumption of omega-3 fatty acids reduced inflammation, DNA strand breakage and increased sunburn threshold.
- The probiotics B. breve and L. plantarum mitigated UV-induced cellular and oxidative damage in the skin.
If you have any questions regarding the topics that have been raised, or any other health matters please do contact me (Tracey) by phone or email at any time.
[email protected], 01684 310099
Tracey Hanley and the Cytoplan Editorial Team
Relevant Cytoplan Products:
CoQ10 Multi – comprehensive multivitamin and mineral, additionally containing CoQ10
Krill, CoQ10 and K2 – comprises krill oil, vitamin K, vitamin D3, CoQ10, resveratrol and lycopene.
Antioxidant (plus CoQ10) – contains 50mg of CoQ10, 4.5mg of beta-carotene, 100mg of vitamin C and 16mg of vitamin E.
Vitamin D3 – available as drops (200-1600IU) or capsules (2,500IU) or high potency with vitamin K (4,000IU plus 100mcg vitamin K).
Vitamin A – vegan-friendly product, containing 5,000IU of retinol palmitate.
Cherry C – 200 mg vitamin C from acerola cherry plus naturally occurring bioflavonoids.
Tocopherol and Tocotrienol Complex (vitamin E) – containing the full spectrum of vitamin E as it occurs in nature; alpha, beta, delta, gamma tocopherol and alpha, beta, delta, gamma tocotrienol.
Phytoshield – a very potent and powerful phyto-antioxidant nutrient formula containing high levels of flavonoids and carotenoids. Each capsule supplies 650mg of mixed flavonoids and 15mg of mixed carotenoids.
Krill Oil – Krill are the most bio-effective natural sources of beneficial omega-3 fatty acids EPA/ DHA. Providing 1000mg krill oil, 100IU vitamin A and 1.5mg astaxanthin.
Acidophilus Plus – a blend of 9 native bacterial strains including B. breve and L. plantarum.
Cell-Active Glutathione – Contains 250mg liposomal glutathione and 50mg resveratrol, along with rosemary extract, gingko biloba, alpha lipoic acid and n-acetyl-l-carnitine.
References available upon request.