Skin aging in Vitamin A points of view

Kyle J.Norton(Draft Article)

Skin aging is one of most visible ageing process which occurs constantly in our skin organ. According to the Clinical Centre of Nis, certain plant extracts may have the ability to scavenge free radicals, to protect the skin matrix through the inhibition of enzymatic degradation, or to promote collagen synthesis in the skin,  affect skin elasticity and tightness(a). Other suggested that free radicals induced domino effects in production of reactive oxygen species, can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of antioxidant system, leading  injuries damage regulation pathways of skin,  including wrinkles, roughness, appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks(b).
Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.

1. Retinols
Activation of both all-trans retinoic acid and 9-cis retinoic acid in nuclear retinoic acid receptors (RARα, RARβ, and RARγ), may associated to skin aging(1). In chronologically aged and photoaged human skin due to alternation of connective tissue collagen, caused by cysteine-rich protein 61(2) (CCN1, a negative regulator of collagen homeostasis). application of all-trans retinoic acid (RA), the major bioactive form of vitamin A in skin, significantly increased type I procollagen and reduced collagenase (matrix metalloproteinases-1, MMP-1)and suppressed recombinant human CCN1(3).
P-Dodecylaminophenol derived from the synthetic retinoid, in the skin of hairless mice study, exhibited the increased cytokeratin 16 expression which is essential in skin healing and maintenance, without causing the desquamation and erythema(4). In a vivo study in assessing major aging signs and performing three-dimensional profilometry and digital imaging during a 9-month double-blind placebo-control involving 48 volunteers, topical application of a ROL-containing product not only improved all major aging signs including wrinkles under the eyes, fine lines and tone evenness, but also promoted keratinocyte proliferation, induced epidermal thickening and alleviated skin aging signs, without any significant adverse reaction(5). Retinyl retinoate 1, another synthetic version of retinols, showed inhibitory activity against c-Jun than retinol and superior effects on collagen synthesis compared to retinol, and may have the potential to be conveniently used as an additive in cosmetics for prevention and improvement of skin aging and medicines for the treatment of skin troubles(6). Some researchers suggested that topical retinol improves fine wrinkles associated with natural aging, through its effects in induction of glycosaminoglycan, increased collagen production are most likely responsible for wrinkle effacement. Retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance(7). Application of a stabilized 0.1% retinol-containing moisturizer showed the improving lines and wrinkles, pigmentation, elasticity, firmness and overall photodamage(8). N-retinoyl-D-glucosamine, a retinoic acid agonist in the study in comparison with retinol acid, showed the same effective of both in complete disappearance of the wrinkles caused by UVB irradiation probably via RAR transactivation activity, but the synthetic agonist showed no adverse effect in causing skin irritation(9).

2. Carotenoids(beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin) and Retinal Carotenoids, plant pigments, converted to vitamin A after intake, though to play an important role in prevention and treatment of some diseases through it antioxidant effects.
Nutrition rich in carotenoids is best known to prevent cell damage, premature skin aging, and skin cancer(10). It has been reported to possess potent anti-oxidant properties and widely used in the skin care industry either as topically applied agents or oral supplements in an attempt to prolong youthful skin appearance(11)(12). Free radicals cause of premature skin aging and lead to immunosuppression and the formation of skin diseases, administration of carotenoids may interact with free radicals to enhance the protection system against that destructive(13). Other study suggested that Stress factors such as illness, UV and IR radiation of the sun, and smoking and alcohol consumption reduce the concentration of the carotenoids in the skin of that lead to deeper and denser of the furrows and wrinkles(14).
The testing of high doses of sun-emitted UV-radiation induce reactive oxygen species (ROS) as major pro-oxidants thus inducing premature skin aging, showed a positive effect of Carotenoid-tablets combined with placebo-cream in induced less carotenoid accumulation than carotenoid-tablets alone(15) of that suggested that In contrast to topical application, the systemically applied carotenoids are stored in the body fat tissue and slowly released onto the skin surface with sweat and sebum. Retinaldehyde (RAL) showed a significant improvement of wrinkles(forehead wrinkles, nasolabial folds, crow's feet and perioral wrinkles)(16).In fact, deficiency of vitamin A may result of induced premature aging. In skin of streptozotocin (STZ)-induced type 1 diabetic rats, showed over expression of matrix metalloproteinase -2 (MMP-2) and hyaluronidase (HAase) but not on vitamin A treated mice, through promoting the production of collagen in dermis and inducing cell growth and inhibition of epidermal differentiation in skin tissues(17).

Taken altogether, vitamin A and its variants are found to be effective in prevention of skin damage and skin aging caused by over expression of type I procollagen and under expression of collagenase (matrix metalloproteinases-1, MMP-1).
Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.

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References
(a) Skin ageing: natural weapons and strategies by Binic I¹, Lazarevic V, Ljubenovic M, Mojsa J, Sokolovic D.(PubMed)
(b) Phytoconstituents as photoprotective novel cosmetic formulations by Saraf S¹, Kaur CD.(PubMed)
(1)  40 years of topical tretinoin use in review by Baldwin HE¹, Nighland M, Kendall C, Mays DA, Grossman R, Newburger J.(PubMed)
(2) Elevated cysteine-rich 61 mediates aberrant collagen homeostasis in chronologically aged and photoaged human skin by Quan T¹, He T, Shao Y, Lin L, Kang S, Voorhees JJ, Fisher GJ.(PubMed)
(3) Retinoids suppress cysteine-rich protein 61 (CCN1), a negative regulator of collagen homeostasis, in skin equivalent cultures and aged human skin in vivo by Quan T¹, Qin Z, Shao Y, Xu Y, Voorhees JJ, Fisher GJ(PubMed)
(4) Effects of the aminophenol analogue p-Dodecylaminophenol on mouse skin by Takahashi N¹, Fujiu Y(PubMed)
(5) Antiaging action of retinol: from molecular to clinical by Bellemère G¹, Stamatas GN, Bruère V, Bertin C, Issachar N, Oddos T.(PubMed)
(6) Synthesis and in vitro biological activity of retinyl retinoate, a novel hybrid retinoid derivative by Kim H¹, Kim B, Kim H, Um S, Lee J, Ryoo H, Jung H(PubMed)
(7) Improvement of naturally aged skin with vitamin A (retinol) by Kafi R¹, Kwak HS, Schumacher WE, Cho S, Hanft VN, Hamilton TA, King AL, Neal JD, Varani J, Fisher GJ, Voorhees JJ, Kang S.(PubMed)
(8) A stabilized 0.1% retinol facial moisturizer improves the appearance of photodamaged skin in an eight-week, double-blind, vehicle-controlled study by Tucker-Samaras S¹, Zedayko T, Cole C, Miller D, Wallo W, Leyden JJ.(PubMed)
(9) N-retinoyl-D-glucosamine, a new retinoic acid agonist, mediates topical retinoid efficacy with no irritation on photoaged skin by Kambayashi H¹, Odake Y, Takada K, Funasaka Y, Ichihashi M, Kato S(PubMed)
(10) Influence of dietary carotenoids on radical scavenging capacity of the skin and skin lipids by Meinke MC¹, Friedrich A, Tscherch K, Haag SF, Darvin ME, Vollert H, Groth N, Lademann J, Rohn S.(PubMed)
(11) Discovering the link between nutrition and skin aging by Schagen SK¹, Zampeli VA, Makrantonaki E, Zouboulis CC.(PubMed)
(12) The role of nutraceuticals in anti-aging medicine by Vranesić-Bender D.(PubMed)
(13) Interaction between carotenoids and free radicals in human skin by Lademann J¹, Schanzer S, Meinke M, Sterry W, Darvin ME(PubMed)
(14) Carotenoids in human skin by Lademann J¹, Meinke MC, Sterry W, Darvin ME(PubMed)

(15) Dermal carotenoid level and kinetics after topical and systemic administration of antioxidants: enrichment strategies in a controlled in vivo study by Darvin ME¹, Fluhr JW, Schanzer S, Richter H, Patzelt A, Meinke MC, Zastrow L, Golz K, Doucet O, Sterry W, Lademann J(PubMed)
(16) Retinaldehyde/hyaluronic acid fragments: a synergistic association for the management of skin aging by Cordero A¹, Leon-Dorantes G, Pons-Guiraud A, Di Pietro A, Asensi SV, Walkiewicz-Cyraska B, Litvik R, Turlier V, Mery S, Merial-Kieny C(PubMed)
(17) A close relationship between type 1 diabetes and vitamin A-deficiency and matrix metalloproteinase and hyaluronidase activities in skin tissues by Takahashi N¹, Takasu S.(PubMed)