The Secrets of ANTI Major Aging Signs Vitamin(1) in Restored and Increased Collagen Production in Responsible for Wrinkle Effacement, Scientists Revealed

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, protect the skin matrix through inhibition of enzymatic degradation by promoting collagen synthesis in skin elasticity and tightness(a). 

Other suggested that reactive oxygen species induced domino effects in production of more free radicals, which can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of antioxidant system, leading to injuries and damage regulation pathways of skin, in initiated skin aging 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 in vision health and antioxidant scavenging and 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 associate to reduction of 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 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 increase of cytokeratin 16 expression which is essential in skin healing and maintenance, without causing the desquamation and erythema(4).

 In a vivo study to assess major aging signs and performing three-dimensional profilometry and digital imaging during a 9-month double-blind placebo-control involving 48 volunteers, researchers found that topical application of a ROL-containing product not only improves all major aging signs including wrinkles under the eyes, fine lines and tone evenness, but also promotes 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  superior effects in compared to retinol on collagen synthesis.

Retinyl retinoate 1 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 in increased collagen production in responsible for wrinkle effacement.

Others insisted that 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,  play an important role in prevention and treatment of some diseases through antioxidant effects.

Nutrition rich in carotenoids is best known to prevent cell damage, premature skin aging, and skin cancer(10). 

Carotenoids  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). 

In free radicals cause of premature skin aging and lead to immunosuppression and the formation of skin diseases, scientists indicated that administration of carotenoids may interact with free radicals to  protective system against destructive skin(13). 

Other studies 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 induced reactive oxygen species (ROS) in development of premature skin aging, injection of carotenoid-tablets combined with placebo-cream in induced less carotenoid accumulation than carotenoid-tablets alone(15).

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. 

Application of 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 in premature aging. 

In skin of streptozotocin (STZ)-induced type 1 diabetic rats, researchers showed that  vitamin A treated mice  improves the production of collagen in dermis, cell growth and 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.


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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)