Photoaging affects virtually everyone but few people understand that photoaging involves a number of chemcial alterations in the skin that ultimately produce pigmentation, wrinkles, keratoses and skin cancer. Many clinicians are unaware of the chemical changes that are involved in photoageing and too many mistakenly believe glycolic acid and other Alpha Hydroxy Acids – (AHA) are the best way to treat it. By understanding the mechanism of damage we can learn how to mount a scientific attack on photoageing.
Light consists of a whole spectrum of photons, which are “packets” of energy that vary according to their wavelength. Essentially light enters into the skin and certain wavelengths can damage the skin on the molecular or on the sub-atomic level because of the photon energy. Most people believe that the damage is done only by UV light only, but in fact even green, blue and violet light can damage cells. “Soft” green light damages keratinocytes that then stimulate melanocytes to make more melanin!.
On the molecular level, photon energy is absorbed into the molecule which is then altered. The most important example of this is vitamin A which is extremely sensitive to light. When vitamin A absorbs the energy of photons in the range of about 334 nm then vitamin A activity is lost. There are many other molecules that are damaged in the same way, e.g. vitamin C, B12 etc.
On the sub-atomic level, should a photon strike a vulnerable electron in the outer circuit of an oxygen atom, the electron is cast out of its circuit and the molecule, in its quest for another electron to stabilise atomic relationships, becomes a free radical. That starts up a destructive concatenation of chemical reactions, involving tens of thousands of molecules in a fraction of a second, which may damage cellular structures and DNA.
Chronic damage eventually leads to photoageing. Clearly, we have to know which molecules in skin are damaged by light because that should help us to design a therapeutic regime. It is quite natural to look first at photosensitive molecules found in skin. The first molecules to come to mind are vitamin A and C.
For decades we have known that Vitamin A is vital for healthy skin. Wise and Sulzberger suggested in 1938 that there is a local hypo-vitaminosis A in wrinkled skin[i]. We now know that UV-A rays particularly at 334 nm are responsible for photodecomposition of Retinyl palmitate[ii] (the main form of vitamin A in the skin). UV-A rays are ubiquitous, plentiful and can penetrate through clouds and window panes, so it is easy to understand that retinyl palmitate is easily destroyed every day even in cloudy conditions.. Vitamin A is the one key molecule essential for normal function of all cells of the skin: keratinocytes, melanocytes, Langerhans cells and fibroblasts. Cluver[iii] was a pioneer in recognising that Vitamin A played an essential role in counteracting sun-damage. He showed that every time we go out into sunlight, the photo-sensitive Vitamin A molecule is denatured not merely in the skin, but also in the blood. With time investigations have demonstrated that vitamin A is not only good for ageing skin, but actually essential[iv]. We know that retinyl palmitate specifically protects the DNA from damage and when applied topically in adequate doses can have DNA protective effects to the same extent as a sunscreen SPF 20. Retinol, retinyladehyde and retinoic acid do not give this photo-protective effect and actually make skin photosensitive.[v] Women have an added disadvantage because blood levels of vitamin A drop when they menstruate[vi]. That means that they are more vulnerable to photo-damage.
Ascorbic acid is another molecule that changes its chemical nature after exposure to light, but in this case, the energy of blue light is absorbed into the molecule and ascorbic acid loses its vitamin C effects. Blue light damages keratinocyte DNA and reflexly increases melanin production. Blue light can be toxic to cells. A well known example of this is central retinal degeneration.
Vitamin A has a vast array of physiological actions on the cells of the skin but is not (for practical purposes) an antioxidant, whereas vitamin C has some physiological role in the DNA of the fibroblast and the melanocyte but is mainly an important antioxidant. Vitamin C is important for the re-activation of vitamin E that has been converted into a tocopheryl radical by quenching a free radical. Vitamin E, on the other hand, seems to have virtually no metabolic action at all and is only an antioxidant in the lipid phase of the cell. Vitamin E is also denatured by light.
This daily, localised deficiency of vitamin A and the C and other skin antioxidants is insidious and pernicious. About 10 minutes of sunlight will destroy 90% of the cutaneous retinyl esters and it takes longer than 24 hours to restore normal levels[vii] Retinoid receptors on the cell membranes are destroyed at the same time and retinoid metabolic pathways become less efficient.[viii] This happens day after day and year after year and this is the main cause of photoageing. Keratinocytes produce less of the essential keratins and ceramides that ensure an effective waterproofing barrier for the skin. The horny layer becomes much thicker and rougher with a basket-weave pattern instead of being compact, thinner, but denser. UV irradiation stimulates the release of Matrix-metallo-proteinases (MMP) whereas vitamin A normally inhibits the formation of MMPs secreted by keratinocytes and fibroblasts. With a deficiency of vitamin A, MMP’s are released in greater quanitites and destroy collagen, and anchoring fibrils.[ix], [x] And the rete pegs become flattened. Of course at the same time free radicals are being generated but unfortunately the important free radical scavengers of the skin are simultaneously depleted.
Langerhans cells desperately need vitamin A and it’s deficiency prevents them from recognising DNA damage. As a result, clones of abnormal cells slowly start to develop and, years later, manifest as keratoses or skin cancer.
UV and near UV light stimulates production of melanin, but if there is adequate vitamin A this is controlled and the distribution of melanin in the skin is kept even. Vitamin A deficiency permits lentigines and melanosis.
The fibroblast produces less Glycoseaminoglycans so the skin feels drier and wrinkles show up very easily.
There is little value in looking to the diet to replenish the depleted vitamin stores in the short term because that will take too long. Cluver showed that people who suffered bad sunburn could be improved by oral supplementation of 25,000 i.u. retinyl palmitate per day[xi]. Conventional sunscreens are not able to give adequate protection from UV- A, and so vitamin A is still damaged by light, even when a person is wearing a sun protection factor of 30 or 40. Once the skin retinoids are depleted after a heavy exposure to sunlight, it takes several days before diet alone can restore the normal cutaneous retinoid levels. On the other hand, application of a vitamin A cream can restore the normal levels within hours.
Ascorbic acid is water-soluble and the cells do not build up any special stores, so the loss of vitamin C has to be replaced by the blood supply. Deficiencies of vitamin C immediately permit more free radical damage but this does not show up clinically until significant damage has been done. Defective collagen may be formed. Melanin is produced in greater quantities so pigmentation problems are more likely especially if the diet is not rich in vitamin C. It is my impression that people with high vitamin C intake have less problems with skin pigmentation. Fortunately vitamin C is easy to administer to the skin and should by preference be administered as the magnesium or sodium phosphate salt which is water-soluble, or as a palmitic ester. The most effective is ascorbyl tetra-isopalmitate.
By selecting cosmetic products which contain effective doses of vitamin A, vitamin C and other antioxidants, one can ensure that we are treating photoageing in the best way and can expect significant rejuvenation and prevention of photoageing.
[i] Wise F.,. Sulzberger, MB Yearbook of Dermatol(1938) 282
[ii] Berne, B., Nilsson, M., Vahlquist, A. UV Irradiation and Cutaneous Vitamin A: An Experimental Study in Rabbit and Human Skin. J. Invest Dermatol, (1984) 83:401-404,
[iii] Cluver S.A.Med. J.(1964) (38) 801-803
Cluver and Politzer. Sunburn and Vitamin A deficiency. S A J Sci (1965)61:306-9
[iv] Kligman AM, Current Status of Topical Tretinoin in the treatment of photoaged skin. Drugs Ageing 1992 Jan-Feb; 2(1): 7-13
[v] Antille C; Tran C; Sorg O; Carraux P; Didierjean L; Saurat JH Vitamin A exerts a photoprotective action in skin by absorbing ultraviolet B radiation. 2003, J Invest Dermatol, 121(5):1163-7
[vi] Lithgow DM, Politzer WM. Vitamin A in the treatment of
menorrhagia. S Afr Med J 1977, 51(7):191 – 193
[vii] Tran C, Sorg O, Carraux P, Didierjean L, Saurat J. Topical Delivery of Retinoids Counteracts the UVB-induced Epidermal Vitamin A Depletion in Hairless Mouse. Photochemistry and Photobiology: Vol. 73, No. 4, pp. 425–431.
[viii] Wang Z; Boudjelal M; Kang S; Voorhees JJ; Fisher GJ Ultraviolet irradiation of human skin causes functional vitamin A deficiency, preventable by all-trans retinoic acid pre-treatment
Nat Med, 1999 Apr, 5:4, 418-22
[ix] Varani J, Warner RL, Gharaee-Kermani M, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol. 2000; 114:480-486.
[x] JinHo Chung*, ZengQuan Wang*, Subhash C Datta*, Gary J Fisher* and John J Voorhees James Varani, Roscoe L Warner, Mehrnaz Gharaee-Kermani, Sem H Phan, Sewon KangVitamin A Antagonizes Decreased Cell Growth and Elevated Collagen-Degrading Matrix Metalloproteinases and Stimulates Collagen Accumulation in Naturally Aged Human Skin J ournal of Investigative Dermatology (2000) 114, 480–486; doi:10.1046/j.1523-1747
[xi] Cluver EH; Politzer WM The pathology of sun trauma. S Afr Med J, 1965 Nov, 39:41, 1051-3