While we all age, few of us want to look as old as we are. Today, Americans spend billions of dollars to counter the effects of aging. While natural aging is unavoidable, we all grow older. However, an important component of the aging process is photoaging, or the aging or appearance of aging that occurs as a result of exposure to the sun, superimposed on chronological aging. While natural aging is largely a genetic process that leads to changes at the cellular level, photoaging is a process that exacerbates the effects of natural aging, creates additional problems through cell degeneration and cellular damage, dramatically impacts the appearance of the skin and can even lead to cancers. “We are all familiar with beauty and youth, skin that’s smooth and full and tight, blemish-free, translucent in its appearance,” says Steven Mandy, M.D., Clinical Professor of Dermatology, University of Miami. “But as skin ages, the epidermis and dermis thin. There’s telangiectasia, dyspigmentation, malignant change, lipodystrophy and loss of elasticity. All of those go into creating the aged appearance, and there is no question that photoaging hastens this process significantly.” Getting Under Your Skin: A Look at Photodamage According to Barbara Gilchrest, M.D., Professor and Chair of Dermatology at Boston University School of Medicine, skin aging is a combination of two processes that change the skin from the very smooth, unblemished and highly functional skin of a young individual to the very altered and dysfunctional skin of the older adult: the clinical, histological and physiologic changes that occur naturally as the skin ages, and photoaging in which those changes are compounded by sun damage. Although skin functions may decline by more than 50% over the course of a lifetime, intrinsic aging has a relative minor impact on appearance of skin. In contrast, photoaging has a major impact on the appearance of skin. In addition, chronic exposure to the sun further compromises virtually every function, as well as being intimately related to photo carcinogenesis. “Compare the sun-protected skin of the breast of a 60-year-old woman, which is very smooth and difficult to distinguish from skin of a much younger individual, to the backs of the hands, which are hyperpigmented, coarse and studded with pre-malignant growths,” says Dr. Gilchrest. “The changes one sees with photoaging depend very much on the ability of the individual’s skin to contend with solar damage over the years with some being far better than others to being able to withstand and recover from solar insult.” Individuals who cannot handle this solar insult very well experience various mutational and dysplastic changes, including freckling, nevi and various pre-malignant and malignant changes. These people will also experience epidermal atrophy, dermal atrophy, loss of pigmentation and pseudo scars. In addition, studies show that smoking exacerbates the effects of photoaging. How does sunlight affect skin? According to Dr. Gilchrest, ultraviolet radiation causes significant changes to the cells of the skin, including DNA damage. Recent work suggests that acute DNA damage, for example UV-induced photoproducts or exidation of DNA bases, can temporarily disrupt the normal chromosome configuration and, in particular, may disrupt the telomere loop at chromosome ends, leading to DNA damage signaling through p53 tumor suppressor protein. Depending on the cell type, and severity of the damage, UV radiation will tend to push the cells to undergo apoptosis or to enter a senescent state, both recognized cancer-prevention mechanisms. Lesser damage promotes various adaptive differentiation responses, such as tanning. Interestingly, serial cell division that occurs in skin over time and that is often promoted during the hyperplastic recovery phase of UV injury, also eventually leads to telomere loop following disruption and signaling through the same DNA damage pathway involving p53. Thus, it appears that photoaging is truly a form of accelerated or premature aging in which UV-induced mutations in many genes modify the clinical picture resulting from telomere-based aging alone. In addition, many experts believe that a major complementary mechanism in aging is cumulative oxidative damage, the consequence of aerobic metabolism, which is known to damage DNA. And, it has been shown experimentally that under oxidative stress, cells senesce more rapidly. “If we look at chronic sun damage, we know that UVB irradiation introduces thymine and dimers and other cyclobutane pyrimidine dimmers, that then can produce mutations in coding sequences in the DNA giving rise, for example, to signature mutations in the p53.” says Dr. Gilchrest. “When mutations occur in a sufficient number of key regulatory genes before the senescence or apoptosis response is triggered, cancer results.” UVA photons are also implicated in DNA mutations that lead to cancer, and UVA is also implicated in photoaging and believed to act primarily indirectly through oxidative damage. As noted above, oxidized DNA residues can also push signaling through the telomere damage recognition mechanism. “With this in mind, I would suggest that therapy, at least medical therapy, of aging and photoaging must logically reduce DNA damage through sunscreen use and protection against oxidative damage via anti-oxidant approaches,” says Dr. Gilchrest. “I think in the coming decade we will also see approaches that employ enhancement of these innate DNA protective mechanisms within cells.” Photoaging’s Effect on Collagen In addition to the genetic damage, John Voorhees, M.D., Professor and Chairman of Dermatology at the University of Michigan, has conducted studies that demonstrated the damaging effect that sun exposure can have on the fundamental building block of skin — collagen. “The vast majority of the protein in the dermis is type 1 collagen, which imparts the form, the function and the strength of the skin,” says Dr. Voorhees. “Chronic exposure to the sun results in a temporary decrease in the collagen content of the skin. When this exposure occurs on a repetitive basis over many years, the skin cannot recover and the collagen levels do not return to normal.” UV light generates hydroxyl radicals. This hydroxyl radical, in addition to damaging DNA, activates the tyrosine kinase of the epidermal growth factor receptor and activates three modules: ERK, JNK and P38. JNK is very important in natural aging, while ERK is important in photoaging. “In both cases we have the activation of activator protein 1, which activates collagenase, which will degrade the dermis of human skin when exposed to the sun,” says Dr. Voorhees. “In addition, UV activates collagenase and gelatinase, which breaks down the collagen that you already had.” UV blocks the TGF beta-receptor No. 2 by turning off the gene that codes for this receptor, and that, in turn, causes it to be non-functional. If it’s not there, it cannot activate the pro-collagen promoter, resulting in a reduction in collagen formation. So, both increased destruction and reduced formation of collagen are collaborating to cause photoaging. Chronic UV injury creates fragmented and disorganized collagen in the dermis, leading to altered signal transduction compromising the ability of the fibroblast to perceive its situation with respect to the extracellular matrix — the collagen and the other macromolecules in the dermis of human skin. In studies, fibroblasts removed from sun-exposed areas could be induced to make collagen to the same level as fibroblasts removed from sun-protected skin. This means that the collagen manufacturing mechanism in sun-exposed skin remains intact, but for some reason will not produce collagen. “We know that a fibroblast that’s tense, and in that situation it manufactures collagen, has little or no collagenase,” says Dr. Voorhees. “But when a fibroblast is relaxed, it makes very little collagen and makes a lot of collagenase, which is what we find in chronically photoaged skin.” Treatment of Photoaged Skin One of the best approaches to fighting photoaging is prevention, and with prevention, you’re talking about avoiding UV exposure as much as possible, and if you’re going to be in the sun, it’s important to effectively use sunscreens, protective clothing and hats. Other approaches to prevent photoaging include the use of retinoic acid or some other retinoid, which can reduce the level of collagen breakdown in the skin. Antioxidants also can play a role by reducing the amount of oxides that can be turned into damaging hydroxyl radical, which can damage DNA and protein molecules. “We have tried a variety of antioxidants. One of these is Mucomyst, a drug that forms glutathione, a water-soluble antioxidant, when applied to the skin,” says Dr. Voorhees. “These antioxidants have not been approved for use in humans, and none have been studied in a way that would allow one to make any conclusions about efficacy in man.” Traditional treatment of photoaged skin involves procedures, such as topical abrasions, laser and intense pulsed light treatments, as well as the application of vitamin therapies, all of which can help restore a more youthful appearance to skin. Mitchel P. Goldman, M.D., Medical Director of La Jolla Spa MD and Associate Clinical Professor of Dermatology at the University of California, San Diego, uses phototherapies to rejuvenate photodamaged skin. Among the tools that he uses are the intense pulsed light laser by Lumenis, the Cool Touch laser and the V-Star pulsed dye laser. “To truly repair photodamaged skin, in addition to rejuvenating the skin surface, you need to go below the surface and remodel the dermis,” says Dr. Goldman. “We use our devices to stimulate new collagen formation. The laser stimulates fibroblasts to enhance collagen production producing a more well organized matrix.” The Cool Touch laser is an infrared laser that acts by going right through the epidermis. With this laser, a cryogen pulse cools the skin to 0 degrees and then the laser pulse passes through the skin and heats the skin to a sub-damaging level of 45 degrees centigrade, and the skin temperature comes back to normal. The heat goes down into the superficial papillary dermis. This then stimulates fibroblasts. On the other hand, the intense pulsed light is used primarily to correct problems with pigmentation and telangiectasia. “Most laser surgeons will actually combine these two different devices to correct the different problems of photodamage,” says Dr. Goldman. Recently, Dr. Goldman has been having success combining laser therapies with topical chemicals, similar to the ALA PDT therapy. “Our approach is not the traditional approach, which most patients would not tolerate because of the time involved,” says Dr. Goldman. “What we do is put the ALA on for 1 hour, and then we treat our patients with the intense pulsed light.” Dr. Goldman sees histological evidence of new collagen formation in his patients, including a thickening of the dermis with new collagen and a re-polarization or normalization of the ridge pattern and the epidermis after biopsies. His treatments result in an increase in the number of elastic fibers and a normalization of the epidermis. “We found that there was an absolute improvement in the skin texture and elimination of telangiectasias and pigmentation in virtually all of our patients,” says Dr. Goldman. “The skin does have a smoother appearance even though it’s very difficult to measure quantitatively, there appears to be a decrease in pore size, and there’s a decrease in the lentigines, along with the telangiectasias. You can see improvement after one, two or three treatments. This improvement with combined ALA IPL treatment produces results equivalent to three to four IPL treatments alone.” Dr. Goldman warns that patients should be made aware of possible side effects, including hypopigmentation, temporary and mild crusting and erythematous and rectangular footprinting. Most side effects, which occur in fewer than 5% of patients, take 1 to 2 weeks to resolve, depending on the patient’s skin. So how effective can these treatments really be? “We are approaching ways that we can measure improvement so that we can actually match the sun damaged skin to the non-sun damaged skin,” says Dr. Goldman. “Using the Primos System, we analyze 3D images, and with the Canfield Visia system we measure ultraviolet and visable light imperfections on the skin. These systems allow us to see definite improvement, measurable at 1 month and then at 2 months. We also can look at the roughness, as well as fine lines and coarse lines, and also try to see some kind of improvement measuring it with these systems.” Vitamins and Photodamaged Skin Sometimes repairing photodamage is just the beginning of the process to restore photoaged skin. To truly rejuvenate, a physician has to look at not only the skin but also the fat, the muscle and the hard structures beneath when attempting to rejuvenate a patient. “We saw patients who would go through major resurfacing, either de-chemical peeling, dermabrasion or carbon dioxide laser resurfacing, and while they looked better, they certainly didn’t look that much better,” says Richard Glogau, M.D., Clinical Professor at the University of California in San Francisco. “The reason is because only one aspect of the problem has been addressed. The laser basically takes care of the skin texture and quality, but it doesn’t do anything for the volume of the compartments underneath the skin or the musculature.” Physicians often need to treat not only the photodamage but also the affect on underlying tissues. As the face ages and it loses the roundness and the fullness of contour that comes from normal amounts of subcutaneous fat, everything flattens out in the face, and patients lose volume and the nice round contours. “Even if only treating photodamage, we’re back into the four Rs, relax, refill, re-drape and resurface,” says Dr. Glogau. Another approach to repairing damage caused by chronic sun exposure involves the use of vitamins. According to Leslie Baumann, M.D., Professor and Director of the University of Miami Cosmetic Center, vitamin E can protect membrane lipids from peroxidation, which can reduce free radicals after UV exposure. Dr. Baumann cautions, however, that there is no evidence at all of the affect of vitamin E on wrinkles. “In a double-blind, placebo-controlled trial, we found that in 90% of the patients, the scar treated with vitamin E was either no different or worse,” says Dr. Baumann. “However, 33% of the patients developed a severe contact dermatitis.” Niacinamide (nicotinamide), which is one of the B vitamins, is a precursor to niacin and cannot be made by the skin cells. It functions as a central component in coenzyme 1 and coenzyme 2. These coenzymes either donate or accept hydrogen ions in vital oxidation reduction reactions. Because of that, there are many effects with niacinamide. “Niacinamide is necessary to repair DNA caused by UVA exposure,” says Dr. Baumann. “Studies show that cells depleted of niacin have been shown to have genomic instability. So I think there’s convincing data that niacin and niacinamide are important for DNA repair.” Dr. Baumann also states that studies show that topical nicotinamide applied to mouse skin resulted in a 70% decrease in UV-induced skin cancers and nearly complete prevention of photo immune suppression, but there is no information on its ability to penetrate human skin. A study showed that nicotinamide increases the biosynthesis of ceramides and other stratum corneum lipids, which is important in the permeability barrier. Another study shows that niacinamide can reduce the cutaneous pigmentation and suppression of melanasome transfer. Conclusion There are a variety of rejuvenation strategies to restore youthful appearances to older skin from topicals, such as retinoids, to injectables, such as Botox and collagen. There are non-ablative technologies, new light technologies and resurfacing of various types from acid peels, dermabrasions and lasers. All of these approaches can be used to restore a youthful, more healthy look to photodamaged skin. “We rejuvenate because there’s a social bias and a dismissiveness toward an aged appearance,” says Dr. Mandy. “Beauty does imply health and vitality, significance and relevance. So beauty matters. It promotes pleasure, it rivets attention, it impels action, and it insures the survival of our genes.”
Current Therapies for Treating Photodamaged Skin
While we all age, few of us want to look as old as we are. Today, Americans spend billions of dollars to counter the effects of aging. While natural aging is unavoidable, we all grow older. However, an important component of the aging process is photoaging, or the aging or appearance of aging that occurs as a result of exposure to the sun, superimposed on chronological aging. While natural aging is largely a genetic process that leads to changes at the cellular level, photoaging is a process that exacerbates the effects of natural aging, creates additional problems through cell degeneration and cellular damage, dramatically impacts the appearance of the skin and can even lead to cancers. “We are all familiar with beauty and youth, skin that’s smooth and full and tight, blemish-free, translucent in its appearance,” says Steven Mandy, M.D., Clinical Professor of Dermatology, University of Miami. “But as skin ages, the epidermis and dermis thin. There’s telangiectasia, dyspigmentation, malignant change, lipodystrophy and loss of elasticity. All of those go into creating the aged appearance, and there is no question that photoaging hastens this process significantly.” Getting Under Your Skin: A Look at Photodamage According to Barbara Gilchrest, M.D., Professor and Chair of Dermatology at Boston University School of Medicine, skin aging is a combination of two processes that change the skin from the very smooth, unblemished and highly functional skin of a young individual to the very altered and dysfunctional skin of the older adult: the clinical, histological and physiologic changes that occur naturally as the skin ages, and photoaging in which those changes are compounded by sun damage. Although skin functions may decline by more than 50% over the course of a lifetime, intrinsic aging has a relative minor impact on appearance of skin. In contrast, photoaging has a major impact on the appearance of skin. In addition, chronic exposure to the sun further compromises virtually every function, as well as being intimately related to photo carcinogenesis. “Compare the sun-protected skin of the breast of a 60-year-old woman, which is very smooth and difficult to distinguish from skin of a much younger individual, to the backs of the hands, which are hyperpigmented, coarse and studded with pre-malignant growths,” says Dr. Gilchrest. “The changes one sees with photoaging depend very much on the ability of the individual’s skin to contend with solar damage over the years with some being far better than others to being able to withstand and recover from solar insult.” Individuals who cannot handle this solar insult very well experience various mutational and dysplastic changes, including freckling, nevi and various pre-malignant and malignant changes. These people will also experience epidermal atrophy, dermal atrophy, loss of pigmentation and pseudo scars. In addition, studies show that smoking exacerbates the effects of photoaging. How does sunlight affect skin? According to Dr. Gilchrest, ultraviolet radiation causes significant changes to the cells of the skin, including DNA damage. Recent work suggests that acute DNA damage, for example UV-induced photoproducts or exidation of DNA bases, can temporarily disrupt the normal chromosome configuration and, in particular, may disrupt the telomere loop at chromosome ends, leading to DNA damage signaling through p53 tumor suppressor protein. Depending on the cell type, and severity of the damage, UV radiation will tend to push the cells to undergo apoptosis or to enter a senescent state, both recognized cancer-prevention mechanisms. Lesser damage promotes various adaptive differentiation responses, such as tanning. Interestingly, serial cell division that occurs in skin over time and that is often promoted during the hyperplastic recovery phase of UV injury, also eventually leads to telomere loop following disruption and signaling through the same DNA damage pathway involving p53. Thus, it appears that photoaging is truly a form of accelerated or premature aging in which UV-induced mutations in many genes modify the clinical picture resulting from telomere-based aging alone. In addition, many experts believe that a major complementary mechanism in aging is cumulative oxidative damage, the consequence of aerobic metabolism, which is known to damage DNA. And, it has been shown experimentally that under oxidative stress, cells senesce more rapidly. “If we look at chronic sun damage, we know that UVB irradiation introduces thymine and dimers and other cyclobutane pyrimidine dimmers, that then can produce mutations in coding sequences in the DNA giving rise, for example, to signature mutations in the p53.” says Dr. Gilchrest. “When mutations occur in a sufficient number of key regulatory genes before the senescence or apoptosis response is triggered, cancer results.” UVA photons are also implicated in DNA mutations that lead to cancer, and UVA is also implicated in photoaging and believed to act primarily indirectly through oxidative damage. As noted above, oxidized DNA residues can also push signaling through the telomere damage recognition mechanism. “With this in mind, I would suggest that therapy, at least medical therapy, of aging and photoaging must logically reduce DNA damage through sunscreen use and protection against oxidative damage via anti-oxidant approaches,” says Dr. Gilchrest. “I think in the coming decade we will also see approaches that employ enhancement of these innate DNA protective mechanisms within cells.” Photoaging’s Effect on Collagen In addition to the genetic damage, John Voorhees, M.D., Professor and Chairman of Dermatology at the University of Michigan, has conducted studies that demonstrated the damaging effect that sun exposure can have on the fundamental building block of skin — collagen. “The vast majority of the protein in the dermis is type 1 collagen, which imparts the form, the function and the strength of the skin,” says Dr. Voorhees. “Chronic exposure to the sun results in a temporary decrease in the collagen content of the skin. When this exposure occurs on a repetitive basis over many years, the skin cannot recover and the collagen levels do not return to normal.” UV light generates hydroxyl radicals. This hydroxyl radical, in addition to damaging DNA, activates the tyrosine kinase of the epidermal growth factor receptor and activates three modules: ERK, JNK and P38. JNK is very important in natural aging, while ERK is important in photoaging. “In both cases we have the activation of activator protein 1, which activates collagenase, which will degrade the dermis of human skin when exposed to the sun,” says Dr. Voorhees. “In addition, UV activates collagenase and gelatinase, which breaks down the collagen that you already had.” UV blocks the TGF beta-receptor No. 2 by turning off the gene that codes for this receptor, and that, in turn, causes it to be non-functional. If it’s not there, it cannot activate the pro-collagen promoter, resulting in a reduction in collagen formation. So, both increased destruction and reduced formation of collagen are collaborating to cause photoaging. Chronic UV injury creates fragmented and disorganized collagen in the dermis, leading to altered signal transduction compromising the ability of the fibroblast to perceive its situation with respect to the extracellular matrix — the collagen and the other macromolecules in the dermis of human skin. In studies, fibroblasts removed from sun-exposed areas could be induced to make collagen to the same level as fibroblasts removed from sun-protected skin. This means that the collagen manufacturing mechanism in sun-exposed skin remains intact, but for some reason will not produce collagen. “We know that a fibroblast that’s tense, and in that situation it manufactures collagen, has little or no collagenase,” says Dr. Voorhees. “But when a fibroblast is relaxed, it makes very little collagen and makes a lot of collagenase, which is what we find in chronically photoaged skin.” Treatment of Photoaged Skin One of the best approaches to fighting photoaging is prevention, and with prevention, you’re talking about avoiding UV exposure as much as possible, and if you’re going to be in the sun, it’s important to effectively use sunscreens, protective clothing and hats. Other approaches to prevent photoaging include the use of retinoic acid or some other retinoid, which can reduce the level of collagen breakdown in the skin. Antioxidants also can play a role by reducing the amount of oxides that can be turned into damaging hydroxyl radical, which can damage DNA and protein molecules. “We have tried a variety of antioxidants. One of these is Mucomyst, a drug that forms glutathione, a water-soluble antioxidant, when applied to the skin,” says Dr. Voorhees. “These antioxidants have not been approved for use in humans, and none have been studied in a way that would allow one to make any conclusions about efficacy in man.” Traditional treatment of photoaged skin involves procedures, such as topical abrasions, laser and intense pulsed light treatments, as well as the application of vitamin therapies, all of which can help restore a more youthful appearance to skin. Mitchel P. Goldman, M.D., Medical Director of La Jolla Spa MD and Associate Clinical Professor of Dermatology at the University of California, San Diego, uses phototherapies to rejuvenate photodamaged skin. Among the tools that he uses are the intense pulsed light laser by Lumenis, the Cool Touch laser and the V-Star pulsed dye laser. “To truly repair photodamaged skin, in addition to rejuvenating the skin surface, you need to go below the surface and remodel the dermis,” says Dr. Goldman. “We use our devices to stimulate new collagen formation. The laser stimulates fibroblasts to enhance collagen production producing a more well organized matrix.” The Cool Touch laser is an infrared laser that acts by going right through the epidermis. With this laser, a cryogen pulse cools the skin to 0 degrees and then the laser pulse passes through the skin and heats the skin to a sub-damaging level of 45 degrees centigrade, and the skin temperature comes back to normal. The heat goes down into the superficial papillary dermis. This then stimulates fibroblasts. On the other hand, the intense pulsed light is used primarily to correct problems with pigmentation and telangiectasia. “Most laser surgeons will actually combine these two different devices to correct the different problems of photodamage,” says Dr. Goldman. Recently, Dr. Goldman has been having success combining laser therapies with topical chemicals, similar to the ALA PDT therapy. “Our approach is not the traditional approach, which most patients would not tolerate because of the time involved,” says Dr. Goldman. “What we do is put the ALA on for 1 hour, and then we treat our patients with the intense pulsed light.” Dr. Goldman sees histological evidence of new collagen formation in his patients, including a thickening of the dermis with new collagen and a re-polarization or normalization of the ridge pattern and the epidermis after biopsies. His treatments result in an increase in the number of elastic fibers and a normalization of the epidermis. “We found that there was an absolute improvement in the skin texture and elimination of telangiectasias and pigmentation in virtually all of our patients,” says Dr. Goldman. “The skin does have a smoother appearance even though it’s very difficult to measure quantitatively, there appears to be a decrease in pore size, and there’s a decrease in the lentigines, along with the telangiectasias. You can see improvement after one, two or three treatments. This improvement with combined ALA IPL treatment produces results equivalent to three to four IPL treatments alone.” Dr. Goldman warns that patients should be made aware of possible side effects, including hypopigmentation, temporary and mild crusting and erythematous and rectangular footprinting. Most side effects, which occur in fewer than 5% of patients, take 1 to 2 weeks to resolve, depending on the patient’s skin. So how effective can these treatments really be? “We are approaching ways that we can measure improvement so that we can actually match the sun damaged skin to the non-sun damaged skin,” says Dr. Goldman. “Using the Primos System, we analyze 3D images, and with the Canfield Visia system we measure ultraviolet and visable light imperfections on the skin. These systems allow us to see definite improvement, measurable at 1 month and then at 2 months. We also can look at the roughness, as well as fine lines and coarse lines, and also try to see some kind of improvement measuring it with these systems.” Vitamins and Photodamaged Skin Sometimes repairing photodamage is just the beginning of the process to restore photoaged skin. To truly rejuvenate, a physician has to look at not only the skin but also the fat, the muscle and the hard structures beneath when attempting to rejuvenate a patient. “We saw patients who would go through major resurfacing, either de-chemical peeling, dermabrasion or carbon dioxide laser resurfacing, and while they looked better, they certainly didn’t look that much better,” says Richard Glogau, M.D., Clinical Professor at the University of California in San Francisco. “The reason is because only one aspect of the problem has been addressed. The laser basically takes care of the skin texture and quality, but it doesn’t do anything for the volume of the compartments underneath the skin or the musculature.” Physicians often need to treat not only the photodamage but also the affect on underlying tissues. As the face ages and it loses the roundness and the fullness of contour that comes from normal amounts of subcutaneous fat, everything flattens out in the face, and patients lose volume and the nice round contours. “Even if only treating photodamage, we’re back into the four Rs, relax, refill, re-drape and resurface,” says Dr. Glogau. Another approach to repairing damage caused by chronic sun exposure involves the use of vitamins. According to Leslie Baumann, M.D., Professor and Director of the University of Miami Cosmetic Center, vitamin E can protect membrane lipids from peroxidation, which can reduce free radicals after UV exposure. Dr. Baumann cautions, however, that there is no evidence at all of the affect of vitamin E on wrinkles. “In a double-blind, placebo-controlled trial, we found that in 90% of the patients, the scar treated with vitamin E was either no different or worse,” says Dr. Baumann. “However, 33% of the patients developed a severe contact dermatitis.” Niacinamide (nicotinamide), which is one of the B vitamins, is a precursor to niacin and cannot be made by the skin cells. It functions as a central component in coenzyme 1 and coenzyme 2. These coenzymes either donate or accept hydrogen ions in vital oxidation reduction reactions. Because of that, there are many effects with niacinamide. “Niacinamide is necessary to repair DNA caused by UVA exposure,” says Dr. Baumann. “Studies show that cells depleted of niacin have been shown to have genomic instability. So I think there’s convincing data that niacin and niacinamide are important for DNA repair.” Dr. Baumann also states that studies show that topical nicotinamide applied to mouse skin resulted in a 70% decrease in UV-induced skin cancers and nearly complete prevention of photo immune suppression, but there is no information on its ability to penetrate human skin. A study showed that nicotinamide increases the biosynthesis of ceramides and other stratum corneum lipids, which is important in the permeability barrier. Another study shows that niacinamide can reduce the cutaneous pigmentation and suppression of melanasome transfer. Conclusion There are a variety of rejuvenation strategies to restore youthful appearances to older skin from topicals, such as retinoids, to injectables, such as Botox and collagen. There are non-ablative technologies, new light technologies and resurfacing of various types from acid peels, dermabrasions and lasers. All of these approaches can be used to restore a youthful, more healthy look to photodamaged skin. “We rejuvenate because there’s a social bias and a dismissiveness toward an aged appearance,” says Dr. Mandy. “Beauty does imply health and vitality, significance and relevance. So beauty matters. It promotes pleasure, it rivets attention, it impels action, and it insures the survival of our genes.”
While we all age, few of us want to look as old as we are. Today, Americans spend billions of dollars to counter the effects of aging. While natural aging is unavoidable, we all grow older. However, an important component of the aging process is photoaging, or the aging or appearance of aging that occurs as a result of exposure to the sun, superimposed on chronological aging. While natural aging is largely a genetic process that leads to changes at the cellular level, photoaging is a process that exacerbates the effects of natural aging, creates additional problems through cell degeneration and cellular damage, dramatically impacts the appearance of the skin and can even lead to cancers. “We are all familiar with beauty and youth, skin that’s smooth and full and tight, blemish-free, translucent in its appearance,” says Steven Mandy, M.D., Clinical Professor of Dermatology, University of Miami. “But as skin ages, the epidermis and dermis thin. There’s telangiectasia, dyspigmentation, malignant change, lipodystrophy and loss of elasticity. All of those go into creating the aged appearance, and there is no question that photoaging hastens this process significantly.” Getting Under Your Skin: A Look at Photodamage According to Barbara Gilchrest, M.D., Professor and Chair of Dermatology at Boston University School of Medicine, skin aging is a combination of two processes that change the skin from the very smooth, unblemished and highly functional skin of a young individual to the very altered and dysfunctional skin of the older adult: the clinical, histological and physiologic changes that occur naturally as the skin ages, and photoaging in which those changes are compounded by sun damage. Although skin functions may decline by more than 50% over the course of a lifetime, intrinsic aging has a relative minor impact on appearance of skin. In contrast, photoaging has a major impact on the appearance of skin. In addition, chronic exposure to the sun further compromises virtually every function, as well as being intimately related to photo carcinogenesis. “Compare the sun-protected skin of the breast of a 60-year-old woman, which is very smooth and difficult to distinguish from skin of a much younger individual, to the backs of the hands, which are hyperpigmented, coarse and studded with pre-malignant growths,” says Dr. Gilchrest. “The changes one sees with photoaging depend very much on the ability of the individual’s skin to contend with solar damage over the years with some being far better than others to being able to withstand and recover from solar insult.” Individuals who cannot handle this solar insult very well experience various mutational and dysplastic changes, including freckling, nevi and various pre-malignant and malignant changes. These people will also experience epidermal atrophy, dermal atrophy, loss of pigmentation and pseudo scars. In addition, studies show that smoking exacerbates the effects of photoaging. How does sunlight affect skin? According to Dr. Gilchrest, ultraviolet radiation causes significant changes to the cells of the skin, including DNA damage. Recent work suggests that acute DNA damage, for example UV-induced photoproducts or exidation of DNA bases, can temporarily disrupt the normal chromosome configuration and, in particular, may disrupt the telomere loop at chromosome ends, leading to DNA damage signaling through p53 tumor suppressor protein. Depending on the cell type, and severity of the damage, UV radiation will tend to push the cells to undergo apoptosis or to enter a senescent state, both recognized cancer-prevention mechanisms. Lesser damage promotes various adaptive differentiation responses, such as tanning. Interestingly, serial cell division that occurs in skin over time and that is often promoted during the hyperplastic recovery phase of UV injury, also eventually leads to telomere loop following disruption and signaling through the same DNA damage pathway involving p53. Thus, it appears that photoaging is truly a form of accelerated or premature aging in which UV-induced mutations in many genes modify the clinical picture resulting from telomere-based aging alone. In addition, many experts believe that a major complementary mechanism in aging is cumulative oxidative damage, the consequence of aerobic metabolism, which is known to damage DNA. And, it has been shown experimentally that under oxidative stress, cells senesce more rapidly. “If we look at chronic sun damage, we know that UVB irradiation introduces thymine and dimers and other cyclobutane pyrimidine dimmers, that then can produce mutations in coding sequences in the DNA giving rise, for example, to signature mutations in the p53.” says Dr. Gilchrest. “When mutations occur in a sufficient number of key regulatory genes before the senescence or apoptosis response is triggered, cancer results.” UVA photons are also implicated in DNA mutations that lead to cancer, and UVA is also implicated in photoaging and believed to act primarily indirectly through oxidative damage. As noted above, oxidized DNA residues can also push signaling through the telomere damage recognition mechanism. “With this in mind, I would suggest that therapy, at least medical therapy, of aging and photoaging must logically reduce DNA damage through sunscreen use and protection against oxidative damage via anti-oxidant approaches,” says Dr. Gilchrest. “I think in the coming decade we will also see approaches that employ enhancement of these innate DNA protective mechanisms within cells.” Photoaging’s Effect on Collagen In addition to the genetic damage, John Voorhees, M.D., Professor and Chairman of Dermatology at the University of Michigan, has conducted studies that demonstrated the damaging effect that sun exposure can have on the fundamental building block of skin — collagen. “The vast majority of the protein in the dermis is type 1 collagen, which imparts the form, the function and the strength of the skin,” says Dr. Voorhees. “Chronic exposure to the sun results in a temporary decrease in the collagen content of the skin. When this exposure occurs on a repetitive basis over many years, the skin cannot recover and the collagen levels do not return to normal.” UV light generates hydroxyl radicals. This hydroxyl radical, in addition to damaging DNA, activates the tyrosine kinase of the epidermal growth factor receptor and activates three modules: ERK, JNK and P38. JNK is very important in natural aging, while ERK is important in photoaging. “In both cases we have the activation of activator protein 1, which activates collagenase, which will degrade the dermis of human skin when exposed to the sun,” says Dr. Voorhees. “In addition, UV activates collagenase and gelatinase, which breaks down the collagen that you already had.” UV blocks the TGF beta-receptor No. 2 by turning off the gene that codes for this receptor, and that, in turn, causes it to be non-functional. If it’s not there, it cannot activate the pro-collagen promoter, resulting in a reduction in collagen formation. So, both increased destruction and reduced formation of collagen are collaborating to cause photoaging. Chronic UV injury creates fragmented and disorganized collagen in the dermis, leading to altered signal transduction compromising the ability of the fibroblast to perceive its situation with respect to the extracellular matrix — the collagen and the other macromolecules in the dermis of human skin. In studies, fibroblasts removed from sun-exposed areas could be induced to make collagen to the same level as fibroblasts removed from sun-protected skin. This means that the collagen manufacturing mechanism in sun-exposed skin remains intact, but for some reason will not produce collagen. “We know that a fibroblast that’s tense, and in that situation it manufactures collagen, has little or no collagenase,” says Dr. Voorhees. “But when a fibroblast is relaxed, it makes very little collagen and makes a lot of collagenase, which is what we find in chronically photoaged skin.” Treatment of Photoaged Skin One of the best approaches to fighting photoaging is prevention, and with prevention, you’re talking about avoiding UV exposure as much as possible, and if you’re going to be in the sun, it’s important to effectively use sunscreens, protective clothing and hats. Other approaches to prevent photoaging include the use of retinoic acid or some other retinoid, which can reduce the level of collagen breakdown in the skin. Antioxidants also can play a role by reducing the amount of oxides that can be turned into damaging hydroxyl radical, which can damage DNA and protein molecules. “We have tried a variety of antioxidants. One of these is Mucomyst, a drug that forms glutathione, a water-soluble antioxidant, when applied to the skin,” says Dr. Voorhees. “These antioxidants have not been approved for use in humans, and none have been studied in a way that would allow one to make any conclusions about efficacy in man.” Traditional treatment of photoaged skin involves procedures, such as topical abrasions, laser and intense pulsed light treatments, as well as the application of vitamin therapies, all of which can help restore a more youthful appearance to skin. Mitchel P. Goldman, M.D., Medical Director of La Jolla Spa MD and Associate Clinical Professor of Dermatology at the University of California, San Diego, uses phototherapies to rejuvenate photodamaged skin. Among the tools that he uses are the intense pulsed light laser by Lumenis, the Cool Touch laser and the V-Star pulsed dye laser. “To truly repair photodamaged skin, in addition to rejuvenating the skin surface, you need to go below the surface and remodel the dermis,” says Dr. Goldman. “We use our devices to stimulate new collagen formation. The laser stimulates fibroblasts to enhance collagen production producing a more well organized matrix.” The Cool Touch laser is an infrared laser that acts by going right through the epidermis. With this laser, a cryogen pulse cools the skin to 0 degrees and then the laser pulse passes through the skin and heats the skin to a sub-damaging level of 45 degrees centigrade, and the skin temperature comes back to normal. The heat goes down into the superficial papillary dermis. This then stimulates fibroblasts. On the other hand, the intense pulsed light is used primarily to correct problems with pigmentation and telangiectasia. “Most laser surgeons will actually combine these two different devices to correct the different problems of photodamage,” says Dr. Goldman. Recently, Dr. Goldman has been having success combining laser therapies with topical chemicals, similar to the ALA PDT therapy. “Our approach is not the traditional approach, which most patients would not tolerate because of the time involved,” says Dr. Goldman. “What we do is put the ALA on for 1 hour, and then we treat our patients with the intense pulsed light.” Dr. Goldman sees histological evidence of new collagen formation in his patients, including a thickening of the dermis with new collagen and a re-polarization or normalization of the ridge pattern and the epidermis after biopsies. His treatments result in an increase in the number of elastic fibers and a normalization of the epidermis. “We found that there was an absolute improvement in the skin texture and elimination of telangiectasias and pigmentation in virtually all of our patients,” says Dr. Goldman. “The skin does have a smoother appearance even though it’s very difficult to measure quantitatively, there appears to be a decrease in pore size, and there’s a decrease in the lentigines, along with the telangiectasias. You can see improvement after one, two or three treatments. This improvement with combined ALA IPL treatment produces results equivalent to three to four IPL treatments alone.” Dr. Goldman warns that patients should be made aware of possible side effects, including hypopigmentation, temporary and mild crusting and erythematous and rectangular footprinting. Most side effects, which occur in fewer than 5% of patients, take 1 to 2 weeks to resolve, depending on the patient’s skin. So how effective can these treatments really be? “We are approaching ways that we can measure improvement so that we can actually match the sun damaged skin to the non-sun damaged skin,” says Dr. Goldman. “Using the Primos System, we analyze 3D images, and with the Canfield Visia system we measure ultraviolet and visable light imperfections on the skin. These systems allow us to see definite improvement, measurable at 1 month and then at 2 months. We also can look at the roughness, as well as fine lines and coarse lines, and also try to see some kind of improvement measuring it with these systems.” Vitamins and Photodamaged Skin Sometimes repairing photodamage is just the beginning of the process to restore photoaged skin. To truly rejuvenate, a physician has to look at not only the skin but also the fat, the muscle and the hard structures beneath when attempting to rejuvenate a patient. “We saw patients who would go through major resurfacing, either de-chemical peeling, dermabrasion or carbon dioxide laser resurfacing, and while they looked better, they certainly didn’t look that much better,” says Richard Glogau, M.D., Clinical Professor at the University of California in San Francisco. “The reason is because only one aspect of the problem has been addressed. The laser basically takes care of the skin texture and quality, but it doesn’t do anything for the volume of the compartments underneath the skin or the musculature.” Physicians often need to treat not only the photodamage but also the affect on underlying tissues. As the face ages and it loses the roundness and the fullness of contour that comes from normal amounts of subcutaneous fat, everything flattens out in the face, and patients lose volume and the nice round contours. “Even if only treating photodamage, we’re back into the four Rs, relax, refill, re-drape and resurface,” says Dr. Glogau. Another approach to repairing damage caused by chronic sun exposure involves the use of vitamins. According to Leslie Baumann, M.D., Professor and Director of the University of Miami Cosmetic Center, vitamin E can protect membrane lipids from peroxidation, which can reduce free radicals after UV exposure. Dr. Baumann cautions, however, that there is no evidence at all of the affect of vitamin E on wrinkles. “In a double-blind, placebo-controlled trial, we found that in 90% of the patients, the scar treated with vitamin E was either no different or worse,” says Dr. Baumann. “However, 33% of the patients developed a severe contact dermatitis.” Niacinamide (nicotinamide), which is one of the B vitamins, is a precursor to niacin and cannot be made by the skin cells. It functions as a central component in coenzyme 1 and coenzyme 2. These coenzymes either donate or accept hydrogen ions in vital oxidation reduction reactions. Because of that, there are many effects with niacinamide. “Niacinamide is necessary to repair DNA caused by UVA exposure,” says Dr. Baumann. “Studies show that cells depleted of niacin have been shown to have genomic instability. So I think there’s convincing data that niacin and niacinamide are important for DNA repair.” Dr. Baumann also states that studies show that topical nicotinamide applied to mouse skin resulted in a 70% decrease in UV-induced skin cancers and nearly complete prevention of photo immune suppression, but there is no information on its ability to penetrate human skin. A study showed that nicotinamide increases the biosynthesis of ceramides and other stratum corneum lipids, which is important in the permeability barrier. Another study shows that niacinamide can reduce the cutaneous pigmentation and suppression of melanasome transfer. Conclusion There are a variety of rejuvenation strategies to restore youthful appearances to older skin from topicals, such as retinoids, to injectables, such as Botox and collagen. There are non-ablative technologies, new light technologies and resurfacing of various types from acid peels, dermabrasions and lasers. All of these approaches can be used to restore a youthful, more healthy look to photodamaged skin. “We rejuvenate because there’s a social bias and a dismissiveness toward an aged appearance,” says Dr. Mandy. “Beauty does imply health and vitality, significance and relevance. So beauty matters. It promotes pleasure, it rivets attention, it impels action, and it insures the survival of our genes.”
