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Life Extension Magazine

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January 2003

Combating Skin Aging


The concept of controlling human aging remains controversial. No one disagrees, however, that individuals can significantly influence the rate at which their skin ages.

For instance, if a person wants to accelerate skin degradation, all they have to do is expose themselves to lots of ultraviolet radiation, cigarette smoke, and ethanol. Even second-hand cigarette smoke prematurely ages the skin.

Factors that induce skin damage involve the excessive production of free radicals. Protecting against these free radical insults is a proven way to slow the effects of aging.

Recently published papers confirm that a decline in natural antioxidant systems is a key factor responsible for the unsightly appearance of aged skin.

The ultimate question becomes: Can the application of topical antioxidants to the skin's surface induce a noticeable anti-aging effect? This article reveals novel findings made by research scientists working on the front lines in the battle to prevent and reverse skin aging.

The skin, as the outermost barrier of the body, is exposed to various sources of oxidative stress, in particular UV-irradiation and environmental toxins such as cigarette smoke, air pollution, etc. Internally, the skin is attacked like any other organ, through processes involving glycation (protein cross-linking), collagen-elastin degradation and free radical-induced injury.

One way of mitigating this process is to increase levels of protective antioxidants through a diet rich in fruits and vegetables or by direct topical application. Indeed, various animal and human studies have proved that topically applied antioxidants, especially vitamins C and E, as well as alpha lipoic acid exert protective effects against free radical damage (oxidative stress).1

Free radicals form in skin upon ultraviolet exposure. Acute and chronic photo radiation damage depletes the body's natural antioxidant enzyme systems and increases oxidative protein modifications (cross-links). These pathological effects are found in the upper and lower layers of the skin. Cross-linked (glycated) proteins are classic characteristics of skin aging. Cross-linked proteins in the skin result in stiffening, wrinkling and the unsightly leathery appearance.2

New studies confirm efficacy of topical antioxidants

In a double-blind study, a topical vitamin C complex was applied to one-half of the face and a placebo gel to the opposite side. Clinical evaluation of wrinkling, pigmentation, inflammation and hydration was performed prior to the study and at weeks 4, 8 and 12. The results showed a statistically significant improvement of the vitamin C-treated side, with decreased photoaging scores of the cheeks and the peri-oral area. The overall facial improvement of the vitamin C side was statistically significant. Biopsies showed increased collagen formation in the vitamin C group. This study showed that topically applied vitamin C results in clinically visible and statistically significant improvement in wrinkling when used for 12 weeks. This clinical improvement correlated with biopsy evidence of new collagen formation.3


It is well known that destructive alterations in collagen, elastin and glycosaminoglycans contribute to degenerative changes seen in aging skin. A randomized, controlled study was conducted with 53 female volunteers who were supplied with an oral supplement containing glucosamine, amino acids, minerals and various antioxidant compounds. Hydration properties of the skin as well as textural analysis of the women's fine lines and wrinkles were assessed following five weeks intake of the oral supplement and results were compared with those of a control group of 12 individuals who did not take the supplement.

The results showed a statistically significant reduction in the number of visible wrinkles and a reduction in the number of fine lines in the group of women who took the supplement.

This study showed that an oral supplement containing glucosamine, minerals and various antioxidant compounds can potentially improve the appearance of visible wrinkles and fine lines. It did not, however, affect epidermal hydration. Topically applied agents are usually required to keep aging skin moist.*

* Murad H, et al. The effect of an oral supplement containing glucosamine, amino acids, minerals, and antioxidants on cutaneous aging: a preliminary study. J Dermatolog Treat 2001 Mar;12(1):47-51.

Human studies have demonstrated pronounced protective effects of antioxidants when applied topically before ultraviolet radiation exposure. With respect to UVB-induced skin damage, the photoprotective effects of antioxidants are significant. Topical application of such combinations may result in a sustained antioxidant capacity of the skin, possibly due to antioxidant synergisms. Free radicals are a culprit behind UVA-induced skin alterations, thus indicating a basis for topical antioxidant administration. In a human study, topical application of antioxidants resulted in diminished severity of UVA-induced sun damage. Thus, regular application of skin care products containing antioxidants may be of the utmost benefit in efficiently preparing skin against exogenous oxidative stressors occurring during daily life. Sun screening agents may also benefit from combination with antioxidants resulting in increased safety and efficacy of such photoprotective products.4

Collagen is the chief constituent of connective tissue that supports the structure of the skin. The skin requires constant synthesis of new collagen to remain firm and youthful. Epidemiological studies strongly indicate an association between tobacco smoking and skin aging. One study showed that collagen biosynthesis was reduced by 40.1% following treatment with tobacco smoke extract. When an antioxidant mixture that included vitamins C and E were applied, the destructive alteration of collagen induced by both tobacco and UVA radiation was prevented.5

A randomized, double-blind controlled study was conducted on human volunteers to determine the efficacy of topical vitamin C application in treating mild to moderate photodamage of facial skin. Methods of evaluating efficacy included an objective computer-assisted image analysis of the skin surface, subjective clinical photographic analysis, along with patient self-appraisal questionnaires. Topical vitamin C was applied to one side of each patient's face and a control vehicle on the other side for three months.

The results using the optical image analysis demonstrated that compared to the placebo-vehicle, the vitamin C-treated side of the face showed a statistically significant 71% combined score improvement. Clinical assessment parameters demonstrated significant improvement with vitamin C treatment compared to the placebo vehicle for fine wrinkling, tactile roughness, skin laxity/tone, sallowness/yellowing and overall features. Patient questionnaire results demonstrated statistically significant improvement overall with the vitamin C treatment 84.2% greater than control. Photographic assessment demonstrated significant improvement with vitamin C treatment 57.9% greater than control. This three-month study using topical vitamin C provided objective and subjective improvement in photodamaged facial skin.6

Considerable interest has been generated about combining antioxidants with sunscreens to provide enhanced protection against UV rays. Two of the best-known antioxidants are vitamins C and E, both of which have been shown to be effective in different models of photodamage. In a study done on swine skin, vitamin C provided additive protection against acute UVB damage (sunburn cell formation) when combined with a sunscreen. When a combination of vitamins E and C were used, very good protection from a UVB insult occurred. Vitamin C, however, was significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model.7

A study of vitamin C and E in young, aged and photodamaged human skin was conducted to evaluate the various levels of these antioxidants. Compared to young skin, the concentration of vitamin E in the epidermis of photodamaged skin was 44% lower, while aged skin had 39% less vitamin E. There was no difference in the dermis. Vitamin C levels were 31% lower in the epidermis of photodamaged skin and 39% lower in aged skin, while in the dermis region, vitamin C levels were 37% lower in photodamaged skin and 30% lower in aged skin. Glutathione concentrations were also lower. These results showed that the antioxidant defense system in normal aged and photoaged human skin is significantly reduced compared to young skin.8

Chronic inflammation is an underlying cause of common degenerative diseases. One study found that pro-oxidative factors that accelerate skin aging might activate a self-maintained micro-inflammatory process that interferes with skin elasticity and thickness. This study stated that topical antioxidants decrease this inflammatory cascade and thus afford protection to the skin structures.9

The effect of exposure to even ambient UV-irradiation increases the risk for long term detrimental effects characterized by wrinkles, loss of skin tone and resilience. Photoaged skin displays prominent alterations in the cellular component and the extra cellular matrix of the connective tissue. UV-exposure results in an accumulation of disorganized elastin and a severe loss of collagens, the major structural proteins of the dermal connective tissue. The unifying pathogenic agents for these changes are UV-generated free radicals. As well as causing permanent gene mutations, free radicals activate signal transduction pathways that are related to growth, differentiation, senescence and connective tissue degradation.10

Critics used to claim there was no evidence that topically based products affected skin aging. Over the past three years, a remarkable number of published studies have proven these skeptics wrong! The science clearly substantiates the role that free radicals play in causing skin aging and the fact that topically applied antioxidants confer significant protection and can even partially reverse some aspects of skin aging.

Promoting cell renewal

Vitamin A and its retinoid analogs stimulate skin cell renewal by increasing the rate of mitotic cell division.11-13 One mechanism where vitamin A induces this phenomenon is to act as a signaling agent to stimulate the binding of epidermal growth factor to skin cells.12


A report released from Tulane University School of Medicine stated "every patient should topically apply photoprotectants in order to prevent photodamage to the skin."* This report indicates the critical importance of applying a sunscreen with antioxidants every time you go out into the sun.


* Flynn TC, et al. Topical revitalization of body skin. J Eur Acad Dermatol Venereol 2000 Jul;14(4):280-4.

A characteristic of sun-damaged skin is the degradation of the supporting structure of skin caused by reduced collagen synthesis. A study involving 72 individuals of varying age groups was done to see if the topical application of natural vitamin A could improve function in both natural aged, sun-protected and photoaged skin. In one of the study groups consisting of individuals (80+ years of age), topical application of vitamin A for seven days increased fibroblast growth and collagen synthesis, while reducing levels of a collagen degrading skin enzyme (metalloproteinase). The overall findings indicated that naturally aged, sun-protected and photoaged skin share important molecular features including connective tissue damage, elevated metalloproteinase levels and reduced collagen production. Topical vitamin A treatment reduced matrix metalloproteinase expression and stimulated collagen synthesis in naturally aged and sun-protected skin, as it does in photoaged skin.14 Synthetic vitamin A drugs (Retin-A) have shown more profound acute effects in reversing both photo damaged and naturally aged skin, but some people find these drugs irritating to the skin.15

One of the most disfiguring skin diseases is the appearance of cancer. A study was done to compare the effects of dietary administration of a vitamin A drug (13-cis-retinoic acid) to the natural form of vitamin A (retinyl palmitate). Female mice were administered a chemical carcinogen to evaluate the incidence and severity on mouse skin tumor promotion. The results showed that retinyl palmitate inhibited the number and weight of tumors, whereas 13-cis-retinoic acid resulted in a decrease in weight, but not in the number of tumors promoted.16

In another study, tumors were chemically induced in a group of Swiss mice over a 23-week period. The topical application of 13-cis-retinoic acid was compared to natural vitamin A (retinyl palmitate). This study showed that both retinyl palmitate and 13-cis-retinoic acid inhibited the development of skin papillomas and also had a marked effect on skin cancers.17 Vitamin A may be one of the better-documented vitamins to protect against several types of human cancers. One of its mechanisms is to induce healthy differentiation and apoptosis of aged cells. The value of vitamin A in protecting the skin is to help facilitate cell renewal and possibly prevent skin cancers.

Studies show that the upper layer of the skin (epidermis) can be easily loaded with natural vitamin A by topical application. Besides being a precursor for retinoic acid, vitamin A also has a free radical scavenging potential. Vitamin A absorbs ultraviolet light to help protect the most delicate areas of the skin against damaging free radical attack.18 Natural vitamin A thus functions via several pathways to guard against normal and sun-induced skin aging.

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