The Science of Keeping
Your Skin Young
By Will Block

Play me a nocturne, Dorian, and, as you play, tell me, in a low voice, how you have kept your youth. You must have some secret. I am only ten years older than you are, and I am wrinkled, and worn and yellow.

- Oscar Wilde, The Picture of Dorian Gray

hat is the first thing you usually notice about someone when guessing their age? It's their skin, of course. The skin is the battlefield of life. If someone's had a hard time or if they've been in a lot of pain - psychologically or physiologically - you can see it in the foxholes and trenches of their skin. The condition of the skin is an important indication of how individuals treat themselves. Do they get enough rest? Do they eat a reasonable diet? Do they abuse drugs, coffee, alcohol, or food? Are they happy? You can see it in their skin - often their whole history - because the skin is the most visible and expressive marker for biological age.

To be able to do something about skin aging - to slow it, stop it, or even reverse it - it is necessary to analyze how the skin is affected by wear and tear, by oxidative stress, and by the spectrum of environmental assaults, especially sun exposure.

Crucial to this analysis is an understanding of the molecular biochemistry of skin aging. It is this level of analysis that forms the basis of two new personal care products from life extension scientists Durk Pearson & Sandy Shaw. As you will see, these products are far from mere skin lotions; they are true antiaging agents.

WHAT'S OBVIOUS?
Among the most common measures of biological age (and the ones that lend themselves to direct observation) are skin elasticity and graying of the hair (a form of skin). So it is not altogether surprising that in one of the earliest studies attempting to correlate chronological age and physiologic testing, these two measures were highest in rank.1 Yet, other telltale signs also indicate a decline in physiologic function:

  • Sagging skin
  • Rough skin texture
  • Wrinkles
  • Dyspigmentations (age spots)

Without question, all of these and other manifestations of skin aging affect appearance and consequently self-image. Indeed, those people whose skin appears to be older than their years often tend to be less physically healthy overall than those who maintain more youthful skin. While wrinkles, inelasticity, and roughness can be visually disturbing, they often reflect far more serious consequences - the progressive alteration in the physiological function of skin with age. When this decline continues, the skin's molecular mechanisms break down. They can no longer adapt to external changes in the environment, and the consequence is an increased likelihood of skin diseases.

SAFE SUN BATHING
Clinical studies indicate that for most people, 50% of their ultraviolet (UV) light exposure occurs before the age of 18 years.2 Scientists estimate that repeated and prolonged unprotected UV exposure has resulted in a large photodamaged population and an epidemic of malignant melanoma, the most dangerous form of skin cancer. It is estimated that in the next 4 years skin cancer will become the most common type of cancer, and malignant melanoma will become the leading cause of death from skin cancer.

FREE-RADICAL DAMAGE
We now know that the principal mechanism of damage from UV exposure is the hyperreactive generation of free radicals. A recent human cell study demonstrates that one of the effects of free-radical damage is an abnormal alteration in the mRNA expression of elastin, a substance that contributes to skin elasticity. An endogenous antioxidant scavenger, catalase, essentially prevents the free-radical-induced changes in elastin mRNA levels, suggesting the role antioxidants can take in repealing some of the results of skin photoaging.3

DISEASES OF THE SKIN
Indeed, studies have found that as people age, skin diseases, and other skin conditions significant enough to send someone to seek medical assistance increase. A large survey conducted in the early 1970s of more than 20,000 subjects found that 66% of those aged 70 or older required the attention of a physician for their skin conditions.

But before matters reach out-and-out pathology that mandates medical attention, early signs appear indicating that the skin's self-defense system is breaking down. One study showed a significant increase in specific skin changes that are usually not serious enough to warrant treatment, but which are often a prelude to more severe conditions.5 The authors included among these conditions:

  • Loss of elasticity (found in 94% of those over age 64)
  • Comedones - the typical skin lesions of acne vulgaris (found in 81% over age 64)
  • Seborrheic keratoses - benign crusty skin tumors which may be pigmented (found in 80% over age 64)
  • Xerosis - abnormal dryness of skin (found in 77% over age 64), and
  • Cherry angiomata - tumors, usually benign, involving blood vessels (found in 75% over age 64)

LOST IMMUNITY
As the skin's adaptive capability wanes with age, so does its vital immune function. In studies of both humans and animals, age-related immunosenescence results in an increased susceptibility to certain infections, autoimmune diseases, or malignancies.6 With age, T cells and other cell-mediated immune mechanisms lose their ability to stem abnormal proliferation. Because of somatic mutations, B cells also are restricted in their antibody activity. The result of these changes is a reduction in defensive responses to certain viral infections or vaccinations. Also with age, the number of Langerhans cells - the principal antigen-presenting cells in the epidermis - decline, contributing to reduced sensitization that results, in turn, in the body's inability to distinguish between contact allergens and skin irritants Other key immune components that undergo change with age include antigen-ingesting macrophages and structure-enhancing keratinocytes with consequent alterations in cytokine production. Cytokines are instrumental in regulating immunological aspects of cell growth and function.These losses that occur in immune function with age may explain the increased susceptibility of the elderly to endotoxins, also called intracellular toxins.

CAROTENOIDS
In addition to a loss of elasticity, chronological aging of the skin is accompanied by a slowdown in metabolic activity. When environmental or UV-induced irradiation damage is superimposed on the intrinsic aging process, the result is a thickened epidermis and increased production of melanin, the natural skin pigment that absorbs and protects against the UV components of sunlight. In the dermis, massive buildup of abnormal elastic fibers, collagen degeneration, and convoluted and dilated microvasculature also occur. Although regular use of a sunblock appears to allow some repair as well as protection from further photodamage, it is not enough.

Fortunately, topically applied carotenoids have been shown to help reverse these clinical and histological changes caused by sun and aging.7,8,9 Carotenoids inhibit proliferative growth of melanocytes and melanoma cells. They affect pigmentation disorders - both the hypo- and hyper- varieties - altering the endogenous concentration of retinoids between benign and malignant melanocytes. In so doing, they are thought to play a key role in cell differentiation and growth regulation.10 Although a great deal of recent work suggests that retinoids can help prevent development of basal cell cancers, their mechanism of action remains unknown.

One of the mechanisms suggested has been an alteration in gap junctions, which results in a deterioration of cell-to-cell communication. In one study, topical carotenoids produced a doubling in gap junction density,11 thought to help prevent abnormal proliferation which can result in carcinogenesis.

ALPHA HYDROXY ACIDS
Long observed to operate as astringents and exfoliants in their native forms (e.g., milk baths used by Cleopatra, old wine use by French nobility in the 17th and 18th centuries, and sugar cane used by Polynesian women), alpha hydroxy acids (AHA) continue to show new benefits. Not only can frequent regular use of personal care products containing AHA moisturize the skin and produce smoother, less-wrinkled skin surfaces, it can also diminish skin scales, remove excess skin oil, and improve photo-damaged skin.12 At the same time, these compounds have been reported to normalize hyperkeratinization, which can produce acne, increase epidermal thickness, and enhance production of dermal glycosaminoglycans that are important for wound healing. The single randomized controlled study now available appears to substantiate AHA efficacy and safety.13

ARGININE PCA
When PCA, the salt of pyrrolidone carboxylate, is applied topically to the skin, it has been found to enhance the moisturizing ability of skin.14 When the amino acid arginine, which can be bound to PCA, is topically applied to skin, it operates as a growth factor, serving to increase levels of vascular endothelial growth factor (vegF), thought to be the body's signal to grow new blood vessels.15 Growing excitement in the world of gene therapy (the audience at a recent American Heart Association in Orlando, FL was left breathless) has to do with the use of in vivo gene-switching technology to increase production of vegF, and cause the body to bypass hopelessly blocked blood vessels. In 9 out of 10 patients given this therapy, the results were clear, with three patients even avoiding scheduled amputations!16

Arginine is also a very powerful antioxidant, and a superb "sacrificial target" for Maillard type cross-linking reactions.17 These reactions constitute one of the major aging mechanisms that take place in the skin, where activated carbonyl groups, such as aldehydes, react with the amino groups in proteins to produce Maillard products, some of which are carcinogenic.18 The Maillard products then undergo further reaction, which is irreversible and results in end-stage glycosylation products. Enzymes that have been glycosylated don't work right, if they work at all, and the result is "age spots," lost elasticity and the inability to transfer nutrients across membranes. The higher your level of blood sugar, the faster this glycosylation reaction occurs. The most severe form of this reaction occurs in people who are diabetic and have high levels of blood sugar. Arginine can successfully block this glycosylation process.

WHAT THE CHEF ORDERED
The good news is that carotenoids, alpha hydroxy acids, the arginine salt of PCA and many other ingredients are contained in the revolutionary skin care products designed by Life Extension authors and scientists Durk Pearson and Sandy Shaw. These formulations are the result of Durk and Sandy's heroic efforts to understand the work of hundreds of scientists, their own innovative thinking over the last 2 decades, and thousands of hours of time spent in the lab. Intended to complement each other, you simply must try them to believe what they can do for you.

References

  1. Hollingsworth JW, Hashizuma A, Jablon S. Correlations between tests of aging in Hiroshima subjects. Yale J Biol Med. 1965;33:11.
  2. Bergfeld WF. The aging skin. Int J Fertil Womens Med. 1997;42:57-66.
  3. Kawaguchi Y, Tanaka H, Okada T, Konishi H, Takahashi M, Ito M, Asai J. Effect of reactive oxygen species on the elastin mRNA expression in cultured human dermal fibroblasts. Free Radic Biol Med. 1997;23:162-165.
  4. Johnson MLD, Roberts J. Prevalence of dermatological disease among persons 1-74 years of age. US Advance Data No. 4, US Department of Health, Education and Welfare, Washington DC 1977.
  5. Tindall JP, Smith JG. Skin lesions of the aged and their association with internal changes. JAMA. 1963;186:1039.
  6. Sunderkotter C, Kalden H,Luger TA. Aging and the skin immune system. Arch Dermatol. 1997;133:1256-1262.
  7. Goffin V, Henry F, Pierard-Franchimont C, Pierard GE. Topical retinol and the stratum corneum response to an environmental threat. Skin Pharmacol. 1997;10:85-89.
  8. Lundin A, Berne B, Michaelsson G. Topical retinoic acid treatment of photoaged skin: its effects on hyaluronan distribution in epidermis and on hyaluronan and retinoic acid in suction blister fluid. Acta Derm Venereol. 1992;72:423-427.
  9. Salagnac V, Leonard F, de Lacharriere O, Le Corre Y, Kalis B. Treatment of actinic aging with topical vitamin A acid in different concentrations. Rev Fr Gynecol Obstet. 1991;86:458-460.
  10. Rosdahl I, Andersson E, Kagedal B, Torma H. Vitamin A metabolism and mRNA expression of retinoid-binding protein and receptor genes in human epidermal melanocytes and melanoma cells. Melanoma Res. 1997;7:267-274.
  11. Elias PM, Grayson S, Gross EG, Peck GL, McNutt NS. Influence of topical and systemic retinoids on basal cell carcinoma cell membranes. Cancer 1981;48:932-938.
  12. Vidt DG, Bergfeld WF. Cosmetic use of alpha-hydroxy acids. Cleve Clin J Med. 1997;64:327-329.
  13. Stiller MJ, Bartolone J, Stern R, Smith S, Kollias N, Gillies R, Drake LA. Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin. A double-blind vehicle-controlled clinical trial. Arch Dermatol. 1996;132:631-636.
  14. Lin SY, Duan KJ, Lin TC. Direct or indirect skin lipid-ordering effect of pyrrolidone carboxylate sodium after topical treatment with penetration enhancers. Biomed Mater Eng. 1995;5(1):9-20.
  15. Fujii E, Irie K, Ohba K, Ogawa A, Yoshioka T, Yamakawa M, Muraki T. Role of nitric oxide, prostaglandins and tyrosine kinase in vascular endothelial growth factor-induced increase in vascular permeability in mouse skin. Naunyn Schmiedebergs Arch Pharmacol. 1997;356:475-480.
  16. Kolata G. Gene therapy gives blood a path around leg blockages, researchers say. New York Times. Nov. 10, 1997;14.
  17. Fu MX, Wells-Knecht KJ, Blackledge JA, Lyons TJ, Thorpe SR, Baynes JW. Glycation, glycoxidation, and cross-linking of collagen by glucose. Kinetics, mechanisms, and inhibition of late stages of the Maillard reaction. Diabetes. 1994;43:676-683.
  18. Graham L. A comprehensive survey of the acid-stable fluorescent cross-links formed by ribose with basic amino acids, and partial characterization of a novel Maillard cross-link. Biochim Biophys Acta. 1996;1297:9-16.

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