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Life Extension Magazine

LE Magazine January 2003

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Combating Skin Aging

Going beyond antioxidants

While free radicals have been implicated in much of the damage that occurs to aging skin, there are other injurious factors that result in unsightly structural and functional deterioration.

KEEPING THE
SKIN WELL OILED

Nourishing the skin with topical ingredients is important, but in addition it is essential that you feed your skin nourishing food and drink. That means consuming lots of purified water and minimizing ethanol intake. Aging causes a progressive decline in our ability to internally synthesize the essential fatty acids required by the skin to maintain a youthful, moist appearance. Omega-3 fatty acids can make the skin smoother, softer and look more radiant. When skin is properly nourished, it shows less of the effects of aging. The oral ingestion of fish, flax or perilla oil provides abundant quantities of the omega-3 fatty acids that are so beneficial to the health and appearance of the skin.

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For instance, aging skin cells suffer from metabolic imbalances that preclude them from performing youthful repair functions. The groundbreaking work of Benjamin S. Frank, M.D. showed that RNA improved cellular energy and the ability of the skin's cells to use oxygen. This improved metabolism enhances the movement of young cells to the surface of the skin where they replace old cells.

Another benefit from topically applied RNA is to repair early skin cell damage. Clinical trials by Dr. S.J. Jellinek in the 1970s demonstrated how creams containing RNA/DNA caused a visible lifting/tightening of the skin, and the wrinkles appeared to be less visible in a three-week period. Although the study was a small-scale study, it was nonetheless a double blind test. Very few commercial products provide the potency of RNA and DNA used in these studies.

Glycolic acid is a potent alpha-hydroxy acid that has been shown to erase fine wrinkles in aging human skin. The mechanism of action of glycolic acid is to break down old cells at the skin's surface so they can be replaced with more youthful cells underneath. A 22-week, double-blind, randomized clinical trial at Massachusetts General Hospital in 74 women over age 40 showed that topically applied alpha-glycolic acid significantly reduced wrinkling and other types of damage caused by chronic sun exposure. An alpha-hydroxy acid should be included as a constituent of any anti-aging topical program.

A study in the Journal of Pharmacology and Biophysical Research showed that ginkgo biloba extract signals fibroblast activity in the skin to increase the synthesis of collagen, while serving as an anti-inflammatory agent. Topical application of gingko extract has been found to reduce the irritation that some people experience when using products like Retin-A and highly concentrated fruit acid compounds.

THE IMPORTANCE OF MAINTAINING HEALTHY SKIN

Our skin is the largest organ in the human body weighing approximately ten pounds and covering an area of about 16 sq. ft. People often take skin for granted and tend not to take optimal care of it. Our skin is responsible for protecting our internal organs from the toxic external world. Our skin protects us from heat, cold and physical injuries. It also provides us with sensory information about the nature of the external world, and is our first defense against invasion by bacteria, viruses and other toxic elements. The skin is also an excretory organ, removing toxins from the body via perspiration.

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One of the major problems of advanced aging is the sagging of tissues caused by the destruction of the skin's underlying support structure (primarily collagen and elastin). While much of this structural deterioration may be preventable by lifestyle changes and proper use of oral and topical agents, it is difficult to reverse this unsightly collapse of facial tissues. In a study published in Skin Research Technologies,19 DMAE (dimethylaminoethanol) was shown to produce a firming effect on the skin. This mechanism may be due to the fact that DMAE functions as a cell membrane stabilizer. Based on clinical reports, DMAE may be the first topical agent that can help firm sagging skin.

Keeping the skin moist

Replacing moisture lost to aging is a prime reason why women use face creams. Most commercial face creams are oil-based and work by blocking the release of water from the skin.

As people grow older, however, they cannot rely on oil-based preparations to block the release of moisture. That is because aged skin loses the ability to attract moisture in the first place and fundamentally becomes dehydrated. At this point, aged skin needs to be replenished with its natural moisturizer complex in order to attract and retain water.

The most advanced moisturizer is Ceraphyl® NGA, which functions by reducing the excessive drying in the upper-layers of the skin. Drs. Stig E. Friberg and David W. Osborne showed that Ceraphyl® NGA inhibits trans epidermal water loss by preventing the lipids (fats) from crystallizing. This mechanism is central to preventing dry, thin, leathery, dull, wrinkled skin. Ceraphyl® NGA also seems to increase the effectiveness of sunscreens and enhance the receptiveness of skin cells to antioxidants such as vitamins A, C and E.

THYROID FUNCTION AND SKIN APPEARANCE

People who are deficient in thyroid hormone are often overweight, easily fatigued and mentally depressed. Thyroid deficient individuals also have dry, flaky, sluggish skin. A blood thyroid profile or two-week basal temperature charting can reveal low or borderline low thyroid function. Refer to the Thyroid Replacement Therapy protocol at www.lef.org for information about diagnosing and treating thyroid deficiency.

Hyaluronic acid helps the skin retain its youthful moisture via a different mechanism than Ceraphyl® NGA. Hyaluronic acid maintains the integrity of the connective tissue because it is a source of manganese and glucosamine. Injectable hyaluronic acid may one day replace injectable collagen, but this important skin-preserving nutrient is available without a prescription today in over-the-counter skin creams.

The ability of skin to hold moisture is directly related to its NaPCA (sodium pyrolidone carboxylic acid) content. NaPCA is one of the skin's most important natural moisturizers. Old skin, however, contains only about half the NaPCA as young skin. NaPCA facilitates the moistening by pulling water in out of the air. Optimal protection against age-accelerating dehydration is best obtained by the topical application of NaPCA, hyaluronic acid, lactic acid, urea, Ceraphyl® NGA and squalane every day.

Delivering nutrients to the skin

A concern amongst dermatologists is whether agents that are proven effective in fighting skin aging can be consistently delivered to the specific layers of the skin where they are known to induce their biological effect. The advent of liposome delivery technology has enabled scientists to increase the efficacy of topical anti-aging agents by delivering them into the inner layers of the skin.

A patented liposome delivery system trademarked QuSomes® (meaning "quick liposomes") was discovered in late 2000. This technology represents a substantial enhancement in conventional liposome vehicles. QuSomes® not only delivers active skin protecting ingredients faster into the lower layers of the skin, but these liposomes are also designed to protect the active ingredient from deterioration. With the unique QuSome® delivery system, the solubility of the active anti-aging agents is preserved, thereby enabling them to reside longer in the areas of the skin where they exert their greatest biological effects.

The availability of QuSomes® enables nutrients like alpha lipoic acid to be reliably delivered to the inner layers of the skin. Alpha lipoic acid is a super-potent fat and water-soluble antioxidant. What has scientists so excited about alpha lipoic acid is its role in maintaining the health of the mitochondria, the powerhouses of the cell itself. When the mitochondria are metabolically compromised, skin cells cannot perform youthful repair functions.

In addition, alpha lipoic acid helps turn off an inflammatory messenger known as nuclear factor kappa B (NFkB).The expression of NFkB induces inflammation at an early stage. Factors that suppress NFkB inhibit skin damaging inflammatory processes.20 (Editor's Note: NFk-B is a transcription factor. Transcription factors are messengers found inside the cell, which carry information from the cytoplasm to the nucleus. There they may activate or inhibit the production of certain proteins or enzymes, which then carry out a particular cell function. Such a function might be increased inflammatory factors.)

THE SKIN'S TWO LAYERS

Our skin consists of two main layers-the dermis and epidermis. The dermis is the inner layer of skin that contains nerve fibers, fat cells, blood vessels, sweat and oil glands, and hair follicles. The dermis also contains collagen and elastin, two proteins that are responsible for the structure and elasticity of the skin itself. It is these proteins that are subject to the process of aging. The sweat and oil glands in the dermis protect the outer layer of skin with a thin coating of oil and perspiration.

The epidermis is the very outer layer of our skin. New cells generated by the dermis continually replace this layer. Removal of the epidermis, as in a scrape or burn, reveals an unprotected sensitive dermis underneath.

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Another benefit to having abundant quantities of alpha lipoic acid in the skin is its ability to regulate a collagen-regulating factor known as AP-1. When alpha lipoic acid activates AP-1, it turns on enzymes that digest only glycation-damaged collagen. As we age, proteins become glycated, resulting in the formation of non-functioning cross-linked tissues (advanced glycated end products, AGEs). The accumulation of these cross-links is a hallmark molecular characteristic of visible skin aging.

QuSomes® can deliver alpha lipoic acid deeper into the lower epidermis (top layer) and upper dermis (lower layer) of skin. This makes alpha lipoic acid an exciting new weapon in the battle against the ravages of time.

Summary

Recently published findings indicate that one may have more control over the rate at which their skin ages than any other organ of the body.

To slow skin aging and partially reverse it, an individual must take a comprehensive approach to gain control over all of the factors that have been identified in the skin degeneration process.

For many years, a debate raged in the dermatological community as to whether topically applied anti-aging preparations could slow skin aging. The scientific literature now indicates that the daily application of a variety of agents can have a profound effect on both the health and appearance of the skin.

The next article describes the pioneering work of a medical doctor who developed the first topical preparation that contained ingredients that have now been shown to both protect and restore skin that has been damaged by irradiation and/or normal aging.


References

1. Podda M, et al. Low molecular weight antioxidants and their role in skin ageing. Clin Exp Dermatol 2001 Oct;26(7):578-82.

2. Sander CS, et al. Photoaging is associated with protein oxidation in human skin in vivo. J Invest Dermatol 2002 Apr;118(4):618-25.

3. Fitzpatrick RE, et al. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatol Surg 2002 Mar;28(3):231-6.

4. Dreher F, et al. Protective effects of topical antioxidants in humans. Curr Probl Dermatol 2001;29:157-64.

5. Yin L, et al. Alterations of extracellular matrix induced by tobacco smoke extract. Arch Dermatol Res 2000 Apr;292(4):188-94.

6. Traikovich SS. Use of topical ascorbic acid and its effects on photodamaged skin topography. Arch Otolaryngol Head Neck Surg 1999 Oct;125(10):1091-8.

7. Darr D, et al. Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants. Acta Derm Venereol 1996 Jul;76(4):264-8.

8. Rhie G, et al. Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo. J Invest Dermatol 2001 Nov;117(5):1212-7.

9. Giacomoni PU, et al. Aging of human skin: review of a mechanistic model and first experimental data. IUBMB Life 2000 Apr;49(4):259-63.

10. Scharffetter-Kochanek K, et al. Photoaging of the skin from phenotype to mechanisms. Exp Gerontol 2000 May;35(3):307-16.

11. Ridge BD, et al. The dansyl chloride technique for stratum corneum renewal as an indicator of changes in epidermal mitotic activity following topical treatment. Br J Dermatol 1988 Feb;118(2):167-74.

12. Chapellier B, et al. Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled. EMBO J 2002 Jul 1;21(13):3402-13.

13. Koussoulakos S, et al. Effect of vitamin A on wound epidermis during forelimb regeneration in adult newts. Int J Dev Biol 1990 Dec;34(4):433-9.

14. Varani J, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degradingmatrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol 2000 Mar;114(3):480-6.

15. Varani J, et al. Molecular mechanisms of intrinsic skin aging and retinoid-induced repair and reversal. J Investig Dermatol Symp Proc 1998 Aug;3(1):57-60.

16. Gensler HL, et al. Effects of dietary retinyl palmitate or 13-cis-retinoic acid on the promotion of tumors in mouse skin. Cancer Res 1987 Feb 15;47(4):967-70.

17. Abdel-Galil AM, et al. Prevention of 3-methylcholanthrene-induced skin tumors in mice by simultaneous application of 13-cis-retinoic acid and retinyl palmitate (vitamin A palmitate). Exp Pathol 1984;25(2):97-102.

18. Sorg O, et al. Cutaneous vitamins A and E in the context of ultraviolet- or chemically-induced oxidative stress. Skin Pharmacol Appl Skin Physiol 2001 Nov-Dec;14(6):363-72.

19. Uhoda I, et al. Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol (deanol) gel. Skin Res Technol 2002 Aug;8(3):164-7.

20. Saliou C, et al. Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med 2001 Jan 15;30(2):154-160.


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