Because sleep is essential to preserve and restore skin's health and healthy appearance, it is crucial to establish and maintain a healthy sleep pattern and to recognize sleep as the most significant window of opportunity for reparative intervention through topical and internal delivery of potent anti-aging ingredients.

Theoretical explanations connecting loss of sleep to disease processes include the theory that the loss of cellular and tissue repair time results in multiple homeostatic imbalances that have a significant adverse impact on all systems. The consequences of sleep induced imbalances on the skin include:

• Elevated secretion of cortisol which can cause: inhibition of protein synthesis (including collagen production in skin); increased water loss and suppression of the immune system
  
  
• Decreased secretion of the human growth hormone (hGH) which has negative impact on cell proliferation and tissue repair
  
  
• Increased disturbances in skin barrier homeostasis, damage to stratum corneum integrity, inhibition of synthesis of epidermal lipids and delayed barrier recovery

The end result of these adverse impacts is intracellular and connective tissue water loss – the ultimate pathway of aging as predicted by The Science of Cellular Water.™ Adverse skin changes are apparent: more pronounced fine lines and wrinkles; lack of elasticity, contractility and architectural regularity; sallow tone, under-eye dark circles and puffiness; dryness and

Repair Enhancing Matrix (REM) was developed to work during sleep to encourage faster and more complete skin repair while providing antioxidant protection to shield cells from further damage. To that end, the agents in the REM formula specifically act to relax skin tension, reduce wrinkle depth, improve collagen synthesis and enhance elasticity.

Both topical and internal versions of Repair Enhancing Matrix (REM) contain 3 potent agents:

In order to investigate the anti-aging potential of REM, topical and internal formulas combining REM with other agents were created. Both formulas included ingredients that encourage the onset of a fundamental resting state conducive to significant cellular renewal. The paired agent was Melatonin, the principle hormone produced by the pineal gland to help regulate the body's sleep-wake cycle, mental alertness and body temperature.

Because natural Melatonin production decreases with age and exposure to high levels of artificial light, insufficient levels of Melatonin often contribute to insomnia and poor sleep quality. Accordingly, Melatonin supplementation as a therapeutic modality for inducing and regularizing sleep is well established. Melatonin was selected as the featured additive in these formulas because of its efficacy as a soporific, its freedom from significant counter-indications and its powerful antioxidant activity.

On a cellular level, the investigation reveals a recovery of optimal intracellular and connective tissue water content. Visually, healthy skin color is reestablished, texture is refined, skin is firmer, more voluminous and the number and depth of fine lines and wrinkles are reduced.

Because sleep is essential to preserve and restore skin's health and healthy appearance, it is crucial to establish and maintain a healthy sleep pattern and to recognize sleep as the most significant window of opportunity for reparative intervention through topical and internal delivery of potent anti-aging ingredients.

The combination of Repair Enhancing Matrix (REM), Melatonin and other multifunctional agents does enhance the nightly skin repair process by producing clinically distinct, anti-aging benefits while optimizing and regularizing sleep.

REM, the night-specific Repair Enhancing Matrix™ makes the most of skin's restorative hours. This patent pending formula adds depth and power to skin's natural sleep repair cycle and dramatically reduces the signs of aging with ingredients that have been shown to improve collagen production. Repair Enhancing Matrix accelerates skin barrier recovery and protects barrier homeostasis while enhancing the penetration of other ingredients. REM infuses skin with powerful anti-inflammatory and photoprotective agents while promoting skin epithelization- the collagen synthesis needed for firmer, stronger, younger-looking skin.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Specific hormonal disturbances that become manifest during perimenopause, menopause and postmenopause have a significant and perceptible impact on the aging process. Clinical manifestations of these disturbances in the skin include development of fine lines and wrinkles, dryness, textural irregularities, loss of luminosity and brightness, reduced elasticity and firmness, and an increase in acne breakouts. The negative dermal and epidermal consequences associated with the hormonal aging syndrome can be successfully addressed through application of formulas with multifunctional actives specific to the evolution of hormonal skin aging on both the cellular and macroscopic levels.

Beyond the commonly recognized gross clinical manifestations of the menopause phase of hormonal aging syndrome (such as vasomotor episodes—"hot flashes," night sweats, sleeping disturbances, severe tiredness, stiff joints, body pain, headaches, urogenital symptoms, mood changes and lower self-esteem), hormonal aging has an influence on both skin development and composition that begins subtly but becomes quite profound over time.

Hormone receptors specific to estrogens and other hormones have been detected throughout the skin in keratinocytes, fibroblasts, sebaceous glands, hair follicles, sweat glands and blood vessels. These receptors are sites where hormones are received and bind to cellular structures—a process that stimulates a specific cellular response, for example, production of collagen. Because of the role hormones play in triggering these skin building responses, adequate levels of hormones are required to maintain the skin's structural integrity and functional capacity. In clinical terms, as a result of diminishing levels of estrogen, women experience symptoms of skin aging that become more pronounced as the hormonal aging syndrome moves toward menopause. Hormonal aging is associated with:

• Skin dehydration (dryness and roughness) caused by a decrease in the capacity of the stratum corneum to retain water as well as a reduction in levels of mucopolysaccharides and hyalouronic acid in the dermis and epidermis
• Decreased epidermal cell adhesions, migration and differentiation
• Decrease in size, number and activity of sebaceous glands
• Flattening of the dermal-epidermal junction
• Degradation of collagen, elastic tissue, dermal matrix ( i.e., glycosaminoglycans, proteoglycans) and fibroblasts in the dermis, with consequent loss of elasticity and distensibility, accompanied by a progressive deepening of facial creases and wrinkling
• Manifestations of hyperandrogenism (excessive secretion of male hormones) such as acne breakouts and hirsutism (excessive growth of facial or body hair)
• Poor wound healing
• Overall thinning of the skin, resulting in pronounced transparency and fragility
• Loss of subcutaneous fat, resulting in less resiliency and less cushioning against assault

The histological and clinical changes seen in skin as a result of the hormonally aging syndrome are predicted and explained by The Science of Cellular Water,™ Dr. Howard Murad's hypothesis of aging. Dr. Murad's theory looks at the impact of the hormonal aging syndrome on hydration at the macro and micro level for markers of skin health. In the stratum corneum, hormonal depletion causes skin barrier disruption and an increase in transepidermal water loss (TEWL). In deeper layers of skin, hormonal depletion can be seen as the root cause of cell membrane and connective tissue deterioration. This deterioration increases cellular water loss which can be detected by visual and tactile evaluation as signs of aging.

A unique combination of select phytoestrogens with multifunctional ingredients that possess robust hydrating and nourishing properties may prevent and reverse signs of hormonal skin aging by reestablishing moisture level, lipids and cellular profile typical of young skin.

A unique proprietary blend of phytoestrogens with multifunctional ingredients, which possess robust hydrating and nourishing properties, induces clinically significant improvements in all main visual aspects of hormonally aging skin.

Skin aging is a continuous, multifaceted process. Intrinsic, or genetic, aging normally begins in our mid-20s. Deoxyribonucleic acid, DNA, controls how quickly the naturally occurring functional decline in aging skin unfolds. Extrinsic, or environmental, aging commences with the skin's first exposure to its main causes such as UV rays, pollution, trauma and unhealthy lifestyle, including poor nutrition, cigarette smoke, alcohol consumption and stress, among others. Visual consequences of skin aging appear gradually but incessantly. Skin becomes thin, transparent, loose, dry and rough. Over a lifetime, fine lines and wrinkles, irregular pigmentation, uneven complexion, redness and telangiectasia develop. Multifunctional ingredients, like Durian Cell Reform, are necessary for intensive topical prevention and reversal of visible skin aging.

The unique polysaccharide, lipid and sulfur-rich fractions of Durian combine to create optimized cell water homeostasis following natural cell turnover initiated by alpha hydroxy acids.

Skin aging is a consequence of many simultaneous and unrelenting events.

In the epidermis, corneocytes do not desquamate as frequently and the skin barrier function is easily compromised. At the same time, cell proliferation decreases, senescence keratinocytes accumulate mutations (cell damage) and start to significantly vary in size and shape. The epidermis becomes thinner and the dermal-epidermal junction flattens, hindering the communication and nutrient transfer between the layers.

In the dermis, atrophy, or loss of dermal thickness, and gradual destruction of the dermal fibers' network progress due to a decline in the number of fibroblasts, collagen and elastin synthesis slows and fibers appear more disorganized. Biochemical changes in collagen and elastin, including a decrease in the ground substance, consisting of glycosaminoglycans, proteoglycans and mucopolysaccharides, lead to increased skin rigidity. Reduction in the vascular network affects supply of water and nutrients to the skin.

Overall, repetitive oxidative stress, caused by free radical activity, weakens antioxidant defense systems and DNA repair capacities in the skin with consequent accumulation of damaged cellular lipids and proteins and lack of healthy skin constituents. Increased levels of pro-inflammatory cytokines caused by oxidative stress contribute to cell membrane and connective tissue damage. The end result a rapid decline of water content within skin cells and connective tissue as proven by The Cellular Water Principle®.

The Durian plant contains an abundance of flavonoid antioxidants as well as numerous compounds containing a chemical element that is essential to cell membrane health—sulfur. Sulfur donors are critical to protect the cell membrane and provide vital nutrients used by the body to produce free radical fighting antioxidants. Over 100 sulfur-containing ingredients have been identified in Durian. These components act with minerals (Copper, Manganese and Potassium) and vitamins (Vitamin C, Niacin and Vitamin B-6) found in the Durian plant to bolster cell membrane integrity, provide protection from free radicals and other environmental stressors and aid in maintaining cellular water balance.

Analytical studies done by leading plant lipid, polysaccharide and antioxidant chemists supplemented by over twenty years of clinical research by Dr. Murad with hydroxy acids are combined in Durian Cell Reform to optimize cellular water homeostasis. Durian Cell Reform contains the same key components that provide the Durian fruit, and now our cells, with the immense health benefits of homeostatic cellular water balance.

Durian Cell Reform™ is a proprietary blend of Durian Extract and Glycolic Acid that forms synergistic cell turnover and active ingredient delivery system. The Durian seed contains numerous fatty acids – notably, palmitic, oleic and linoleic acids, as well as other valuable fruit acids, including malic acid. Durian Cell Reform enhances the activity of these ingredients by adding clinically proven amounts of Glycolic Acid. This combination increases the rate of natural cell turnover while exposing new cells for enhanced penetration of Age Reform Intensives active ingredients; UGL Complex, Glucosamine, Hyaluronic Microspheres, Dried Plum Extract and Vitamin C, as well as the intensive hydro-protection of Durian's active ingredients, trehalose and polygalacturonic acid.

Provide your cells with the foundation for a lifetime of healthy, beautiful skin.

Skin health is preserved by optimal biological responses to a variety of antagonists. Synergistc action of repair mechanisms (e.g. keratinocytes or fibroblast proliferation, collagen production, restitution of dermal matrix, etc.) and immune defense system is necessary for optimal biological response. Skin aging is characterized by a decline in the ability to respond to and defend against UV rays, pollution, poor nutrition, cigarette smoking, alcohol consumption, stress, and other degrading factors.

During the aging process, immune function declines dramatically, adversely affecting the skin's ability to repair and defend itself. Advances in biotechnology have led to the discovery of peptides (bio-peptides, analogues of natural peptides) formulated to enhance intercellular communication, optimize skin immunity and stimulate the growth factors that regulate skin cell proliferation and dermal matrix remodeling.

Immuno-Skin Complex™ may assist in modulating the signs of advanced skin aging by stimulating skin immunity and up-regulating proliferative growth factors and cell proliferation.

The human immune system is not a single system, but instead a complex constellation of responses to attacks from outside the body. It has many facets, a number of which constantly adapt to optimize the biological defenses necessary to prevent infection, disease and other unwanted invasions. The skin is a critical outpost of the immune system because it provides control of local immune processes and influences systemic immunity. Both Langerhans cells and keratinocytes within the skin are able to trigger a bodywide immunologic response.

The skin is affected by a variety of negative factors that can weaken its immune system and may ultimately adversely affect systemic immunity. These factors include pathogens, toxic substances, trauma, UV exposure, poor nutrition, prolonged stress and many other aspects of an unhealthy lifestyle, all of which damage healthy skin, increasing the incidences of skin disorders and age-related changes.

The skin's epidermis is primarily composed of keratinocytes and specialized immune cells called Langerhans cells. Both the Langerhans cells (antigen-presenting cells) and the keratinocytes are involved in the immunological processes. The Langerhans cells are the primary immunological cells within the epidermis and are counterparts to the macrophages located in the dermis, providing dermal immunological function. The Langerhans cells play a vital role in sustaining skin integrity by recognizing aggressors and providing defensive and regulating functions.

Keratinocytes are also immunocompetent skin cells and play an irreplaceable role in modulating skin immune responses. Keratinocytes have been shown to promote T-cell lines (white blood cells) and subsequently enhance antibody production. Keratinocytes provide this important immune response through cellular signals produced by cytokines. Cytokines are a group of proteins and peptides that mediate intercellular communication. These signaling chemicals include interleukins, monokines, interferons, EGF (epidermal growth factor), FGF (fibroblast growth factor), TGFa (transforming growth factor alpha) and numerous others.

When skin is assaulted, immunocompetent skin cells are triggered to defend and repair skin damage. The skin is flooded with a complex of cytokines and growth factors, which function as “messenger molecules” to stimulate cellular proliferation and restore normal skin function.

However, as we age and expose our skin to adverse external factors, our immune system's ability to create messenger molecules that send a “distress signal” in response to ongoing assaults and challenges declines. Therefore, topically applied immunostimulating compounds such as bio-peptides and other bioactive ingredients can provide a new therapeutic defense for immunocompromised skin against age-related changes.

The objective of the investigative studies was to evaluate the immunostimulating and dermal matrix enhancing properties of the proprietary Immuno-Skin Complex™ comprised of highly active bio-peptide sequences
Leu-Gln-Gly-Glu-Glu-Ser-Asn-Asp-Arg or L-Glu-Hist to:
(1) Help strengthen the skin's immune modulating properties against external and internal factors and
(2) Upregulate the production of specialized growth factors essential to cellular proliferation and tissue remodeling.

Keratinocytes were cultivated in vitro for several days and baseline measurements of EGF (epidermal growth factor) and KGF (keratinocyte growth factor) were evaluated. The commercial ELISA (enzyme-linked immunosorbent assay) test systems were used to measure the quantity of growth factors and interleukins. The PCR (polymerase chain reaction) was used to measure gene expression. The number of mRNA copies started to increase within 10-15 minutes after the introduction of the bio-peptide sequence Leu-Gln-Gly-Glu-Glu-Ser-Asn-Asp-Arg in cell culture. Keratinocyte cultures exposed to the bio-peptide increased the expression of keratinocyte growth factor (KGF) and epidermal growth factor (EGF).

Immunostimulant activity of bio-peptide sequence L-Glu-Hist was tested in vitro on murine splenocytes and human lymphocytes population. The cell proliferation was followed by measuring indicators of DNA synthesis. For both types of tested cells, L-Glu-Hist significantly amplified DNA synthesis and cell proliferation. Cytostimulating properties of the L-Glu-Hist were tested on human fibroblast cultures. Results confirmed significant stimulating abilities of L-Glu-Hist on artificially aged fibroblasts.

Immuno-Skin Complex™ induced the synthesis of specialized growth factors and cytokines in vitro, which demonstrates its potential to enhance skin immunity, facilitate cellular proliferation and subsequent tissue rejuvenation.

Dr. Howard Murad, the world renowned dermatologist who revolutionized the world of professional esthetics with Alpha-Hydroxy Acids introduces a new, groundbreaking way to fight skin aging – Immuno-Skin Complex.™

Immuno-Skin Complex™ is comprised of immune modulators that help boost the skin's defenses to fight the signs of future skin aging and next generation peptides to repair existing damage. Immuno-Skin Complex™ helps stimulate the skin's own immune response system to defend against the contributing factors of skin aging.

This latest innovation from Dr. Murad, found exclusively in Murad® Professional products, is an outgrowth of his continuing research into the way in which cellular water loss and the resulting connective tissue degradation are responsible for the skin damage we attribute to aging. This research into The Cellular Water Principle® is the foundation for every product developed by Murad.

Wrinkles are just one of several signs of skin aging that affect individuals over their lifetime. Fortunately, the visible signs of skin aging can be prevented and in many cases reversed.

Skin aging is a complex subject with numerous theories proposed to explain its dynamics and mechanism. The two most widely accepted causes of skin aging are internal factors and external factors, herein referred to as genetic skin aging and environmental skin aging.

Genetic skin aging is determined by our predisposition and is characterized by changes within the skin occurring over time. Environmental skin aging is caused by sun exposure, cigarette smoking, alcohol consumption, poor nutrition, stress, pollution and gravity. Although distinct in definition, our skin is generally affected by both genetic and environmental factors.

In aging skin, the most profound changes occur within the structure of the dermis, evidenced by collagen and elastin degradation, decreased production of naturally occurring carbohydrates (glycosaminoglycans and polysaccharides) and cellular water loss.

The loss of structural collagen and elastin proteins causes skin to lose its firm, wrinkle-free appearance and ability to snap back into place. The naturally occurring carbohydrates which contribute to skin density, volume and essential hydration also diminish with the aging process. What's more, dead surface skin cells do not desquamate as frequently leading to cellular retention.

Conclusively, wrinkles are one of the several clinical signs of genetic and environmental skin aging. Other age-related signs include dyschromias (age spots), epidermal thinning, loss of elasticity and barrier dysfunction.

Replicating the constituents of healthy skin may assist in the reversal of age-related changes associated with genetic and environmental skin aging.

The data concludes Murad Intensive Wrinkle Reducer significantly reduced the appearance of fine lines and wrinkles, improved skin tone, hydration and texture over an eight-week period.

Clinical Assessment of Intensive Wrinkle Reducer:

• Skin firmness increased up to 40% within ten minutes
• Skin tone improved up to 25% after eight weeks
• Skin hydration increased up to 37% after eight weeks
• Fine lines and wrinkles decreased up to 45% after eight weeks

* Data on file. Individual results may vary. Eleven subjects participated and all completed the study. No subject dropped out due to adverse reactions to the product.

Photographic Assessment of Intensive Wrinkle Reducer

GlycoNutrient Complex is a water-soluble, bioengineered aggregate of Glycosaminoglycans, Glucosamine, marine-derived Polysaccharides, Linoleic Acid and Glycolic Acid, which have been shown to activate epidermal cells resulting in increased cellular turnover and proliferation. Clinical studies demonstrate the complex provides epidermal resurfacing without irritation while significantly increasing skin firmness. Intensive Wrinkle Reducer also includes a Lipo-Amino Acid containing Cinnamon Extract to improve skin imperfections revealing clearer, more radiant skin. In addition, this exclusive formula contains antioxidants, water-binding humectants, lipids and skin protectants that improve barrier function and protection against future skin damage.

Intensive Wrinkle Reducer® is a daily skin regenerating treatment scientifically proven to dramatically diminish the visible signs of skin aging.

A breakthrough in anti-aging technology, Intensive Wrinkle Reducer contains the GlycoNutrient Complex.
This revolutionary complex has been clinically proven to regenerate the skin's appearance, thereby providing skin resurfacing without irritation while increasing skin firmness. This targeted, fast acting formula begins to work in just
10 minutes with more dramatic results with continuous use.

The breakthrough technology of Intensive Wrinkle Reducer delivers a potent synergy of age defying ingredients providing both immediate and long-term results. Daily use will dramatically diminish the appearance of fine lines and wrinkles and reveal firmer, smoother and more even-toned skin.