Dr. Howard Murad, M.D.

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Skin Immunity - The New Anti-Aging Frontier
By Howard Murad, M.D.

As the famed Nobel Laureat, Albert Szent-Gyorgi Von Nagyrapolt said, “Discovery is seeing, what everyone else has seen and thinking what no one else has thought.”

Scientific breakthroughs are rarely sudden and skincare discoveries are no exception. After working my way through medical school as a pharmacist, I found that research and compounding formulas were something I was very passionate about.  Upon opening my medical practice in 1972, I started working closely with a cosmetic chemist, creating topical skincare blends to answer my patient’s individual needs.  By the mid-80’s, when Glycolic Acid was a foreign substance to most, I had already tested various AHA’s on over 10,000 people, in search of ways to improve their acne, hyperpigmentation and wrinkles.  Introducing the concept of AHA’s was not always easy, and I often heard, “What, you’re going to put acid on my face?”  A few years later, AHA’s became the industry standard for chemical exfoliation in the esthetic community. The introduction of these cosmeceuticals helped to propel the professional skincare market to the successful field it is today.

Beyond Cosmeceuticals

These topical solutions have prevailed, however the ideal client care goes beyond just topical care. We must not treat the skin in isolation. It is our body’s largest organ and responds best with an “Inclusive” approach to maximize its full potential.  Providing inclusive care means addressing skin from the inside out, with foods and Internal Skincare® nutrients.  An Inclusive approach also involves emotional health and lifestyle changes that reduce stress and isolation.  And the underlying goal to every Inclusive Health® program is to boost cellular water; I call this the Cellular Water Principle™.  Its basic precept is simple: when our cells and connective tissue are not fully hydrated, they cannot function at their optimal level. This leads to tissue damage we refer to as aging, and to dehydration that results in cell deterioration.  When cells and connective tissue are filled with water, they are strong and can prevent the onslaught of disease and aging.

Addressing the “whole’ body is where the future lies in our industry. During the last few years of studying the skin, I have observed that even under great assault, from microbes, chemicals, and other environmental agents, the skin is resilient; it bounds back and wards off infection.  This means there is a sophisticated defense system at work, maintaining balance and protection.  Through this research, I’ve discovered the important connection between immunity and the skin.

When people hear the word immunity, their initial thoughts often gravitate towards vaccines, white blood cells, and infectious diseases. However, the body’s first and most influential line of immunity defense is the skin. By improving the integrity of the skin’s immunity, the body can be better protected by diseases, while also reducing the visible signs of aging.

The Skin and Other Body Systems

The human body is a complex organization. Every system of the body is connected to each other and must support each other to sustain life.  These systems include:

• Circulatory – consists of the heart, arteries and veins, for blood flow.
• Digestive – includes the stomach and intestines to process food into minerals, amino acids and glucoses and passes them to the circulator system for delivery.
• Endocrine – includes the pancreas and pituitary glands which release hormones to control metabolism, growth and development, tissue function and mood.
• Urinary – includes the kidneys and bladder to filter out waste products from the blood and flush waste products from the body.
• Lymphatic – includes the spleen and thymus to help remove foreign matter from body fluids.
• Muscular – includes all muscle tissue and cardiac connective tissue which provide control and movement in other organs.
• Nervous – includes the brain and spinal cord to receive and direct information to other organs.
• Reproductive – includes ovaries and testes for reproduction purposes.
• Respiratory – includes the lungs and trachea to take in oxygen and transfer it into the blood stream.
• Skeletal – includes the bones and joints to protect vital organs and support all organ systems.
• Integumentary – includes the skin, hair and nails to protect all other organs from attack by germs and viruses. Helps the body to minimize water loss.
• Immune – includes highly specialized cells that work together to clear infection from the body.

The Integumentary System and The Immune System

Integumentary originates from the Latin word, Integumentum, meaning to cover or enclose. Comprised of skin, hair, nails, and associated glands; the Integumentary System enwraps the body, protecting it from harmful substances entering, while also keeping the necessary nutrients and moisture in.

The Immune System is made up of special cells, proteins, tissues, and organs, which work in synergy to respond to dangerous organisms such as viruses, bacteria and pathogens.

Skin Immunity – Innate and Adaptive

As the largest organ of the body, the skin also represents the largest organ of the immune system.  When our immunity is working at optimum levels, the body has a biological defense that wards off infection, diseases and other unwanted invasions. When assaulted, the skin is flooded with a complex of peptides including Cytokines and Growth Factors.  Functioning as messenger molecules, Cytokines and Growth Factors stimulate cellular proliferation, to repair and restore normal skin function.

There are two types of immune responses generated within the skin, these are innate and adaptive.

Innate Immunity and Keratinocytes:

• Innate Immunity, also known as natural immunity is a type of protection that humans are born with. Considered the first line of defense, innate immunity also consists of certain cells; these non-specifically react on a certain aggressor. Innate immunity includes the external barriers of the body such as the skin, and mucous membranes, like those of the nose, throat and gastrointestinal tract.
• ¹ The innate immune response represents a primitive, but quite effective reaction, which acts in a rapid but nonspecific way. It recognizes the aggressor it may not recognize it. Thus, in contrast to the adaptive response, it is characterized by the lack of immunological memory.  Essential components of the innate response in the skin are cytokines, complement, and recently discovered, antimicrobial peptides. These are not in the skin normally, but when the attack happens, they can be produced by Keratinocytes.
• Keratinocytes are structurally distinct with varying combinations of proteins. They perform numerous immunologic tasks, many of which are still being discovered.  The keratin layer creates an effective barrier to prevent foreign matter from entering while maintaining structural lipids in the skin, minimizing moisturizer loss.
• The Keratinocyte is representative of innate immunity. ² In the last decade it has been discovered that Keratinocytes express Toll-like receptors, (TLR), potent sources of Cytokines, Chemokines and Antimicrobial Peptides.  It has become clear that Keratinocytes may be more than active participants in epidermal immune responses; they may actually play a key initiating role.
• Keratinocytes present the antigen and they produce their own cytokines, which are involved in encouraging immune response. They may also be involved in encouraging epidermal growth factors and fibroblast growth factors.

Adaptive Immunity and Langerhans Cells

• Adaptive Immunity is a second line of protection that builds throughout our lives. Also known as active immunity, it involves the lymphocytes, and develops as we are exposed to diseases or immunized against diseases through vaccination.
• ³ The adaptive immune response is characterized by its specificity, and by the fact that it becomes more effective with each successive encounter with the same antigen (this means it has memory). Crucial components of an adaptive immune response are antigen (aggressor) presenting cells.  In the epidermis, Langerhans Cells are the relevant aggressor cell.
• Langerhans Cells abundant in the epidermis.  They are Dendritic Cells (DC) with octopus-like arms that break up the invading micro-organisms and antigens (agressors).  Their main function is to recognize antigen material and present it on the surface to other cells of the immunity system.  Langerhans Cells are responsible for presenting antigens to T-Cells, which secrete Cytokines.

Histological Changes in Aging Skin

As we age our epidermal immune response diminishes.  Langerhans Cells are diminished; Keratinocytes lose their ability to release Cytokines, cellular proliferation declines and the dermal layer atrophies, causing a loss in resiliency.

The skin is a major force of the body’s immune system.  Arming immuno-compromised skin requires a 3-pronged, inclusive approach to renew and protect the skin topically, nourish the skin internally, and reduce the effects of stress through lifestyle modifications.

Fortunately, the skin’s immunity can be bolstered and through scientific research, I have discovered a new peptide that is independently proven to encourage an immune response.

The Research Behind the Immune Boosting Peptide

In a recent investigative study, working with scientists at the Scientific Center of State Research in St. Petersburg, Russia, I set out to first evaluate the immune-stimulating properties of a newly discovered peptide.  This isolated peptide of algae origin was demonstrated to effectively up-regulate the activity of growth factors in healthy tissues and cell cultures.  The gene of this peptide was cloned, the producer strain was created, the technology of extraction and purification and control methods were developed, and clinical tests were carried out.  The preparation is called Nonapeptide-78 and it is exclusively used in some of my most recent esthetic formulations.

The Nonapeptide-78 has been tested clinically in three different methods:

Test Method 1: Cell Culture on Keratinocytes

• In invitro cell cultures the Nonapeptide-78 was shown to cause the increase in Keratinocyte and epidermal growth factors. 

• In a second invitro test, the Nonapeptide-78 was shown to increase the expression of the genes of fibroblast, epidermal and endothelium growth factors in mononuclears extracted from the peripheral human blood.  Correspondingly, fibroblast, epidermal and endothelium growth factors increased.  Interleukins 6 and 8 were increased in cultures with the Nonapeptide-78 versus the control showing no increase in IL6 or IL 8 in the absence of Nonapeptide-78.

• In skin biopsies taken after 4-6 hours after the application of Nonapeptide-78 the gene expression of Keratinocyte, epidermal growth factor and the basic form of fibroblast growth factors were increased versus the untreated skin in the same panelist.

Preliminary research shows Nonapeptide-78 stimulates the proliferation of genes and growth factor genes.  Nonapeptide-78 sequences the growth factors in cultures to stimulate the proper stem cells to fission and to differentiate into skin cells, fibroblasts and Keratinocytes.  Fibroblasts are responsible for synthesis of elastin, glycosaminoglycans, and the synthesis of collagen. 

Young skin readily regenerates collagen, elastin and glycosaminoglycans.  In aging skin, the quantity of active fibroblasts is greatly reduced which means that synthesis of collagen and elastin decreases. By utilizing the benefits of this new peptide technology, we can stimulate cells to increase the rate of skin cell regeneration and restores skin’s ability to regenerate faster.

Recap

Aging can be characterized by a decline in an individual’s ability to respond and defend itself against stress, environmental damage or internal disorders.  It is well documented that the immune function of humans and other animals declines dramatically during the aging process, increasing the incidence of immune associated diseases.
 
Advances in biotechnology have presented the therapeutic properties of sequenced peptides that show immense promise in enhancing cutaneous immunity, while increasing specific growth factors responsible for Keratinocyte and Fibroblast activity. 

When these advancements are utilized in topical applications, nutritional elements and lifestyle programs, the skincare professional is truly practicing the next generation of skin health.

To learn more about skin immunity, these reference articles provide a depth of knowledge.  In addition, you can inquire about advanced skin immunity seminars through our senior medical education team at 1-800-33-MURAD.
Additional Reading Materials:

• The Nuero-Immuno-Cutaneous-Endocrine Network (N.I.C.E.): Relationship of Mind and Skin, Archives of Dermatology / Volume 134, Nov. 1998.
• Innate Immunity in the Skin:  How Keratinocytes Fight Against Pathogens, Current Immunology Reviews, 2005 / 1
• Skin Immunity, British Journal of Dermatology 2003 /  149
• Who is really under control with skin immunity under physiological circumstances, Experimental Dermatology, 2006 / 1