With a surface area of about 16 to 22 square feet, skin is far more than merely a protective barrier. Your skin is an organ, and it serves to regulate excretion of metabolic waste products, regulates temperature, and includes receptors for pain, tactile sensation, and pressure. Accordingly, the health and appearance of your skin, like the health of your other organs, correlates with the lifestyle and dietary habits that you choose, as well as with critical age-related factors such as hormonal imbalance.
Skin is central in the social and visual experience, as it clearly reflects the consequences of aging. Skin aging is influenced by many factors including ultraviolet radiation, excess alcohol consumption, tobacco abuse, and environmental pollution (Pontius 2011). In addition, few people realize that as their body weight increases and their blood sugar levels rise, biochemical reactions disrupt the very structural framework of their skin. Combined, these factors lead to cumulative deterioration in skin appearance and function.
Within the skin, aging is associated with a loss of fibrous tissue, slower rate of cellular renewal, and a reduced vascular and glandular network. Barrier function that maintains cellular hydration also becomes impaired. The subcutaneous tissue (hypodermis) flattens, particularly in the face, hands and feet.
Depending upon ones genetic makeup and lifestyle, normal physiological functions within the skin may decline by 50% by middle age (Tabor 2009; Fenske 1986).
Unless you take action to support your skin's intrinsic defense systems, the youthful qualities of your skin will rapidly deteriorate. Fortunately, by harnessing insights garnered through the latest scientific innovations, you can dramatically slow, and potentially reverse, the signs and symptoms of accelerated skin aging.
Throughout this Life Extension protocol, you will learn about internal and external strategies to combat accelerated skin aging, including topical interventions containing scientifically advanced ingredients that help support youthful skin structure and function, and targeted nutritional supplements that fortify your skin form the inside out.
Skin Anatomy and Function
In its entirety, the skin is comprised of three distinctive layers, the epidermis, the dermis and hypodermis. Each layer exhibits unique cellular makeup and physiological function.
The epidermis (outer-most layer) is comprised of keratin, which strengthens the skin, and melanin, found in the basal layer of the epidermis, responsible for depth of skin color. Important cellular components in immune recognition of pathogens, called Langerhans cells, also reside in the epidermis. The epidermis provides protection against the environment; the stratum corneum being the primary barrier.
The dermis is directly below the epidermis and provides a kind of scaffold for strength and support. Unlike the epidermis, the dermis contains nerves, blood vessels and fibroblasts that provide sensory receptors, deliver nutrients, and maintain the structural foundation of the skin. The most abundant connective material within the dermis is collagen, a fiberous protein whose primary function is to maintain skin firmness. Elastin protein fibers combine with collagen to give the skin elasticity. The base of the dermis is composed of substances such as complex sugars (glycosaminoglycans), glycoproteins, hyaluronic acid, and chondroitin sulphate. These substances combined form a "cementing and gelling" base that binds to water molecules, allows nutrients and oxygen into the tissue and protects the dermal structural layer. It is within the dermis that new cells are produced and eventually migrate toward the outer layers (the epidermis).
The bottom layer of the skin is the hypodermis. It contains adipocytes (fat cells) that insulate the body and help to preserve heat, as well as other connective tissues.
Skin contains the sebaceous glands and sweat glands (eccrine and apocrine), which help to prevent dryness, protect skin against bacteria, and maintain core body temperature (thermoregulation).
Skin Aging – Contributing Factors
Premature skin aging is the result of several factors such as intense physical and psychological stress, alcohol intake, poor nutrition, overeating, environmental pollution, and UV exposure.
Intrinsic Factors in Skin Aging
Intrinsic skin aging is determined primarily by genetic factors, hormonal status and metabolic reactions, such as oxidative stress. Skin is at risk for similar degenerative effects seen in other organs, yet due to its visibility, the skin outwardly discloses many aspects of our inner health.
Cellular agingis the process by which a cell becomes old and can no longer replicate. Known as "replicative senescence", this phenomenon can be the result of DNA damage induced by factors such as UV radiation, toxins, or age-related deterioration. A hallmark of replicative senescence is the shortening of telomeres, the "caps" at the ends of DNA strands that help ensure chromosomal stability (Buckingham 2011; Attia 2010; Gao 2010).
Skin cells are some of the most rapidly dividing cells in the body. However, as DNA damage accumulates with age, the rapid replication of skin cells causes them to be intrinsically vulnerable to replicative senescence, especially if efforts to protect skin cells from damage are not taken. (Blagoev 2010; Buckingham 2011; Gilchrest 2009).
With aging, there is a decline in the level of sex hormones (estrogen, testosterone, dehydroepiandrosterone sulfate), and growth hormone (Chahal 2007; Makrantonaki 2010). These particular hormones have great influence on the skin. Balance is critical in the realm of hormones, and while escalating sex hormones during puberty increase the incidence of skin acne, declining hormonal levels with aging accelerate skin deterioration (Makrantonaki 2009).
For women, the change in hormone levels, estrogen in particular, during menopause is accompanied by significant changes within the skin. (Verdier-Sevrain 2007). Estrogens influence skin thickness, wrinkling, and moisture (Hall 2004; Phillips 2001; Kanda 2005). Estrogen binds to receptors on skin cells, activating gene expression that modulates skin cell renewal (Ramos-e-Silva 2007; Verdier-Sevrain 2007). With declining estrogen levels, skin cellular renewal becomes sluggish, resulting in thinning of the epidermal and dermal layers. Capillary blood circulation velocity decreases significantly (Raine-Fenning 2003) and the ability for the skin to maintain hydration, strength and elasticity suffers as a result (Verdier-Sevrain, 2007).
As the outermost barrier separating internal tissue from the environment, the skin is regularly exposed to UV radiation and air pollution. These exposures induce the production of highly volatile molecules called free radicals, which go on to wreak havoc in the cellular environment of the skin. Chronic free radical assault leads to the appearance of uneven, blotchy pigmentation, and subverts the structural framework of the skin, giving rise to wrinkles and sagging skin (Fisher 2009). Free radicals also arise from internal, metabolic reactions like glycation from elevated blood sugar,, so simply avoiding exposure to UV light is not adequate for optimal protection.
Oxidative stress plays a central role in initiating and driving events that cause skin aging at the cellular level (Masaki 2010). Oxidative stress breaks down protein (collagen), alters cellular renewal cycles, damages DNA, and promotes the release of pro-inflammatory mediators (cytokines), which trigger the generation of inflammatory skin diseases. It is also established that free radicals participate in the pathogenesis of allergic reactions in the skin (Burke 2009; Fisher 2009; Pascucci 2010; Massaki 2010; Rock 2011).
In addition to the skin's antioxidant defense, epidermal immune cells called Langerhans cells help protect the skin by recognizing antigens (foreign substances) and inducing antibody defense responses. As observed in aging skin there is a reduced number of immune Langerhans cells, thereby affecting skin's ability to ward off stressors or infection that may impact its health (Tabor 2009; Ogden 2011). This is critical, because with advancing age, skin immunity declines, increasing the incidence of infection, malignancies and structural deterioration (skin aging) (Tabor 2009; Ogden 2011).
Elevated Blood Sugar Levels and Glycation
While external factors such as sun exposure can accelerate extrinsic skin aging, scientific evidence points to another culprit: glucose-driven intrinsic aging. Glucose is a vital cellular fuel. However, based on the accelerated rate of aging seen in diabetics, chronic glucose exposure has long been known to affect how the body ages by a process called glycation (van Boekel 1991).
The same browning reaction that occurs when you cook meat at high heat takes place at a slower rate to long-lived tissue proteins such as collagen in our bodies (Dyer 1993). When the proteins in meat are exposed to heat and carbohydrates in the absence of moisture, they cause it to turn brown in a chemical process called the Maillard reaction. Similarly, in the human body, once sugars enter the circulation, they attach themselves to the amino groups of tissue proteins such as collagen to slowly rearrange their youthful structure into the main culprits of damage, called advanced glycation end products (AGEs). AGE molecules are particularly destructive since they can undergo extensive cross-linking with other proteins to form strong chemical bridges. As a result, once healthy collagen fibers lose their elasticity, becoming rigid, more brittle, and prone to breakage (Pageon 2008). Strong scientific evidence also indicates that glycation reactions are promoted by oxidative stress and lead to the production of reactive oxygen species in the skin (Kikuchi 2003).
This assault on the skin's structural support system contributes to the aging of tissues and, when accelerated by hyperglycemia, to the gradual development of diabetic complications. Not surprisingly, collagen abnormalities with aging and in diabetes share similar roots and have widespread consequences for the skin, such as thinning, discoloration, loss of elasticity, and tendency to rashes and infections.
Laboratory research shows that once formed, AGEs can be self-perpetuating—directly inducing the cross-linking of collagen even in the absence of glucose (Sajithlal 1998). Glycation also induces fibroblast apoptosis (cell death), which creates a state of cellular senescence that has been shown to switch fibroblasts from a matrix-producing to a matrix-degrading state (Alikhani 2005). In this state, the secretion of collagen-degrading enzymes, called matrix metalloproteinases (MMPs), increases and levels of their inhibitors decline (West 1994).
In fact, glycation directly increases the release of MMP-1, which preferentially breaks down collagen (Pageon 2007). While these assaults on the skin occur internally, external sources of oxidative stress can also aggravate skin aging. In particular, sun exposure increases levels of MMP-1 in the skin (Fisher 2002).
Extrinsic Factors in Premature Skin Aging
UV Radiation and "Photoaging"
The intrinsic ageing of the skin is exacerbated by environmental (extrinsic) factors. One of the most important extrinsic factors in accelerated skin ageing is solar ultraviolet radiation (UVR). Epidemiological and clinical studies have identified excessive sun exposure as a primary causal factor in various skin diseases including, premature aging, inflammatory conditions, melanoma and non-melanoma skin cancers (Chang 2010; Schmitt 2011).
A series of deleterious biochemical reactions occur within the skin when it is exposed to excess UV radiation; this process is referred to as photoaging.
Chronic sun exposure damages the dermal connective tissue and alters normal skin metabolism. In addition to depressing immunity, and stimulating oxidative stress and inflammation, UV radiation increases the production of matrix metalloproteinases (MMPS), enzymes that degrade collagen (Taihao 2009). The destruction of collagen is a major contributor to the loss of skin suppleness and structure that occurs with advancing age.
The major targets of UV irradiation in the skin are the surface epidermal layers; this results in the depletion of antioxidants such as alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C), which decreases the overall antioxidant capacity within the skin (Masaki 2010). Secondarily to the depletion of vital antioxidant molecules in the epidermis, intrinsic antioxidant defense systems begin to fail; these include superoxide dismutase, catalase, and glutathione-S-transferase (Kregel 2007).
Tobacco use is a major factor that contributes to many chronic diseases and reduced life expectancy (Kim 2010; Nicita-Mauro 2010). Studies have confirmed that smoking tobacco damages the skin via multiple mechanisms as well (Serri 2010).
On the molecular level, tobacco smoke produces oxidative stress, impairs circulation, and triggers DNA damaging reactions, making the skin more vulnerable to disease and aging (Serri 2010; Morita 2009). Visually, "smokers skin" is characterized by increased lines and wrinkles, uneven tone, dehydration, dull and frail skin. Interestingly, smokers who quit have noted dramatic improvements in the visual appeal of their skin, and a more youthful skin appearance has been observed within nine months post-smoking cessation (Serri 2010).
In addition to UV radiation and smoking, pollution is a factor in premature skin aging (Vierkötter 2010). Epidemiological studies have correlated pollution levels with poor health status. Specifically, recent studies relate particle pollution to advanced skin aging. Most notably, skin hyperpigmentation and sluggish skin cell renewal has been observed in both human and animal studies (Pedata 2011; Vierkötter 2010). Individuals concerned with maintaining youthful skin as they age should also review Life Extension's protocol for Metabolic Detoxification, as the information therein can be utilized to help dampen the consequences of environmental toxin exposure.
Combating Skin Aging
Dietary Strategies to Promote Youthful Skin Appearance
As skin is the "visual" organ, the beauty industry's primary objective is to improve the appearance of skin with sophisticated topical treatments and interventions. However, often overlooked is the need support the health and beauty of skin from within through proper nutrition (Buckingham 2011).
In addition to the well-documented role of a wholesome, plant-based diet in maintaining the youthful vivacity of the skin, modern nutritional science is elucidating the relationship between specific nutrients and optimal skin health.
Sadly, the typical North American diet falls considerably short of providing the nutritional composition needed to keep skin healthy and vibrant.
- Macronutrient Composition and Glycemic Load - The North American diet contains excessive amounts of simple carbohydrates and saturated fats. Not surprisingly, this dietary pattern correlates with an increased appearance of skin wrinkles (Cosgrove 2007; Epstein 2010; Nagata 2010; Piccardi 2009).
The glycemic index measures how rapidly and significantly foods cause blood sugar elevations following consumption. Epidemiology data suggest that a high glycemic diet may contribute to inflammatory skin conditions such as acne, rosacea, psoriasis, and eczema as well (Smith, 2008; Veith 2011; Cosgrove 2007).
Insulin resistance and inflammation disrupt sebum production, cause collagen malformation, and excite the epidermal growth factor receptor, which is involved in tissue renewal, but can also stimulate inflammatory reactions in the skin cells (Cosgrove 2007; Epstein 2010; Nagata 2010; Piccardi 2009).
When sugar comes in contact with collagen (a protein), a devastating reaction, called glycation, occurs resulting in the formation of tissue-destroying advanced glycation end products (AGES,) (Danby, 2010). Glycation occurs in all tissues of the body, but is accelerated by a high sugar diet and, within the skin, excessive sun exposure (Avery 2006; Danby 2010; Pageon 2010).
Protein glycation and AGE formation are accompanied by increased free radical activity in skin collagen, which accelerates skin aging (Lyons 1991). All of these changes create an environment within the skin that favors degradation of collagen, compromising the integrity and regeneration of skin tissue.
- Fatty acid composition – Within the skin, fatty acids make up an integral component of cell walls (membranes) that help maintain cell structure and function. Clincial studies show that the healthy balance of fatty acids in skin dramatically decreases with aging and increased oxidative stress, such as that caused by chronic sun exposure (Hayashi 2003; Kim 2010). Therefore obtaining the right amount (and type) of fats through diet or supplementation is critical to maintain healthy skin as we age (Hayaski 2003; Kim 2010; Taylor 2011; Koku 2011). Traditional and non-Westernized diets offer a more balanced intake of omega-6 to omega-3 fatty acids (typically at a ratio of about 4:1) (Taylor 2011; Simopoulos 2011). Today, the North American diet provides a ratio of about 15:1 or more of omega-6's to omega-3's (Simopoulos 2011; Wertz, 2010). Excessive amounts of the omega-6 fat arachidonic acid, found in relatively high quantities in egg yolks, poultry skin, and organ meats from animals fed corn-based diets have a pro-inflammatory effect in the body (including the skin). Conversely, fish oil rich in the omega-3 oils eicosapentaenoic and docosahexaenoic acids (EPA and DHA) inhibit the production of inflammatory metabolites. Due to their ability to modulate inflammation, long-chain omega-3 fatty acids are effective in the management of inflammatory skin conditions, such as acne, psoriasis, eczema, and rosacea. (Taylor 2011; Koku 2011).
- Micronutrient & Antioxidant density - For some time, nutrition experts have recommended choosing whole foods that are micronutrient- and antioxidant-dense over commercially-manufactured, overly processed foods negligible in micronutrients yet rich in fat and carbohydrate calories. This is a critical consideration for skin health as well.
Clinical studies have shown that catechins from green tea, anthocyanins from dark berries and red cabbage, bioflavonoids from citrus, carotenoids such as lycopene and lutein from tomatoes, reservratrol from red wine and genistein from soy offer potent secondary antioxidant protection in the skin (Fortes 2008; Nicols 2010). By including these types of foods more often in the diet, the antioxidant defenses in the skin can be optimized.
- Sodium and Hypertension – The North American diet relies heavily on over-processed, salty foods and some studies suggest that high sodium intake increases the risk of developing hypertension (Dickinson 2006; Dumier 2009). Studies have shown that those with borderline and established hypertension have significantly lower skin capillary densities than non-hypertensive subjects (Tarek 1999). A recent trial proved that by reducing sodium intake in hypertensive subjects, even modestly, microcirculation and capillary densities in the skin can be improved (He 2010).
- Caloric Intake – Data indicate that calorie restriction (CR) promotes longevity through improving body composition and optimizing metabolic function (Teng 2011). Caloric restriction may promote healthier skin aging due to improved skin cell renewal and repair mechanisms as well (Bhattacharyya TK, 2011). Those interested in reading about the numerous benefits associated with caloric restriction should review Life Extension's Caloric Restriction protocol.
Is There and Optimal Diet for Skin Health?
Studies indicate that the Mediterranean diet is linked with improved health and longevity. The Mediterranean dietary pattern centers upon fruits, vegetables, whole grains, legumes, monounsaturated fats (MUFA; like those found in olive oil), and a healthy ratio of omega-3 to omega-6 polyunsaturated fatty acids (PUFAs).
An impressive amount of epidemiological data link the Mediterranean diet with improved cardiovascular, cognitive, and metabolic health (Episoto 2010, 2011; Galland 2010; Nordaman 2011; Kastorini 2011).
The unique properties of this diet are also of particular interest for the skin. The Mediterranean diet may exert an anti-inflammatory effect due in part to its emphasis on extra virgin olive oil, which is high in compounds that modulate oxidative stress and quell inflammatory reactions. A particularly interesting olive oil compound is oleocanthal. This compound has been recently been shown to possess anti-inflammatory actions similar to ibuprofen (Galland 2010; Lucas 2011). In one hospital-based study in Italy, researchers gathered and compared medical and lifestyle history, as well as sun exposure habits and dietary patterns from over 300 controls to over 300 cases of cutaneous melanoma patients. Upon analysis and careful control for sun exposure and pigmentary characteristics, shellfish, fish rich in omega 3 fatty acids, regular tea drinking, and greater consumption of fruits and vegetables were associated with improved skin health (Fortes 2008).
Medical Procedures and Modalities To Combat Skin Aging
As the quest for youth and beauty continues to evolve, research advancements within the cosmetic and medical aesthetics industry have seen exponential growth over the last 20 years (Sachs 2011). Within corrective dermatology, the most sought after treatments include those with the least amount of down time and minimal risk. These include lasers, intense pulsed light, hyaluronic acid based fillers, botulinum toxin (BOTOX®), chemical peeling, radiofrequency, and dermabrasion procedures (Lipozencic 2010).
Medically supervised treatments such as exfoliation-type (microdermabrasion) or chemical peels have been performed for years to rejuvenate the skin. Glycolic acid chemical peels offer a non-invasive treatment to help renew skin surface. After application, the peel lifts off the surface layer of the skin to bring out a radiant glow and minimize visibility of fine lines and wrinkles. Although chemical peels are used mostly on the face, they can also be used to improve the skin on the neck and hands (Briden, 2004).
With advanced technology there are now a multitude of devices and mechanisms available to thermally treat the skin. These include laser or intense pulsed light (IPL) skin resurfacing and may require a mild anesthetic and short recovery period. To date, fractional laser resurfacing have become popular in medical aesthetic practices as they have exhibited favorable outcomes with minimal recovery time. In general, this type of treatment involves the application of a focused laser light to the skin. With the heat generated by the light, upper and middle layers of skin are removed. After skin healing, general results show a visible improvement in skin coloration and softening of fines lines and wrinkles (Brightman 2009; Lipozencic 2010).
To help restore volume, smooth skin appearance and minimize fine lines and wrinkles, semi-permanent (BOTOX®, Juvederm®), and more permanent dermal fillers (Restylane®) are treated to the eye area, forehead and nasolabial folds (smile lines). The procedure occurs with a local injection to the treated area of the face. Depending upon the type of filler used, results generally last from 3 to 4 months (BOTOX®,) 6 months to a year (Juvederm®), or up to 3 years Restylane®) (Sturm 2011).
In the last few years, skin cell regenerating creams have been brought to market in the hope to combat the signs of skin aging. Of particular interest is stem cell therapy. Adult stem cells are found in different tissues, such as the brain, bone marrow, blood vessels, muscle and skin. They generally will remain inactive until they are activated by injury or for example, chronic photodamage to the skin. Once activated, stem cells can regenerate a range of cell types from the originating organ. In skin, stem cells that lie just beneath the surface have been used to engineer new skin tissue that can be grafted on to burn victims (Lataillade 2010.)
One of the most recent treatments in stem therapy include the use of adipose-derived stem cells (ADSC,) which have been shown to in animal studies to combat free radical damage and age spots, and promote wound healing in the skin upon injection (Kim 2011; Zhong 2011). Experiments suggest that ADSC's, when injected subcutaneously, stimulate collagen synthesis and the formation of new blood vessels (angiogenesis) (Kim 2011). These findings indicate that ADSC's may be an effective anti-aging strategy for maintaining skin vitality.
Hormone Therapy and Skin Aging
As outlined earlier in this protocol, age-related changes in hormone levels, especially that which occurs during the menopausal years for women, have dramatic effects on skin health. Therefore, utilizing natural bioidentical hormone replacement therapy as a means to maintain hormones in a youthful range is a provocative strategy for combatting skin aging. Indeed, several trials have shown that hormone replacement therapy improves skin quality.
To assess the effects of estrogen replacement therapy on skin aging, 40 post-menopausal women received systemic estrogen replacement therapy for seven, 28-day cycles. By the end of the trial, skin elasticity and hydration improved significantly, with no adverse effects reported (Sator 2007).
In another trial, researchers aimed to assess the effects of systemic estrogen therapy on skin collagen in post-menopausal women. Researchers found that, by 16 weeks of treatment, collagen content had significantly increased in facial skin, resulting in improved texture and firmness (Patriarca 2007). There are also some studies that have noted visual improvements in skin dispigmentation (age spots) and wrinkle reduction in peri- and post-menopausal women treated with systemic transdermal estradiol-based creams (Creidi 1994; Dunn 1997; Sator 2007).
DHEA and Melatonin
The sleep hormone (melatonin) and the anti-stress hormone (DHEA) are both found in human skin. Both are converted into entities with biological roles within the skin. DHEA is converted into estrogen- and androgen-type metabolites unique to the skin (Labrie 2000). Melatonin is synthesized in skin. In low concentrations it can stimulate cell growth. This type of on-site, organ-specific production of hormones is called intracrine biosynthesis. Intracrine biosynthesis allows different organs to manufacture the substances they need without flooding the entire body with growth factors.
Although the exact roles of DHEA and melatonin in human skin are still under scrutiny, researchers have identified several mechanisms through which these hormones protect against aging, maintain the health of skin, and affect how sunlight reacts with skin cells.
DHEA has beneficial effects beyond its conversion to skin-friendly hormones. DHEA itself has powerful skin protective effects. A study in the Journal of Surgical Research demonstrates the extraordinary ability of topically applied DHEA to protect skin's delicate blood vessels. Researchers found that if DHEA was applied after a serious burn, the blood vessels underlying the burned area are protected (Araneo 1995). DHEA also has antioxidant action against peroxyl and superoxide free radicals, and also limits the bioactivation of some toxins (Schwartz 1986a; Schwartz 1986b; Hastings 1988). DHEA blunts chemical carcinogen-induced DNA damage as well (Pashko 1985; Pashko 1991).
A 2008 clinical trial found that topical DHEA improved skin brightness and texture in postmenopausal women after four months of treatment (Nouveau 2008).
Melatonin is an antioxidant hormone that protects against UV radiation (Fischer 1999). A group at the University of Zurich has shown that topical melatonin gives excellent protection against sunburn if applied before sun exposure (Bangha 1997). Melatonin may be involved in repairing burned skin as well (Scott 1986). Moreover, melatonin appears to play a role in regulating blood circulation within the skin as well (Aoki 2008).
An animal model of pressure-ulceration revealed that melatonin, both topically and systemically, ameliorated disruption in antioxidant defense system within the skin (Sener 2006).