Improving Wound Healing & Aging Skin With Small Molecule Skin Nutrition

It’s estimated that annual wound care costs in the United States exceed $15 billion for the aging population,¹ making improvements in wound care for this patient population a healthcare priority. The proportion of aging individuals among the general population is increasing dramatically, with the number of adults aged 65 years or older projected to almost double (from 35 million to 53 million) by the year 2030.² As individuals live longer, there is an urgent need for optimal care of aging skin that is increasingly recognized.³ This article will discuss the challenges that healthcare providers face when helping older patients manage their skin care and offer strategies for treating aging skin in the outpatient wound care clinic at the time of patient discharge to home.

AGING SKIN: HOW DOES IT HAPPEN?

Two types of skin aging exist — intrinsic and extrinsic aging — and they typically overlap. Intrinsic aging occurs naturally and is affected by normal human factors such as individual genetics and changes in cell signaling, whereas extrinsic aging occurs due to environmental stressors such as ultraviolet radiation (UVR), pollution, and smoking. Skin that is extrinsically aged by UVR (ie, photoaged) is “leathery” in appearance with decreased elasticity, deep wrinkles, uneven pigmentation, and rough texture. Intrinsically aged skin is transparent and characterized by fine wrinkles. Loss of pigment and skin pallor is due to decreased numbers of pigment-producing melanocytes and decreased vascularity in aged skin, which results in decreased sun protection and fewer nutrients accessing the skin from circulating blood, respectively.^4-6 Aging skin becomes more fragile and loses 20% of its thickness⁷ (Figure 1). As skin ages, it becomes more permeable and susceptible to irritation, and the skin barrier decreases³ (Figure 2). Skin irritation often results in inflammation that can lead to itching, wounding, and infections. Small molecule topical nutrition can penetrate the epidermis to strengthen, soothe, hydrate, and protect skin.⁸ Topical small molecule technology (found in AtHome^™ Viniferamine^® skin and wound care products [McCord Research, Coralville, IA]) has been used to deliver nutrients to skin and improve wound healing outcomes.⁹

SKIN BRUISING & TEARS

A flattening of the junction between the epidermis and dermis is also found in aging skin that is due to a loss in rete ridges, the epithelial extensions that project into the underlying connective tissue in both skin and mucous membranes (Figure 3). The resultant loss of corrugation at the junction of these skin layers corresponds with less skin resistance against shearing forces and greater susceptibility to skin tears. Decreased vascularity in aging dermis is due in large part to the loss of capillary loops associated with the rete ridges.⁴ In addition, there is a decrease in subcutaneous fat tissue that would normally cushion the skin and blood vessels, rendering the skin more susceptible to bruising,⁶ which is often associated with skin tears.¹⁰ The AtHome Viniferamine Fragile Skin Bruising Care kit can help aging patients avoid skin bruising and skin tears through the use of a nourishing moisturizer and a gentle cleanser that protect and strengthen aging skin while preventing skin irritation that can lead to wounding. Several ingredients found in Viniferamine products also increase and strengthen the skin barrier. Quantitating transepidermal water loss (TEWL) is a way to assess the quality of the skin barrier and how well it functions. Oleuropein, a potent small molecule polyphenol found in olives, has been shown to reduce TEWL, indicating its ability to increase skin barrier function.¹¹ Evidence also demonstrates that melatonin has a stimulatory role in building and maintaining the epidermal barrier.¹² In addition, niacinamide has a stabilizing effect on the epidermal barrier, as evidenced by a reduction in TEWL following topical application.¹³ Aging skin becomes drier due to a decrease in skin lipids and sebaceous glands, making aging individuals more susceptible to xerosis (chronic dry skin), which can result in skin inflammation, and irritation, pruritus, and wounding.^14,15 The AtHome Viniferamine Chronic Dry Skin Care kit is designed to decrease xerosis and includes a renewing moisturizer and a mild cleanser. In fact, lipid metabolism in the skin decreases with age, and the enzymes required for ceramide production that is vital for skin barrier function are diminished. Lipids (including ceramides) found in extracellular spaces (between cells) in the epidermis help provide a barrier to moisture and electrolyte loss. Importantly, low ceramide levels are associated with dermatitis; however, niacinamide, which is also found in the Viniferamine products, can help increase the biosynthesis of ceramides and other lipids.^15-17 Other studies have indicated that healthy individuals over the age of 65 frequently have delayed wound healing.^6,18 Various ingredients in the Viniferamine products also enhance wound healing, including oleuropein, which was shown to improve wound healing in an aging model.¹⁹ Resveratrol, a small molecule polyphenol found in grapes, has been shown to improve wound healing in individuals living with type 2 diabetes.²⁰ Epigallocatechin-3-gallate (EGCG), a small molecule polyphenol found in green tea, has been shown to accelerate keratinocyte differentiation and wound healing,²¹ and melatonin was shown to accelerate the process of wound repair in full-thickness incisional wounds.²² In addition, L-carnosine, a dipeptide molecule made up of the amino acids beta-alanine and histidine that is highly concentrated in muscle and brain tissue, stimulated wound healing in an incision wound model.²³ Also, L-glutathione, an important antioxidant that’s capable of preventing damage to important cellular components caused by reactive oxygen species (ROS), was found to be beneficial for ischemic wound healing.²⁴ Moreover, Centella asiatica²⁵ and one of its main components — asiaticoside²⁶ — a triterpene glycoside that has antibiotic properties, have important wound healing activities. Additionally, the skin-conditioning agent dipotassium glycyrrhizate is known to protect hyaluronic acid,²⁷ which also plays a role in wound healing.²⁸ 

ADDRESSING COMORBIDITIES 

Along with delayed wound healing, it is common for individuals older than 65 to experience comorbidities that can lead to impaired wound healing, including peripheral arterial disease (PAD), obesity, and/or cancer^29,30 (Figure 4). In fact, data from the U.S. Wound Registry suggest that patients treated in outpatient wound clinics have an average of six comorbidities, which also frequently include renal failure, diabetes, and malnutrition.³¹ Age-related changes are apparent in all phases of wound repair and the disruption of any step in the wound healing process can lead to a delay in healing by 20-60%.²⁹ Various other factors that are frequently associated with aging can affect wound healing, including the decline of sex hormones, psychological stress, neuropathy, poor hydration, compromised immunity, and increased oxidative stress.^29,30,32-34 Oxidative stress occurs when the production of ROS overwhelms the skin’s natural defense —  including antioxidants and antioxidant defense enzymes such as superoxide dismutase (SOD) — resulting in DNA, protein, and overall cellular damage, as well as inflammation.³⁵ ROS are continuously produced as side products of metabolism in the mitochondria, and keratinocytes and fibroblasts in the skin are the main producers of mitochondrial ROS. During skin aging, the effectiveness of the skin’s natural antioxidant system is diminished and ROS production results in increased degradation of collagen.⁵ In fact, the overall content of collagen over a unit area of skin has been found to decrease approximately 1% per year.³⁶ In an experimental model in which SOD was absent, degeneration of collagen was evident.³⁷ 

Collagen is vital for wound healing since it has a structural role in providing tensile strength to wounds. In addition, collagen modulates critical inflammatory and wound healing processes by binding to receptors that activate other molecules involved in tissue remodeling and repair, including growth factors.^38,39 Nonenzymatically formed crosslinks can form between proteins such as collagen and sugars (known as glycation)⁴⁰ that are increased with oxidative stress and aging.⁴¹ Glycation results in stiffer, more brittle collagen.⁴⁰ In addition, the collagen in aging skin is disorganized. Moreover, fibroblasts that normally produce collagen become senescent (lose the ability to replicate) with aging, leading to increased inflammation and the production of matrix metalloproteinases that degrade collagen.⁵ Some of the ingredients found in the Viniferamine products help increase collagen, including titrated extract of C. asiatica (TECA) and aloe vera that stimulate collagen synthesis and enhance wound healing.^25,42,43 Immune cells in the skin and elsewhere, including macrophages, can also become senescent, leading to immunosenescence and immune dysregulation that can result in impaired wound healing.⁴⁴ Oxidative stress is an important cause of cellular senescence.³³ Viniferamine products also include various nutrients that counteract oxidative stress, including the important small molecules oleuropein, resveratrol, and EGCG, as well as L-carnosine, melatonin, and L-glutathione.^24,45-48 Interestingly, in a model where manganese (Mn)SOD was deactivated, oleuropein induced MnSOD activity,⁴⁹ EGCG was found to induce MnSOD expression,⁵⁰ and resveratrol was shown to upregulate MnSOD activity.⁵¹ Another important factor that affects wound healing in the aging population is an increased likelihood of polypharmacy due in part to comorbidities.³⁰ In fact, certain medications can interfere with wound healing. These include systemic glucocorticoid steroids (including those used in treating rheumatoid arthritis) and chemotherapeutic drugs, as well as anticoagulants, nonsteroidal anti-inflammatory drugs, and pain medications (eg, morphine).^29,30 Systemic glucocorticoids inhibit wound repair by suppressing fibroblast proliferation and collagen synthesis. Chemotherapeutic drugs delay skin cell migration, impair skin cell proliferation, and reduce angiogenesis and extracellular matrix formation.⁵² Aging individuals are also more susceptible to chronic wounds due to comorbidities, decreased immune function, and increased susceptibility to infections.^2,30,31 Individuals aged 65 and older account for most of the expenses associated with annual chronic wound care in the U.S.⁵³ More than one-third of the aging population (older than 65) is obese, which places many at increased risk for diabetes and vascular disease. In fact, approximately, 25% of individuals older than 65 are clinically diabetic³¹ and 20-40% of these patients live with PAD.⁵⁴ Evidence also suggests that diabetes accelerates the aging process.³¹ In addition, approximately 70% of pressure ulcers occur in the aging population.⁵⁵ Many factors can increase the risk for pressure ulcers in this population, including malnutrition, immobility, loss of cognitive abilities, and decreased blood flow, as well as dry skin and skin maceration that makes the skin more vulnerable to damage.^3,55 Therefore, nourishing, strengthening, and moisturizing will help prevent these wounds in aging skin. Macerated skin can also be strengthened and restored with nourishing creams that contain zinc oxide, such as Viniferamine SkinMineralZ.^™

CONCLUSION

Aging skin is more fragile and susceptible to wounding. The aging population is increasing dramatically, and wound care costs for this group are rising rapidly in part due to this population being more likely to become chronic. Understanding the impact that aging can have on skin biology and wound healing can help clinicians adapt their care plans to better address the various physiological manifestations of aging. When initiating a care plan in the wound clinic, it’s essential that a plan is selected that can be continued across all care settings, including at home. Utilizing specialized skin care kits can be an effective method to continue care plans across all settings while utilizing appropriate products that address the underlying issues of aging skin and delayed or impaired wound healing. 

D. Elizabeth McCord, senior researcher at McCord Research, Coralville, IA, is a renowned biochemist in the field of skin and wound care. She has been awarded six patents and two medical devices, and has more than 60 health products marketed globally. She previously commercialized wound and skin care products under the Remedy^® Olivamine^® brand. Kyle D. Hilsabeck is vice president of pharmaceutical affairs at McCord Holdings and licensed by the Iowa Board of Pharmacy. He completed bachelor’s degrees in biology and biochemistry at Wartburg College, and his doctorate at the University of Iowa College of Pharmacy. He completed a community pharmacy residency through the University of Iowa and taught for the University of Iowa College of Pharmacy. Nancy B. Ray is science officer at McCord Research. She currently writes and presents on diabetes, skin care, and other topics to advance skin care and wound healing awareness. She received her PhD in biochemistry and biophysics at Oregon State University and was a postdoctoral fellow at the National Institutes of Health, Harvard University, Dana-Farber Cancer Institute, and the University of Iowa. She also earned bachelor’s degrees in chemistry and microbiology from the University of Montana.