Woman painting her healthy nails

Skin, Hair, and Nail Health

Skin, Hair, and Nail Health

Last Section Update: 07/2023

Contributor(s): Maureen Williams, ND; Robert Iafelice, MS/RD/LDN; Chancellor Faloon, Health & Wellness Author

1 Overview

Summary and Quick Facts for Skin, Hair, and Nail Health

  • The health and appearance of our skin, hair and nails depends on the health of several structural proteins they share, namely collagen, keratin and elastin. Taking steps to keep these proteins healthy is critical.
  • In this protocol you will learn about factors both inside your body and from the external environment that can damage skin, hair and nail proteins. Learn about medical, dietary and lifestyle strategies to support healthy skin, hair and nail proteins.
  • Protecting yourself from environmental factors like too much sun, and internal factors like elevated sugar levels, can help.
  • Supplementation with specialized collagen peptides is one way to help support the collagen protein network that gives skin its supple, youthful appearance.

The appearance and integrity of our skin, hair, and nails are dependent upon a framework of structural proteins, especially keratin, collagen, and elastin.

The problem is intrinsic factors, such as the biological aging process, as well as extrinsic factors, such as ultraviolet radiation from sun exposure, compromise the structure and function of these proteins.

Fortunately, lifestyle changes and targeted nutritional interventions—particularly collagen peptides, solubilized keratin, and Polypodium leucotomos extract—can support skin, hair and nails from the inside out.

Factors That Compromise Skin, Hair, and Nail Health

Intrinsic Factors:

  • Biological aging, which affects collagen, elastin, keratin, melanin and levels of hormones to drive changes in skin, hair, and nail quality.
  • Elevated blood sugar and inflammation, which damage collagen and interfere with its production.

Extrinsic Factors:

  • Ultraviolet (UV) radiation, which causes free radical damage and increases the activity of enzymes that break down collagen and elastin.
  • Smoking and air pollution, both of which damage skin.

Conventional Cosmetic Interventions

  • Minimally invasive methods including chemical peels, dermabrasion or microdermabrasion, botox injections, and laser skin resurfacing.
  • Injectable hyaluronic acid or topical tretinoin (Retin-A) are also commonly used.

Novel and Emerging Strategies

  • Topical estrogens were shown to improve skin elasticity and decrease wrinkle and pore size in a study on premenopausal women.
  • Platelet-rich plasma, derived from the patient’s own blood, significantly improved facial skin’s general appearance, firmness, sagging, and wrinkles.
  • In a survey of radiofrequency treatments, 87% of patients noted immediate skin tightening and 92% reported tightening that lasted six months after treatment.

Diet and Lifestyle Considerations

  • Eat a plant-based, minimally processed, low-sugar diet.
  • Apply sunscreen 30 minutes before going outside—evidence has shown daily use of sunscreen resulted in no noticeable increase in skin aging after 4.5 years.
  • Get adequate sleep, as lack of sleep may negatively impact collagen formation and skin integrity.

Integrative Interventions

  • Collagen peptides: Preclinical and clinical evidence has demonstrated that oral intake of collagen peptides reduces wrinkles and improves skin moisture, elasticity, and may help protect against photoaging.
  • Solubilized keratin: Oral ingestion of solubilized keratin plus vitamins and minerals significantly improved various aspects of skin appearance, decreased hair loss, and increased nail strength.
  • Polypodium leucotomos extract: Accumulating evidence indicates oral supplementation of Polypodium leucotomos extract provides potent protection against skin photoaging, suggesting it may also have a role in skin cancer prevention.
  • Nicotinamide: Treatment with nicotinamide resulted in a 23% lower rate of new non-melanoma skin cancers and an 11‒20% reduction in incidence of the precancerous lesion actinic keratosis compared with the placebo group.
  • Phytoceramides: In a randomized trial, women aged 20‒63 years with dry skin were given either a non-GMO wheat extract containing ceramides or placebo for three months. In the ceramide group, a significant increase in skin hydration and an improvement in clinical signs of dryness were observed at the end of three months.

2 Introduction

Aging causes changes in the structural foundations of skin, hair, and nail tissue. This leads to aesthetic changes such as wrinkled, dry skin; thinning, greying hair; and dull, brittle nails (NLM 2016a; NLM 2016b). Although aging affects the whole body, our skin, hair, and nails provide a window through which the manifestations of aging can be viewed by others. Thus, age-related cosmetic changes are a concern for everyone and can have significant psychosocial implications (Montemurro 2013; Saxon 2010; Gupta 2005).

The appearance and integrity of our skin, hair, and nails are dependent upon a framework of structural proteins, especially keratin, collagen, and elastin (NIH 2016; Giesen 2011; Baud 2013; Kadler 2007; McLafferty 2012).

  • Keratin is a key structural protein in hair, nails, and the outer layer of skin.
  • Collagen fibers are the principle source of skin’s strength.
  • Elastin fibers provide elasticity and resilience to skin.

The problem is that intrinsic factors, such as the biological aging process, as well as extrinsic factors, such as ultraviolet (UV) radiation from sun exposure, compromise the structure and function of these proteins. This causes the appearance and texture of our skin, hair, and nails to deteriorate over time (Kambayashi 2001; Uitto 2008; NIH 2016; Giesen 2011; Calleja-Agius 2013; Baud 2013; Baumann 2007).

At the cellular level, glycation is a major contributor to skin aging. Glycation is the same reaction that causes foods to brown when cooked at high temperatures. In the body and skin, glycation involves the bonding of sugar molecules with proteins and fats. This reaction is markedly accelerated when blood sugar is elevated, as in diabetes (Felipe 2011; Gkogkolou 2012; Singh 2014).

Glycation causes collagen and elastin proteins to change into advanced glycation end products (AGEs), disrupting the skin’s structural framework (Singh 2014; Pageon 2014; Gkogkolou 2012). AGEs also promote chronic inflammation in skin cells, which further contributes to skin aging (Sanguineti 2014; Gkogkolou 2012).

Whether skin aging is caused prematurely by extrinsic factors (eg, sun, smoking, etc.), or develops intrinsically through natural “wear and tear,” the end result is the same: weathered-looking skin characterized by dryness, wrinkling, thinning, discoloration (“age spots”), and decreased elasticity (Michels 2011; Baumann 2007; Calleja-Agius 2007; Calleja-Agius 2013).

Unless you take action to support your skin's inherent 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 premature skin aging.

In this Life Extension protocol, you will learn about strategies to combat internal and external causes of skin, hair, and nail deterioration. These include positive lifestyle habits, particularly healthy eating, regular exercise, using sunscreen, and quality sleep. Topical interventions containing scientifically advanced ingredients that help support youthful skin structure and function will be discussed as well. Finally, you will discover how targeted nutritional interventions—particularly nicotinamide, Polypodium leucotomos, red orange extract, phytoceramides, and omega-3 fatty acids—can fortify your skin from the inside out.

Note: this protocol primarily encompasses hair, skin, and nail general health and aesthetics. Specific skin and nail diseases are covered in other Disease Prevention and Treatment protocols.

3 Factors That Compromise Skin, Hair, And Nail Health

Intrinsic Factors

Several inherent biological variables influence skin, hair, and nail health; these are intrinsic factors (UMMC 2016; Trüeb 2006).

Biological aging. The biological aging process underlies several factors that drive changes in hair, skin, and nail quality (Giesen 2011; Besdine 2016; Makrantonaki 2010; Quan 2010).

  • Collagen, elastin, and keratin are critical structural proteins in the skin, hair, and nails. Production of these proteins decreases with advancing age (Calleja-Agius 2007; Baud 2013; Giesen 2011; Baumann 2007).
  • Diminishing fibroblast stimulation. Fibroblasts produce collagen-rich connective tissue that is central to the structure and function of the skin. Collagen-producing fibroblasts in the skin are dependent on signaling from cytokines called transforming growth factor beta and connective tissue growth factor. Levels of these key growth factors decline with age. This leads to loss of skin collagen and thin, fragile skin (Quan 2010; Dahl 2010).
  • Melanin is the pigment responsible for skin and hair color (Levinbook 2016). The number of melanin-producing cells (melanocytes) decreases at a rate of 8‒20% per decade, resulting in less protection against UV radiation and uneven pigmentation in elderly skin (Besdine 2016; Farage 2013). In hair follicles, gradual loss of melanocytes leads to greying of hair (Ortonne 1990).
  • Cells and tissues that maintain the structure and function of the skin are influenced by hormones (Sator 2004). Aging is associated with a decrease in the level of various hormones including estrogen, testosterone, dehydroepiandrosterone (DHEA), and growth hormone (Makrantonaki 2010; Phillips 2001); this may contribute to skin aging. Note: Information about hormone restoration for both men and women is available in the Male and Female Hormone Restoration protocols; the DHEA Restoration protocol may be helpful as well.

Elevated blood sugar and glycation. Glycation occurs when sugars react with proteins or fats to form advanced glycation end products (AGEs) (Pageon 2010; Gkogkolou 2012). Collagen, the skin’s primary protein, is long-lived, with a slow renewal rate. Consequently, it is thought to be especially prone to glycation-induced damage. The formation of AGEs causes crosslinking (bonding) of collagen fibers to each other. This leads to thinner skin with decreased elasticity, and the development of wrinkles (Pageon 2014; Pageon 2010; Gkogkolou 2012).

Inflammation. Inflammation promotes skin aging by interfering with collagen synthesis and promoting collagen breakdown. Inflammation-stimulated collagen breakdown is partly attributable to collagen-degrading enzymes called matrix metalloproteinases (Borg 2013).

Extrinsic Factors

Environmental influences, such as sun exposure and pollution, also contribute to the degradation of skin, hair, and nail tissue; these are called extrinsic factors.

Ultraviolet (UV) radiation and “photoaging.” While many extrinsic factors play a role in skin aging, UV radiation from the sun is one of the most damaging. Chronic sun exposure is believed to account for as much as 80% of facial skin aging. Permanent damage to the skin from prolonged UV light exposure is termed “photoaging” (Michels 2011; Baumann 2007).

  • Oxidative stress. One mechanism by which UV light ages the skin is through free radical damage. Collagen and elastin fibers in the skin are targets of these destructive molecules (Amaro-Ortiz 2014).
  • Metalloproteinases. Matrix metalloproteinases play a vital role in premature skin aging induced by chronic exposure to UV light. These enzymes break down collagen and elastin fibers, as well as other structural proteins, in photoaged skin. UV radiation increases the expression of several different matrix metalloproteinases in the skin (Quan 2009).

Smoking. Tobacco smoke irreversibly damages the skin and accelerates skin aging. Smoking is also linked to many skin conditions including delayed wound healing, squamous cell carcinoma, melanoma, oral cancer, acne, psoriasis, and hair loss (Urbanska 2012; Morita 2007).

Pollution. In a study in elderly women, exposure to traffic-related air pollution was strongly associated with skin aging, including a 20% increase in pigment spots on the cheeks and forehead, and significantly more pronounced wrinkles (Vierkotter 2010). Individuals concerned with maintaining youthful skin should also review Life Extension's Metabolic Detoxification protocol, as the information it contains can be utilized to help lessen the body’s toxin burden.

4 Conventional Cosmetic Interventions

Although no treatment can entirely reverse the effects of aging, there are a number of treatment options for reducing the evidence of photodamage and other age-related skin changes. All of these therapies carry a risk of side effects, and most require multiple treatments to achieve and maintain results, some at considerable expense. A frank discussion with a healthcare provider about realistic expectations, risks, and costs is necessary before embarking on a course of anti-aging cosmetic therapy (Mayo Clinic 2014).

Chemical Peels

A chemical peel, also called chemexfoliation, is a minimally invasive method to improve the appearance of the skin. The process involves applying a chemical solution to the skin to intentionally cause minor damage and subsequent repair and rejuvenation of the skin surface. The new skin usually has a smoother texture with less wrinkles. Chemical peels can be used on the face, neck, and hands. They can be beneficial in a number of conditions including acne scars, aging skin, crow’s feet, scars, sun damaged skin, and wrinkles (ASPS 2016a; ASDS 2016a).

Different chemical formulations can reach different depths of the skin. Superficial peels can treat minor skin irregularities and shallow wrinkles, while deeper wrinkles and more pronounced irregularities may require deeper-peeling chemical formulations. Chemicals that may be used in chemical peels include alpha-hydroxy acids (such as glycolic and lactic acids), trichloroacetic acid, beta-hydroxy acids, and others (Hassan 2013).

Potential side effects of chemical peels include temporary or permanent change in skin color, scarring, and reactivation of cold sores (ASDS 2016a). Recovery time and potential for adverse effects depends on the strength of the chemical formulation and depth of exfoliation; side effects typically last for several weeks. With milder peels, multiple treatments are typically required before results are seen (Mayo Clinic 2014).

Dermabrasion. Similar to chemical peeling, dermabrasion causes exfoliation of the upper layers of skin, leading to growth of new skin. Dermabrasion uses mechanical or abrasive means to remove the top layers of skin. Skin dermabrasion procedures can be used for general anti-aging rejuvenation or to minimize the appearance of minor scars or other mild-to-moderate abnormalities. Dermabrasion removes the epidermis and penetrates into the dermis.

Because dermabrasion involves the removal of live tissue, it is painful and requires the use of an anesthetic, ranging from topical anesthetics to full sedation, depending on pain sensitivity of the individual and degree of dermabrasion needed. Redness and crusting are typical during the recovery period and may last roughly two to three weeks. Antibiotic, anti-inflammatory, and analgesic ointments for the affected area are often recommended after treatment (Alkhawam 2009). Some dermatologists prescribe topical tretinoin (eg, Retin-A) for a few weeks before dermabrasion, as this may shorten healing time and reduce post-procedure skin abnormalities (Mandy 1986). Sun exposure should be minimized for a month or more before and after dermabrasion. Although uncommon, lasting redness, scarring, or other skin abnormalities may occur (Alkhawam 2009).

Microdermabrasion is similar to dermabrasion but slightly less invasive, removing only the upper layers of the epidermis. Microdermabrasion can minimize appearance of very superficial skin abnormalities or be used to improve general skin appearance (Alkhawam 2009). This gentle technique produces modest, temporary results that may require as many as 16 treatments to be seen (Mayo Clinic 2014). Given that only the upper layers of the epidermis are affected, microdermabrasion is considered a relatively safe technique with minimal redness after treatment; however, in rare cases, prolonged redness, itching, small vessel breakage, bruising, and pinpoint bleeding can occur (Alkhawam 2009; El-Domyati 2016; ASPS 2016c).

Individuals currently undergoing treatment with isotretinoin (Accutane) or who have an active herpes outbreak should consult a healthcare professional before undergoing dermabrasion or microdermabrasion procedures (Alkhawam 2009).


Botox (the brand name for botulinum toxin type A) injection is one of the most popular cosmetic procedures in the Unites States. Numerous studies have demonstrated Botox injections can be a safe and effective treatment for facial wrinkles, including frown lines, crow’s feet, and forehead lines (Hexsel 2011; Small 2014).

Botox is a neurotoxin that inhibits the release of acetylcholine, a neurotransmitter needed for muscle contraction. By injecting very small amounts of Botox at selected sites, a temporary relaxation of facial muscles and reduced appearance of wrinkles can be achieved (Hexsel 2011; Small 2014). The results may last several months, and repeated treatments are needed for maintenance (Mayo Clinic 2014).

Minor bruising and pain at the injection site, as well as allergic reactions, can occur after Botox injections (Hexsel 2011; Small 2014). Other complications include facial asymmetry and lowering or drooping of the eyelid or eyebrow due to migration of the neurotoxin. Although these complications are uncommon and temporary, they are often very distressing when they occur (Small 2014).


Tretinoin (also known as all-trans retinoic acid or, eg, Retin-A) is a pharmaceutical retinoid (vitamin A derivative) approved by the Food and Drug Administration (FDA) for topical use to treat photodamage, acne, and other skin conditions including psoriasis and basal cell carcinoma (Ascenso 2014; Ting 2010; Kligman 1989; CIHR 2016). Tretinoin stimulates new collagen formation and decreases collagen loss, inhibits skin metalloproteinases, increases fibroblast proliferation, and suppresses inflammation (Baldwin 2013; Ascenso 2014; Mukherjee 2006).

Although tretinoin appears to be helpful in treating photoaging of the skin, mild-to-moderate side effects such as skin redness, irritation, burning, and scaling are common (Culp 2015; Mukherjee 2006; Geng 2009). Tretinoin increases sun sensitivity, so topical sunscreens and sun-protective clothing are recommended during treatment to prevent sunburn (Mayo Clinic 2014).

Laser Skin Resurfacing

Laser skin resurfacing can help improve the appearance of wrinkles, blemishes, and scars. Modern laser methods are precise and are considered to be suitable for facial skin (ASPS 2016b; ASDS 2016b). Laser resurfacing is used to treat a range of skin flaws associated with aging and photoaging, including liver spots, vascular lesions such as telangiectasia and rosacea, and fine lines and wrinkles (Lipozencic 2010a; Lipozencic 2010b; ASPS 2016b). A common laser resurfacing procedure is fractional skin resurfacing in which partial, precise, targeted laser application leaves small areas of the normal skin surface intact (Carniol 2015; Lipozencic 2010b; Halbina 2014; Lipozencic 2010a).

After laser therapy, individuals generally experience mild burning, swelling, flaking and peeling, and changes in skin color (bronzing) that can persist for months. These symptoms heal more quickly and the risk of infection and permanent scarring and skin color change is lower with fractional laser therapy compared with other laser resurfacing techniques; however, fractional laser therapy typically requires more treatment sessions (Halbina 2014; Mayo Clinic 2014).

Injectable Hyaluronic Acid

A number of injectable hyaluronic acid preparations are FDA approved to treat characteristic signs of facial aging such as loss of skin volume and elasticity, and appearance of wrinkles and folds. Originally developed in Europe, hyaluronic acid dermal fillers replaced problematic injectable collagen products and have become one of the more popular treatments in the field of cosmetic dermatology. Hyaluronic acid is a naturally occurring substance in many tissues in the body. This compound strongly attracts water molecules, restoring fullness and volume to the skin (Gold 2007; Manna 1999; ASOPRS 2015; FDA 2016; Suman 2011; Edwards 2007).

Among the approved brands of hyaluronic acid injectables are Restylane, Juvederm, Hylaform, Puragen and Captique. Some hyaluronic acid injectable products are derived from animal tissues, while many are created by bacterial synthesis. Effects of hyaluronic acid injection procedures are quickly seen and can last up to six months. The procedure is relatively safe, but can produce redness, bruising, and swelling in the area of treatment. Injections may need to be repeated every few months (Pak 2015; ASOPRS 2015; Mayo Clinic 2014).

5 Novel And Emerging Strategies

Bioidentical Hormone Replacement Therapy

Estrogens have an important role in preserving collagen content, thickness, and moisture of skin, protecting against photoaging and improving wound healing. Declining estrogen levels in postmenopausal women intensify the effects of aging on the skin. Estrogen replacement therapy restores skin thickness and reduces wrinkling by increasing the synthesis of collagen and elastin fibers and inhibiting collagen breakdown. Estrogen replacement can also alleviate skin dryness by enhancing production of skin-hydrating hyaluronic acids. However, long-term use of conventional hormone replacement therapy using non-bioidentical (to humans) equine (horse) estrogens and synthetic progestogens (progestins) is associated with higher risk of breast cancer and cardiovascular diseases (Prentice 2014; Rossouw 2002; Manson 2013).

Bioidentical hormones may be a safer method for replacing hormones that have declined with age. Bioidentical hormones are chemically identical to the hormones produced by the body. Bioidentical estrogens include 17 beta-estradiol, estrone, and estriol. Progesterone is also a bioidentical hormone. Many bioidentical hormone preparations are FDA approved (Holtorf 2009; HHP 2006).

In a study in 59 premenopausal women with signs of skin aging, treatment with topical bioidentical estradiol or estriol for six months resulted in substantial improvement in skin elasticity and firmness. Wrinkle depth and pore sizes were reduced by 61‒100%, and skin moisture increased. Chemical analysis revealed a marked increase in collagen levels in the women’s skin (Schmidt 1996).

More information about bioidentical hormone replacement therapy is available in Life Extension’s Female Hormone Restoration protocol.

Platelet-Rich Plasma

Platelet-rich plasma (PRP) is an emerging technology that can aid in regeneration and healing of bone, tendons, ligaments, and other tissues including facial skin. PRP is derived from a patient’s own blood that has been subjected to a process that isolates and concentrates platelets (Loesch 2014; Yuksel 2014).

PRP, in both topical and injectable forms, has been investigated as a treatment for wrinkles, pigmentation disorders, and photodamaged skin. It is often used in conjunction with other treatments such as laser resurfacing (Loesch 2014; Kim, Je 2011). In a preliminary trial in 10 healthy volunteers, subjects reported that PRP significantly improved their facial skin’s general appearance, firmness, sagging, and wrinkles (Yuksel 2014). In addition, several studies have found the use of PRP with laser therapy was associated with fewer side effects, shorter healing time, and better overall response than laser therapy alone (Loesch 2014).

Adipose-Derived Stem Cells

Adipose tissue is a source of stem cells that can be used to promote wound healing and tissue regeneration. Evidence from animal studies indicates injections of adipose-derived stem cells may be a promising therapy for aging skin (Zhang 2014; Park 2008; Chen, Qin 2014; Mizuno 2012; Charles-de-Sa 2015), and in a single case study in a human subject, adipose-derived stem cell therapy had positive effects on the condition of photodamaged skin (Park 2008).

In a mouse model of skin aging, injection of adipose-derived stem cells under the skin significantly reduced UVB-induced wrinkles by stimulating collagen synthesis and skin thickening (Kim 2009). In another study, injection of adipose-derived stem cells under the skin was shown to exert anti-aging effects in the skin of mice as measured by changes in molecular markers of senescence. Inhibition of advanced glycation end product (AGE) levels by adipose-derived stem cells contributed to skin regeneration during aging (Zhang 2014).

Radiofrequency Resurfacing

Radiofrequency is increasingly being used to treat wrinkles and tighten skin. Radiofrequency devices work by generating heat in deeper layers of the skin, stimulating production of new collagen. This technology is sometimes combined with laser resurfacing methods (Dunbar 2015; Gold 2011; Loesch 2014).

Although questions remain regarding the efficacy of radiofrequency therapy (Araujo 2015), patient satisfaction is reported to be high: In a survey of 5700 radiofrequency treatments, 87% of patients noted immediate skin tightening and 92% reported tightening that lasted six months after treatment (Dover 2007). In addition to its aesthetic applications, radiofrequency technology appears to be beneficial in the treatment of acne, acne scars, keloids, and rosacea (Loesch 2014; Krueger 2013). For example, results of one review indicated patients may see improvements of 25‒75% in acne scars after several treatment sessions. The review noted that radiofrequency treatment has been associated with side effects such as temporary pain, scabbing, bruising, redness, and dryness (Simmons 2014).


Mesotherapy is a procedure in which vitamins, minerals, amino acids, hyaluronic acid, and other substances are injected into the superficial layers of the skin. Mesotherapy injections are meant to increase hydration and activate collagen-producing fibroblasts (Prikhnenko 2015; Savoia 2013).

Mesotherapy, popular in Europe for many years, has recently been receiving more attention in the United States. Clinical trials have provided evidence that mesotherapy treatments can improve skin hydration, texture, and firmness, reducing lines and wrinkles and signs of photoaging (Prikhnenko 2015; Savoia 2013; Konda 2013). In a study involving 55 women with signs of skin aging, a 3-month treatment period with a hyaluronic acid-based mesotherapy formulation with mannitol improved parameters of skin elasticity and complexion radiance compared with control (Baspeyras 2013). Other studies have demonstrated mesotherapy to be an effective treatment for facial rejuvenation (Savoia 2013; Iannitti 2014).

6 Diet And Lifestyle Considerations

Plant-Based, Minimally Processed Diet

Diet is increasingly being recognized as a factor in skin diseases such as acne, atopic dermatitis, psoriasis, and skin cancers (Katta 2014; Heinrich 2011; Piccardi 2009). Diet is also a factor in skin aging. For instance, a diet that leads to persistently elevated blood sugar accelerates the formation of AGEs, resulting in structural changes in the skin such as loss of elasticity and increased stiffness. Also, preformed AGEs, generated by high-heat cooking methods such as grilling, frying, and roasting, can enter the bloodstream and damage skin collagen and elastin. Common herbs and spices including garlic, cloves, oregano, ginger, and cinnamon can inhibit the production of AGEs (Katta 2014).

Many nutrients in plant-based foods, including polyphenols, carotenoids, omega-3 fatty acids, and vitamins A, C, and E, provide protection against UV radiation-induced skin damage. These constituents are found in fruits, vegetables, legumes, cocoa, green tea, coffee, red wine, soy, olive oil, and other plant-based foods (Schagen 2012; Heinrich 2011; Pandel 2013; Piccardi 2009). Many of these foods are found in the Mediterranean diet (OPT 2016).

Caloric Restriction

Caloric restriction—consuming fewer calories while maintaining good dietary nutritional quality—has been shown to retard signs of aging and increase lifespan in animals (Ahmed 2009; Fernandes 1997; Michan 2014). In humans, long-term caloric restriction results in metabolic changes that reduce the risk of multiple age-related diseases including diabetes, cardiovascular disease, and cancer (Steven 2015; Sheth 2015; Rizza 2014; Michan 2014; Bales 2013; Lefevre 2009; Meyer 2006; Fontana 2004; Wing 1994; Stein 2012; Ravussin 2015). Caloric restriction has also been shown to delay skin aging in animals. In rodent studies, caloric restriction was shown to increase the concentration of collagen-producing fibroblasts and affect skin quality (Bhattacharyya 2005; Bhattacharyya 2012). More information is available in Life Extension’s Caloric Restriction protocol.


Sunscreens are commonly used to prevent skin photoaging caused by UV radiation from the sun. Evidence from randomized controlled trials confirms the ability of sunscreens to prevent skin photoaging and skin cancers. For instance, one controlled clinical trial in more than 900 adults showed daily use of sunscreens resulted in no noticeable increase in skin aging after 4.5 years (Hughes 2013; Antoniou 2010; Iannacone 2014). Sunscreens should contain ingredients that provide broad-spectrum protection against both UVA and UVB radiation. Allowing time for sunscreen to be absorbed into the skin before sun exposure is important; sunscreen should be applied 30 minutes before going outside (Lim 2012).

Sleep Hygiene

Lack of sleep may negatively impact collagen formation and skin integrity, in part by inducing a state of chronic low-grade inflammation (Kahan 2010; Besedovsky 2012).

In a study in 60 healthy women, chronic poor sleep quality together with short sleep duration (5 hours or less) was associated with higher skin aging scores and longer recovery time from exposure to UV light, while good sleepers had a 30% better response to a skin barrier challenge (Oyetakin-White 2015).

Life Extension’s Insomnia protocol describes several strategies for improving sleep.

Stress Management

The link between stress and skin conditions is well established. Stress can trigger or worsen numerous inflammatory skin conditions including psoriasis, acne, atopic dermatitis, and contact dermatitis. Skin aging is also impacted by chronic stress (Chen, Lyga 2014).

Chronic physical or psychological stress activates the hypothalamic-pituitary-adrenal axis and promotes release of stress hormones such as cortisol and adrenaline. Sustained excessive levels of cortisol can cause loss of collagen and elastin, leading to skin thinning, easy bruising, impaired wound healing, and water loss (Dunn 2013; Chen, Lyga 2014).

Life Extension’s Stress Management protocol reviews several ways to effectively manage stress.

7 Nutrients

Systemic Interventions

Primary Support

Collagen peptides. Preclinical and clinical evidence has demonstrated that oral intake of collagen peptides reduces wrinkles and improves skin moisture, elasticity, and overall condition, and may help protect against photoaging (Proksch, Schunck 2014; Proksch, Segger 2014; Pei 2008; Pyun 2012; Okawa 2012).

In a double-blind placebo-controlled study in 69 adult women, oral ingestion of a specific formulation of bioactive collagen peptides resulted in significant improvement in skin elasticity. A skin moisturizing effect was also observed in some elderly women. The skin benefits of oral collagen can be long-lasting, particularly in women over age 50 (Proksch, Segger 2014).

In another double-blind placebo-controlled study, in 114 women, the same orally administered preparation of bioactive collagen peptides reduced eye wrinkle volume. Collagen and elastin synthesis in the skin of the treatment group increased 65% and almost 18%, respectively, compared with the placebo group (Proksch, Schunck 2014).

Collagen is also a critical component of hair, contributing to its strength and growth. In fact, hair follicles produce certain types of collagen in greater amounts than are present in skin. And age-related hair thinning and loss appears to be related to a loss of collagen (Katsuoka 1988; AAS 2016; Hamers 2016).

Collagen peptides provide amino acids from which the body can make keratin. Early studies found that consumption of gelatin, a form of hydrolyzed collagen, for three months resulted in nails that had been soft, peeling, and easily broken returning to a normal, healthy appearance. A similar effect was observed in the treatment of brittle nails using gelatin (Schwimmer 1957; Rosenberg 1957; CPCE 2016; Purdue University 2016).

Solubilized keratin. Keratin is a major structural protein in skin, hair, and nails (Miller 1999; Fujikawa 2012; Chamcheu 2011). A novel formulation, Cynatine HNS, has been shown to deliver a highly bioavailable solubilized form of keratin to the skin. In a randomized controlled trial in 50 women, oral ingestion of Cynatine HNS containing 500 mg of solubilized keratin plus vitamins and minerals significantly improved various aspects of skin appearance including skin moisture, elasticity, and smoothness. Also, the depth of wrinkles was significantly reduced compared with baseline and placebo (Beer 2013).

Cynatine HNS has also been shown to significantly improve the condition of hair and nails. In a randomized clinical trial, women who took Cynatine HNS for 90 days had significantly less hair loss compared with the placebo group. Overall hair quality including shininess and brightness improved substantially in the Cynatine HNS group. Also, more women in the Cynatine HNS group reported having hard and robust nails, and fewer in this group had broken and roughened nails (Beer 2014).

Polypodium leucotomos extract. Polypodium leucotomos (P. leucotomos) extract is derived from a tropical fern plant native to Central and South America. Accumulating evidence indicates oral supplementation of P. leucotomos extract provides potent protection against skin photoaging, suggesting it may also have a role in skin cancer prevention (El-Haj 2015). P. leucotomos has also been studied as a treatment for several skin conditions exacerbated by sun exposure including psoriasis, atopic dermatitis, and vitiligo (Winkelmann 2015; Nestor 2015; Bosch 2015; Choudhry 2014).

P. leucotomos extract is a systemic protective agent with an excellent safety profile that may be useful in the prevention of skin cancer. P. leucotomos inhibits generation of reactive oxygen radicals, enhances the body’s own defenses against oxidative stress, reduces UV light-induced DNA mutations, and helps repair sun-induced damage (El-Haj 2015).

Other mechanisms by which P. leucotomos protects against sun damage include anti-inflammatory and immunomodulating effects (Bosch 2015). P. leucotomos also directly inhibits metalloproteinases—enzymes that degrade collagen and elastin—and increases production of tissue inhibitors of metalloproteinases (Saito 1998; Skjot-Arkil 2012; Philips 2009).

Carotenoids. Carotenoids are antioxidant pigments produced by several forms of life (eg, plants and algae), contributing to their characteristic colors. Beta-carotene, lycopene, lutein, zeaxanthin, and astaxanthin are all carotenoids that may play important roles in skin health, particularly by protecting against damage caused by sunlight (photoprotection) (Michalak 2021). In plants and algae, these pigments’ role is to absorb light in the blue-green portion of the visible light spectrum and help facilitate photosynthesis, which is the conversion of light into a form of energy the cells can use (Hashimoto 2016).

  • Beta-carotene. Beta-carotene is a precursor to vitamin A (retinol) with notable food sources that include spinach, carrots, and sweet potatoes. In a randomized-controlled trial, 30 healthy women over age 50 received different dosages of beta-carotene (15 mg RAE or 45 mg RAE) for 90 days. The participants’ skin was evaluated for changes in several measures of skin health. The results showed that, compared with baseline, only those in the lower-dosage group had significant improvements in facial wrinkles, skin elasticity, collagen gene expression, and reductions in DNA damage (Cho 2010).
  • Lycopene. Lycopene is found in the highest concentrations in red fruits such as tomatoes, watermelons, and papayas. In a clinical trial, researchers evaluated the effect that daily supplementation of 15 mg lycopene for three months had on measures of skin health in 50 women aged 35–55. At baseline, four and 12 weeks, skin barrier function was assessed via measurement of the amount of water that passed from inside the body through the skin and evaporated. Other measures of skin status were assessed via questionnaires and expert visual grading of facial markers. The results showed that, compared with baseline, there was a significant improvement in skin barrier function and pore size at 12 weeks and significant improvement in skin tonality, lines and wrinkles, skin smoothness, and skin firmness at four and 12 weeks (Tarshish 2023).
  • Lutein and zeaxanthin. Lutein and zeaxanthin are found in many different plant food sources, seafood, and eggs. They help filter high-energy blue light in human retinas but are also found in human skin cells and thus may be protective against sunlight-induced oxidative damage. In a randomized-controlled trial, 50 healthy men and women between ages 18 and 45 years who had mild-to-moderate dry skin received either a supplement containing 10 mg lutein and 2 mg zeaxanthin or placebo for 12 weeks. Subjects were tested for UV-induced erythema (skin reddening) on their forearm skin prior to and after the intervention. Results showed that the overall skin tone and response to UV radiation improved significantly in the treatment group compared with the placebo group (Juturu 2016).
  • Astaxanthin. Astaxanthin is synthesized by many forms of life; however, a species of algae called Haematococcus pluvialis synthesizes it particularly efficiently. Astaxanthin has been shown clinically to improve the immune and inflammatory response. It is also garnering attention in the context of skin health. Upon absorption through the small intestine, astaxanthin is transported to the skin. Because of its strong free radical-scavenging effects, astaxanthin is believed to have a protective role in skin condition, skin aging, and UV-induced skin deterioration (Davinelli 2018).
  • In a randomized-controlled trial, 23 healthy Japanese participants were recruited to take 4 mg astaxanthin or placebo daily for 10 weeks. The study was designed to assess the protective role of astaxanthin against sun damage. Subjects received a test of UV-induced erythema on their back. The astaxanthin group had a reduced loss of skin moisture in the irradiated area compared with those in the placebo group. In addition, subjective assessments of skin health improved, including “improvement of rough skin” and “texture” in non-irradiated areas (Ito 2018).

    Research also suggests astaxanthin may play a protective role against skin aging. A systematic review and meta-analysis was conducted on nine randomized-controlled trials that evaluated oral astaxanthin and two open-label prospective studies that evaluated topical astaxanthin. Two studies evaluated 2 mg oral astaxanthin daily in combination with tocotrienols and collagen hydrolysate, the other studies used dosages ranging from 4 mg to 12 mg daily. The length of studies ranged from four to 16 weeks. The pooled results showed that astaxanthin supplementation significantly restored moisture content and improved elasticity, but did not significantly decrease wrinkle depth compared with placebo (Zhou 2021).  

Nicotinamide. Nicotinamide—a form of vitamin B3—has been successfully used orally as a safe treatment for a variety of inflammatory skin conditions including acne and rosacea (Niren 2006; Wang 2015). Nicotinamide also appears to be effective in the prevention of skin cancers (Chen 2015; Yiasemides 2009).

In a randomized controlled trial for skin cancer chemoprevention, 12 months of oral supplementation with nicotinamide in high-risk patients yielded significant benefits. Treatment with nicotinamide resulted in a 23% lower rate of new non-melanoma skin cancers and an 11‒20% reduction in incidence of the precancerous lesion actinic keratosis compared with the placebo group (Chen 2015).

In a placebo-controlled trial in healthy volunteers, doses of either 500 or 1500 mg of nicotinamide, administered for 1 week, significantly reduced immunosuppression induced by UV radiation from sunlight (Yiasemides 2009).

Nicotinamide is the precursor of nicotinamide adenine dinucleotide (NAD+), a compound required for energy (ATP) production. UV radiation suppresses DNA repair by depleting cellular energy. Nicotinamide appears to block damage from UV light through mechanisms that involve cellular energy metabolism and DNA repair. By increasing cellular NAD+, nicotinamide combats the decline in cellular energy and DNA repair associated with UV exposure. In rodent models, nicotinamide has prevented UV light-induced cancer (Chen 2015; Yiasemides 2009; Surjana 2012).

Red orange extract. Red orange extract, derived from a mixture of three red orange varieties (Citrus sinensis varieties: Moro, Tarocco, Sanguinello), is rich in cyanidin 3-glycosides—compounds with free radical scavenging properties (Saewan 2015; Delazar 2010). In a study in cultured human skin cells, red orange extract was shown to inhibit production of malondialdehyde—a marker of lipid oxidation (Morini 2000).

Through its ability to inhibit oxidation, red orange extract protects against photoaging. In a study in healthy volunteers, supplementation with 100 mg red orange extract daily for 15 days significantly decreased the degree of skin redness induced by UV radiation (Puglia 2014). In another study, supplementation with 100 mg red orange extract twice daily for 15 days increased protection against UVB-induced skin damage in 18 healthy women. Specifically, skin reddening in response to a specific dose of UVB radiation decreased by about 35% (Bonina 2016).

Phytoceramides. Ceramides are an essential component of the lipid-rich protective layer within the epidermis. Although present in other tissues, ceramides are especially concentrated in the skin where they help maintain normal skin hydration and barrier function. It is well established that low ceramide levels are an important causative factor in diseases of the skin, and it has been suggested that age-related skin dysfunction could also be a result of ceramide deficiency (Rabionet 2014; Di Marzio 2008; Choi 2005). Ceramide concentrations decrease with age and exposure to UV radiation, as from sunlight (Jensen 2005; Bak 2011).

In a randomized trial, 51 women aged 20‒63 years with dry skin were given either 350 mg of a non-GMO wheat extract containing ceramides or placebo for three months. In the ceramide group, a significant increase in skin hydration and an improvement in clinical signs of dryness were observed at the end of 3 months (Guillou 2011).

Additional Support

Vitamin D. Insufficient vitamin D levels have been linked in epidemiologic studies to cardiovascular disease, diabetes, autoimmune disease, neurologic disorders, some cancers, Alzheimer disease, and increased overall mortality (Sage 2010; Clemente-Postigo 2015; Lu'o'ng 2013). Apart from its role in the production of vitamin D, the skin is also a target tissue for vitamin D. In its active form as calcitriol, vitamin D contributes to healthy skin cell renewal and repair, and supports the skin’s immune system (Mostafa 2015; Reichrath 2012; Drake 2011).

Vitamin D deficiency is an epidemic in North America and throughout the world (Palacios 2014; Hagenau 2009). With more frequent sunscreen use and less sun exposure, the skin’s ability to manufacture vitamin D is compromised, making supplemental intake advisable (Holick 2008; Sage 2010).

Biotin. Biotin is a B vitamin shown to improve nail health. In a controlled clinical trial, a 25% increase in nail thickness was demonstrated in patients with brittle nails who were given biotin supplements (Colombo 1990). In another study, 91% of patients with brittle nails who were given 2.5 mg biotin daily for several months showed a clear benefit with firmer and harder nails (Floersheim 1989).

Hair loss is a symptom of biotin deficiency. Patients with alopecia areata, a severe type of hair loss, may require higher-than-normal biotin intake. In one study, children with this condition were treated with the corticosteroid, clobetasol propionate, alone or in combination with biotin and zinc supplementation. After one year of treatment, 33% of those in the zinc and biotin group had complete regrowth of hair, compared with none treated with corticosteroids alone (Camacho 1999; Higdon 2015a).

Silicon. Silicon is an essential trace mineral that plays a critical role in connective tissue health and is believed to factor into the structural integrity of hair, nails, and skin (Martin 2013). It is involved in the synthesis and stabilization of collagen. Collagen concentrations are decreased in silicon-deficient animals (Carlisle 1986; Jugdaohsingh 2007; Seaborn 2002; Seaborn 1993). Brittle nails may respond to supplementation with silicon (Scheinfeld 2007).

Zinc. Zinc is an essential mineral for healthy skin and hair: it stabilizes cell membranes, is necessary for proper wound healing, and is concentrated in hair follicles. Six percent of the body’s zinc is present in the skin (Angelo 2013).

In multiple clinical trials, zinc has been used successfully to treat alopecia, an immune-mediated type of hair loss. These trials have used months to years of zinc treatment. In one of these studies, dry scaly skin also resolved with zinc treatment (Sonnichsen 1984; Wolowa 1978; Slonim 1992; Ead 1981; Camacho 1999).

Pantothenic acid. Also known as vitamin B5, pantothenic acid is an essential nutrient in the diet and is important to wound healing. In the form calcium D-pantothenate, vitamin B5 increased healing in a preclinical wound-repair model. In a laboratory model, pantothenic acid deficiency inhibited skin keratinocyte proliferation (Higdon 2015b).

Mice that are deficient in pantothenic acid have been shown to develop gray fur and skin irritation, which resolved upon vitamin B5 supplementation (Higdon 2015b).

Omega-3 fatty acids. Omega-3 fatty acids help protect skin against the damaging effects of UV light. Results from preclinical and clinical trials indicate omega-3 fatty acids have both photoprotective and anti-skin-aging effects (Pilkington 2013; Kim 2006; Kim 2005; Angelo 2012).

In a controlled clinical trial, an omega-3 fatty acid supplement rich in eicosapentaenoic acid (EPA) was found to protect against immunosuppression induced by solar-simulated UV radiation in human skin. Supplementation with fish oil rich in omega-3 fats modifies the fatty acid composition of cell membranes by displacing the omega-6 fatty acid arachidonic acid. This leads to a decline in levels of arachidonic acid-derived prostaglandins—cell-signaling molecules that can intensify the inflammation and immunosuppression generated following UV exposure (Surette 2008; Angelo 2012; James 2000; Pilkington 2013).

Lycopene. Lycopene, which is abundant in tomatoes and tomato-based products, can powerfully reduce oxidative stress in skin (Evans 2010). This property may also confer protection against UV light-induced damage(Schagen 2012; Pandel 2013). In a controlled clinical trial, subjects were given either a drink containing 5.7 mg of lycopene, along with several other tomato-derived antioxidants, or placebo for 26 days. At the end of the trial, blood levels of the inflammatory mediator tumor necrosis factor-alpha were over 34% lower in the group that consumed the tomato-based drink (Riso 2006).

In a randomized controlled trial, 20 women ingested 16 mg of tomato-based lycopene daily for 12 weeks. After being exposed to UV radiation, the lycopene-supplemented group was substantially protected against skin reddening compared with the control group. Researchers concluded that lycopene effectively protected the skin from acute and potentially long-term photodamage (Rizwan 2011).

Resveratrol. Resveratrol is a natural compound found in several plants and foodstuffs such as grapes, peanuts, berries, red wine, and Japanese knotweed. In laboratory studies, resveratrol has been demonstrated to effectively neutralize free radicals, inhibit oxidation of low-density lipoprotein, and suppress inflammation (Higdon 2015c).

Resveratrol holds promise as a safe and effective agent against a wide variety of skin conditions, including skin aging and skin cancers (Ndiaye 2011). In a study in tumor-susceptible mice, oral resveratrol markedly suppressed progression of malignant tumors induced by UVB irradiation. Resveratrol also markedly inhibited the malignant conversion of benign papillomas (skin tags) to squamous cell carcinomas (Kim, Back 2011).

In another study, resveratrol reduced tumor growth and metastasis in a mouse model of melanoma. In the same investigation, resveratrol effectively reduced the invasiveness and migration of cultured mouse melanoma cells (Bhattacharya 2011). These results suggest resveratrol may have potential as a treatment for melanoma.

Green tea polyphenols. Green tea polyphenols have been shown to protect against sunburn, immunosuppression, and skin aging caused by UV radiation (Yusuf 2007). In a placebo-controlled trial in 60 women with healthy skin, participants who consumed a beverage with green tea polyphenols had less UV-induced skin redness and better overall skin characteristics. Specific skin variables that improved in the treatment group included elasticity, roughness, scaling, density, and hydration. The ability of plant polyphenols to absorb UV light may account for their UV protective effects (Heinrich 2011).

Heat exposure (eg, from UV radiation) causes damage to the skin’s structural framework by boosting production of collagen-degrading matrix metalloproteinases, resulting in premature skin aging. In a study in human skin fibroblasts, epigallocatechin-3-gallate (EGCG)—the major polyphenolic compound in green tea—markedly inhibited heat shock-induced production of matrix metalloproteinase-1. These results suggest EGCG might be useful in the prevention and treatment of thermal skin aging (Kim 2013).

Topical Interventions

Primary Support

Hyaluronic acid. Hyaluronic acid, a natural component of many tissues, is a large polysaccharide that efficiently binds water molecules. Hyaluronic acid plays an important role in keeping the skin properly moisturized (Sudha 2014). Hyaluronic acid injections are a popular dermal filler, helping correct cosmetic facial changes associated with aging (Franca Wanick 2016; Brandt 2008). Topically applied hyaluronic acid has been shown to improve skin hydration and elasticity while also significantly reducing wrinkle depth (Pavicic 2011).

In a test conducted by Rutgers University scientists, skin cells treated with a specially modified hyaluronic acid formulation (Hylasome) retained six times more moisture compared with cells treated with regular hyaluronic acid. Hylasome was also shown to suppress oxidative stress four times more effectively than an unmodified hyaluronic acid preparation, suggesting an additional mechanism by which the likelihood of skin damage and wrinkles may be reduced (Vantage 2016).

Matrixyl synthe’6. Matrixyl synthe’6 is a novel tripeptide that promotes the synthesis of six key components of the skin’s structural framework, or matrix: collagen types I, III, and IV, hyaluronic acid, fibronectin, and laminin (Sederma 2016).

In a two-month clinical trial, Matrixyl synthe’6 noticeably decreased wrinkle volume and depth. Forehead and crow’s feet wrinkles were especially smoothed (Sederma 2016).

Topical vitamin C. Vitamin C is a powerful free radical scavenger that also plays an essential role in collagen synthesis. Since skin concentrations of vitamin C decrease with age, restoring levels directly in the skin may reduce facial wrinkles and improve the appearance of photoaged skin. In fact, topical application of vitamin C increases concentrations of the vitamin in the skin 20‒40 times more effectively than oral supplementation. Multiple clinical trials using topical vitamin C have shown this treatment’s ability to improve subjective and objective appearance of photoaged facial skin (Sauermann 2004; Rhie 2001; Traikovich 1999; Humbert 2003; Fitzpatrick 2002; Burke 2004).

In a 12-week placebo-controlled trial in over 20 volunteers, topical vitamin C significantly reduced fine lines and wrinkles in aged skin. Oxidative stress in the skin was also substantially reduced (Raschke 2004). In another randomized trial performed over six months, topical vitamin C cream decreased deep furrows and improved the appearance of photodamaged skin compared with the control (Humbert 2003).

Additional Topical Support

Melatonin. Regulation of the body’s sleep-wake cycle is in part dependent upon the hormone melatonin. The pineal gland in the brain normally releases melatonin in the evenings in preparation for sleep. Up until the last few decades, melatonin was thought to be primarily isolated to pineal synthesis and function narrowly in the regulation of circadian rhythms. But more recently, melatonin has been observed at sites far removed from the pineal gland, including bile fluid, bone marrow, ovaries, white blood cells, and skin (Fischer 2008).

As with its sites of synthesis and actions, the biological activity of melatonin has come into greater light recently. For example, melatonin is now recognized as a potent antioxidant capable not only of neutralizing free radicals directly, but also stimulating other endogenous antioxidant defense systems. In fact, some researchers have employed the term melatonergic antioxidative system when describing these biochemical interactions (Fischer 2008).

Melatonin exerts a broad range of activity in the skin, which has been shown to express melatonin receptors and is another site of melatonin synthesis outside the pineal gland. Studies have shown that melatonin protects against UV-induced skin reddening and DNA damage, increases levels of glutathione (a powerful endogenous antioxidant), and suppresses growth of carcinoma and melanoma skin cancers (Fischer 2008).

In a randomized double-blind trial, topically applied melatonin was shown to protect against UV irradiation of the skin. The effect was dose-dependent and was enhanced when the melatonin was combined with alpha-tocopherol and vitamin C. The melatonin formula was applied 30 minutes before the skin was exposed to UV radiation (Dreher 1998).

DHEA. Dehydroepiandrosterone (DHEA) is an adrenal hormone involved in many physiological functions; it is also a precursor to more potent androgens such as testosterone. DHEA levels decline with age, and this decline has been associated with several health conditions such as depression, atherosclerosis, osteoporosis, frailty, and sexual dysfunction (Samaras 2015; Shin 2005).

Topical DHEA application has been shown to exert anti-aging effects in the skin. In a 13-week trial that enrolled 75 postmenopausal women, topical DHEA application led to increases in levels of proteins involved in collagen synthesis. The investigators concluded that “…topical DHEA could be used as an efficient and physiological anti-ageing skin agent” (El-Alfy 2010). In another clinical trial, a 1% DHEA topical formulation applied for four months improved several subjective measures of skin health (Nouveau 2008).

In a trial in which subjects applied a 5% DHEA formulation 3 times weekly for four weeks, levels and expression of the collagen precursor procollagen alpha 1 increased. This study also found that the topical DHEA applications decreased expression of matrix metalloproteinase-1, and increased expression of transforming growth factor-beta 1 and tissue growth factor messenger RNA (Shin 2005).

DMAE. DMAE (2-dimethylaminoethanol) is an analog of the B vitamin choline and a precursor of the neurotransmitter acetylcholine. In a randomized clinical study, topical DMAE gel applied to the face for 16 weeks safely and effectively reduced forehead lines and wrinkles around the eyes. Lip shape and fullness, as well as overall skin appearance, also improved with DMAE gel (Grossman 2005).

Vegetal filling spheres. Vegetal filling spheres, composed of a plant-based biopolymer, help smooth wrinkled skin by promoting hydration. These tiny spheres penetrate the skin surface where they swell up and fill in wrinkles and lines (BASF 2014).

Salicylic acid. Salicylic acid is a safe and effective peeling agent used to treat various skin conditions including acne, freckles, and liver spots (Arif 2015; Mammone 2006). It has anti-inflammatory properties and has been shown in a preclinical trial to protect skin against sun damage (Arif 2015).

Pichia-fermented resveratrol. Topical resveratrol has been shown to have anti-inflammatory and anti-aging effects (Farris 2013; Puizina-Ivic 2010). In a mouse model of skin cancer, topical resveratrol inhibited the development of tumors (Jang 1997).

Scientists have now developed a more potent topical preparation of resveratrol that is fermented by pichia pastoris yeast. In a placebo-controlled trial, facial treatment with pichia-fermented resveratrol resulted in marked improvements in skin hydration, tone, and texture as well as an improvement in the appearance of wrinkles (Metabiotics 2009).

Botanimoist AMS apple saccharides. Botanimoist AMS “Apple Moisturizing Saccharide” is extracted from dried apples and has been shown to help moisturize the skin. In a placebo-controlled human trial, a single topical application of Botanimoist AMS increased skin hydration by 89% in 30 minutes. After six hours, skin hydration remained 33% higher than controls (Botanigenics 2016).

Snow algae. Found primarily in polar and mountain regions around the world, snow algae are microorganisms that possess anti-aging properties. Snow algae extract has been shown to activate two master “switches” that extend lifespan: the Klotho gene for longevity and the energy sensor AMPK (adenosine monophosphate-activated protein kinase) (Lukes 2014; Snow-Algae 2014a; Snow-Algae 2014b).

Topically applied snow algae may enhance skin appearance and function. In a clinical trial, snow algae powder strengthened skin barrier function, increased skin hydration, and reduced wrinkles. This study took place during winter, a time when cold can increase stress on and water loss from skin (Snow-Algae 2014c).

Alpine rose stem cell extract. The epidermis (skin surface) undergoes a renewal process approximately every two months (Koster 2009). This significant ability of the skin to renew itself relies on a reservoir of epidermal stem cells (Bickenbach 2006). These epidermal stem cells contribute to repair and healing of skin injury, restoring the integrity and functions of the skin (Morasso 2005; Zouboulis 2008; Charruyer 2011; Margadant 2010).

The Alpine rose (Rhododendron ferrugineum) flourishes in the Swiss Alps and the Pyrenees where it endures harsh environmental stresses such as extreme cold and dryness and searing UV rays (Louis 2010; Peng 2008). An ingredient based on stem cells from Alpine rose leaves has been shown to protect epidermal stem cells from UV stress. In an experimental study, epidermal stem cells treated with Alpine rose stem cells were better able to maintain their integrity and were protected from UV-induced stress (PhytoCellTec 2010).

In a clinical trial, treatment of facial skin with Alpine rose stem cell extract, in participants exposed to extreme environmental conditions in the European Alps, significantly improved skin appearance. Wrinkles were less visible in 45% of treated subjects, water loss from skin was reduced by 39%, and decreased redness and irritation was noticed by 54% of subjects (PhytoCellTec 2010).

Palmitoyl dipeptide-5. Palmitoyl dipeptide-5 is a novel peptide that stimulates collagen synthesis in the dermal-epidermal junction, an area of tissue that joins the outer layer of skin (epidermis) with the layer underneath (dermis). In one trial, a topical mixture containing palmitoyl dipeptide-5 was shown to significantly increase skin firmness, tonicity, and suppleness after two months (Centerchem 2016).

Palmitoyl tripeptide-5. Palmitoyl tripeptide-5 is a peptide shown to activate transforming growth factor beta, a protein that boosts collagen synthesis (Lijnen 2002). In a three-month study in 37 women with signs of skin aging, treatment with a topical formula containing palmitoyl tripeptide-5 demonstrated both immediate (within minutes) and long-term improvements in the appearance of fine and coarse wrinkles (Trookman 2009).

Similarly, in a 12-week study, a serum containing palmitoyl tripeptide-5 produced significant reductions in fine and coarse wrinkles in women with facial photodamage. Skin texture, tone, and radiance were improved as well (Sonti 2013).

Acetyl tetrapeptide-2. Acetyl tetrapeptide-2 is a peptide shown to significantly improve elastin synthesis in human skin fibroblasts. In a clinical study in volunteers aged 50‒60 with saggy facial skin, treatment with acetyl tetrapeptide-2 resulted in visibly firmer facial skin. It also increased the formation of type I collagen by 47% (Lipotec 2013).


  • Jul: Added section on carotenoids to Nutrients


  • Sep: Comprehensive update & review

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

AAS. Amino Acid Studies. Benefits: Hair Loss and Preention with amino acids. http://aminoacidstudies.org/hair-loss/. Accessed 5/6/2016

Ahmed T, Das SK, Golden JK, Saltzman E, Roberts SB, Meydani SN. Calorie restriction enhances T-cell-mediated immune response in adult overweight men and women. The journals of gerontology. Series A, Biological sciences and medical sciences. Nov 2009;64(11):1107-1113.

Alkhawam L, Alam M. Dermabrasion and microdermabrasion. Facial plastic surgery : FPS. Dec 2009;25(5):301-310.

Amaro-Ortiz A, Yan B, D'Orazio JA. Ultraviolet radiation, aging and the skin: prevention of damage by topical cAMP manipulation. Molecules (Basel, Switzerland). 2014;19(5):6202-6219.

Angelo G. Oregon State University. Linus Pauling Institute. Micronutrient Center. Essential Fatty Acids and Skin Health http://lpi.oregonstate.edu/mic/micronutrients-health/skin-health/nutrient-index/essential-fatty-acids#functions February 2.

Angelo G.  Linus Pauling Institute. Micronutrient Information Center. Minerals and Skin Health. http://lpi.oregonstate.edu/mic/micronutrients-health/skin-health/nutrient-index/minerals. 1/2013. Accessed 5/9/2016.

Antoniou C, Kosmadaki MG, Stratigos AJ, Katsambas AD. Photoaging: prevention and topical treatments. Am J Clin Dermatol. 2010;11(2):95-102.

Araujo AR, Soares VP, Silva FS, Moreira Tda S. Radiofrequency for the treatment of skin laxity: mith or truth. Anais brasileiros de dermatologia. Sep-Oct 2015;90(5):707-721.

Arif T. Salicylic acid as a peeling agent: a comprehensive review. Clin Cosmet Investig Dermatol. 2015;8:455-461.

Ascenso A, Ribeiro H, Marques HC, Oliveira H, Santos C, Simoes S. Is tretinoin still a key agent for photoaging management? Mini reviews in medicinal chemistry. 2014;14(8):629-641.

ASDS. American Society for Dermatologic Surgery. Chemical Peels. https://www.asds.net/ChemicalPeelsInformation.aspx. Copyright 2016a. Accessed 9/13/2016.

ASDS. American Society for Dermatologic Surgery. Laser Resurfacing. https://www.asds.net/LaserResurfacingInformation.aspx. Copyright 2016b. Accessed 3/7/2016

ASOPRS. American Society of Ophthalmic Plastic & Reconstructive Surgery. Restylane. http://www.asoprs.org/i4a/pages/index.cfm?pageid=3672. Copyright 2015. Accessed 9/13/2016.

ASPS. American Society of Plastic Surgeons. Cosmetic page. Chemical Peel: Minimally Invasive Procedure. http://www.plasticsurgery.org/cosmetic-procedures/chemical-peel.html. Copyright 2016a. Accessed 9/13/2016.

ASPS. American Society of Plastic Surgeons. Cosmetic page. Laser Skin Resurfacing. http://www.plasticsurgery.org/cosmetic-procedures/laser-skin-resurfacing.html. Copyright 2016b. Accessed 3/7/2016.

ASPS. American Society of Plastic Surgeons. Microdermabrasian Treatments: Microdermabrasion risks and safety. http://www.plasticsurgery.org/cosmetic-procedures/microdermabrasion.html?sub=Microdermabrasion+risks+and+safety#content. Copyright 2016c. Accessed 7/19/2016.

Bak H, Hong SP, Jeong SK, Choi EH, Lee SE, Lee SH, Ahn SK. Altered epidermal lipid layers induced by long-term exposure to suberythemal-dose ultraviolet. International journal of dermatology. Jul 2011;50(7):832-837.

Baldwin HE, Nighland M, Kendall C, Mays DA, Grossman R, Newburger J. 40 years of topical tretinoin use in review. Journal of drugs in dermatology: JDD. Jun 1 2013;12(6):638-642.

Bales CW, Kraus WE. Caloric restriction: implications for human cardiometabolic health. J Cardiopulm Rehabil Prev. Jul-Aug 2013;33(4):201-208.

BASF. Plant-based microspheres that fill in wrinkles and lines: Filling Spheres vegetal. http://www.standort-ludwigshafen.basf.de/group/corporate/site-ludwigshafen/en/brand/FILLING_SPHERES_VEGETAL. Copyright 2014. Accessed 4/6/2016

Baspeyras M, Rouvrais C, Liegard L, et al. Clinical and biometrological efficacy of a hyaluronic acid-based mesotherapy product: a randomised controlled study. Archives for dermatological research. Archiv fur dermatologische Forschung. Oct 2013;305(8):673-682.

Baud S, Duca L, Bochicchio B, et al. Elastin peptides in aging and pathological conditions. Biomolecular concepts. Feb 2013;4(1):65-76.

Baumann L. Skin ageing and its treatment. The Journal of pathology. Jan 2007;211(2):241-251.

Beer C, Wood S, Veghte RH. A clinical trial to investigate the effect of Cynatine HNS on hair and nail parameters. TheScientificWorldJournal. 2014;2014:641723.

Beer C, Wood S, Veghte RH. A randomized, double-blind, placebo-controlled clinical trial to investigate the effect of Cynatine(®) HNS on skin characteristics. Int J Cosmet Sci. Dec 2013;35(6):608-612.

Besdine RW. Merck Manual. Consumer Version. Changes in the Body With Aging. http://www.merckmanuals.com/home/older-people’s-health-issues/the-aging-body/changes-in-the-body-with-agi. Copyright 2016. Accessed 9/13/2016.

Besedovsky L, Lange T, Born J. Sleep and immune function. Pflugers Arch. Jan 2012;463(1):121-137.

Bhattacharya S, Darjatmoko SR, Polans AS. Resveratrol modulates the malignant properties of cutaneous melanoma through changes in the activation and attenuation of the antiapoptotic protooncogenic protein Akt/PKB. Melanoma research. Jun 2011;21(3):180-187.

Bhattacharyya TK, Jackson P, Patel MK, Thomas JR. Epidermal cell proliferation in calorie-restricted aging rats. Current aging science. Jul 2012;5(2):96-104.

Bhattacharyya TK, Merz M, Thomas JR. Modulation of cutaneous aging with calorie restriction in Fischer 344 rats: a histological study. Archives of facial plastic surgery. Jan-Feb 2005;7(1):12-16.

Bickenbach JR, Stern MM, Grinnell KL, Manuel A, Chinnathambi S. Epidermal stem cells have the potential to assist in healing damaged tissues. The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. Sep 2006;11(1):118-123.

Bonina F, Puglia C. Effect Of The Supplementation With Red Orange Complex On Ultraviolet-Induced Skin Damage In Human Volunteers. BIONAP: Bioactive Natural Products. Department of Pharmaceutical Sciences - University of Catania. Accessed 5/24/2016

Borg M, Brincat S, Camilleri G, Schembri-Wismayer P, Brincat M, Calleja-Agius J. The role of cytokines in skin aging. Climacteric : the journal of the International Menopause Society. Oct 2013;16(5):514-521.

Bosch R, Philips N, Suarez-Perez JA, Juarranz A, Devmurari A, Chalensouk-Khaosaat J, Gonzalez S. Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals. Antioxidants (Basel, Switzerland). 2015;4(2):248-268.

Botanigenics. Product monograph. Botanimoist AMS. Accessed 2/3/2016

Brandt FS, Cazzaniga A. Hyaluronic acid gel fillers in the management of facial aging. Clinical interventions in aging. 2008;3(1):153-159.

Burke KE. Photodamage of the skin: protection and reversal with topical antioxidants. Journal of cosmetic dermatology. Jul 2004;3(3):149-155.

Calleja-Agius J, Brincat M, Borg M. Skin connective tissue and ageing. Best practice & research. Clinical obstetrics & gynaecology. Oct 2013;27(5):727-740.

Calleja-Agius J, Muscat-Baron Y, Brincat MP. Skin ageing. Menopause international. Jun 2007;13(2):60-64.

Camacho FM, Garcia-Hernandez MJ. Zinc aspartate, biotin, and clobetasol propionate in the treatment of alopecia areata in childhood. Pediatric dermatology. Jul-Aug 1999;16(4):336-338.

Carlisle EM. Silicon as an essential trace element in animal nutrition. Ciba Foundation symposium. 1986;121:123-139.

Carniol PJ, Hamilton MM, Carniol ET. Current Status of Fractional Laser Resurfacing. JAMA facial plastic surgery. Sep-Oct 2015;17(5):360-366.

Centerchem. SYN®-TACKS. http://www.centerchem.com/Products/syn-tacks/. Copyright 2016. Accessed 9/13/2016.

Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H. Keratin gene mutations in disorders of human skin and its appendages. Archives of biochemistry and biophysics. Apr 15 2011;508(2):123-137.

Charles-de-Sa L, Gontijo-de-Amorim NF, Maeda Takiya C, et al. Antiaging treatment of the facial skin by fat graft and adipose-derived stem cells. Plastic and reconstructive surgery. Apr 2015;135(4):999-1009.

Charruyer A, Ghadially R. What's new in dermatology: epidermal stem cells. G Ital Dermatol Venereol. Feb 2011;146(1):57-67.

Chen AC, Martin AJ, Choy B, et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. The New England journal of medicine. Oct 22 2015;373(17):1618-1626.

Chen L, Qin F, Ge M, Shu Q, Xu J. Application of adipose-derived stem cells in heart disease. Journal of cardiovascular translational research. Oct 2014;7(7):651-663.

Chen Y, Lyga J. Brain-skin connection: stress, inflammation and skin aging. Inflammation & allergy drug targets. 2014;13(3):177-190.

Cho S, Lee DH, Won CH, et al. Differential effects of low-dose and high-dose beta-carotene supplementation on the signs of photoaging and type I procollagen gene expression in human skin in vivo. Dermatology. 2010;221(2):160-71. doi:10.1159/000305548.

Choi MJ, Maibach HI. Role of ceramides in barrier function of healthy and diseased skin. Am J Clin Dermatol. 2005;6(4):215-223.

Choudhry SZ, Bhatia N, Ceilley R, Hougeir F, Lieberman R, Hamzavi I, Lim HW. Role of oral Polypodium leucotomos extract in dermatologic diseases: a review of the literature. Journal of drugs in dermatology: JDD. Feb 2014;13(2):148-153.

CIHR. Canadian Institute of Health Research. DrugBank. Tretinoin. http://www.drugbank.ca/drugs/DB00755. Last updated 9/13/2016. Accessed 9/13/2016.

Clemente-Postigo M, Munoz-Garach A, Serrano M, et al. Serum 25-hydroxyvitamin D and adipose tissue vitamin D receptor gene expression: relationship with obesity and type 2 diabetes. The Journal of clinical endocrinology and metabolism. Apr 2015;100(4):E591-595.

Colombo VE, Gerber F, Bronhofer M, Floersheim GL. Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy. J Am Acad Dermatol. Dec 1990;23(6 Pt 1):1127-1132.

CPCE. Collagen Peptide Clinical Evidence. http://www.humanclinicals.org/collagen-peptide-1/. Accessed 5/9/2016

Culp L, Moradi Tuchayi S, Alinia H, Feldman SR. Tolerability of Topical Retinoids: Are There Clinically Meaningful Differences Among Topical Retinoids? Journal of cutaneous medicine and surgery. Nov-Dec 2015;19(6):530-538.

Dahl MV. NEJM Journal Watch [online]. Fragility in Aged Skin - It's Not the Fibroblasts http://www.jwatch.org/jd201003050000002/2010/03/05/fragility-aged-skin-its-not-fibroblasts. 5/5/2010. Accessed 9/13/2016.

Davinelli S, Nielsen ME, Scapagnini G. Astaxanthin in Skin Health, Repair, and Disease: A Comprehensive Review. Nutrients. Apr 22 2018;10(4)doi:10.3390/nu10040522.

Delazar A, Khodaie L, Afshar J, Nahar L, Sarker SD. Isolation and free-radical-scavenging properties of cyanidin 3-O-glycosides from the fruits of Ribes biebersteinii Berl. Acta pharmaceutica (Zagreb, Croatia). Mar 2010;60(1):1-11.

Di Marzio L, Cinque B, Cupelli F, De Simone C, Cifone MG, Giuliani M. Increase of skin-ceramide levels in aged subjects following a short-term topical application of bacterial sphingomyelinase from Streptococcus thermophilus. International journal of immunopathology and pharmacology. Jan-Mar 2008;21(1):137-143.

Dover JS, Zelickson B. Results of a survey of 5,700 patient monopolar radiofrequency facial skin tightening treatments: assessment of a low-energy multiple-pass technique leading to a clinical end point algorithm. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. Aug 2007;33(8):900-907.

Drake VJ. Oregon State University. Linus Pauling Institute. Micronutreint Center. Vitamin D and Skin Health. http://lpi.oregonstate.edu/mic/micronutrients-health/skin-health/nutrient-index/vitamin-D#reference40. 11/2011. Accessed 9/13/2016.

Dreher F, Gabard B, Schwindt DA, Maibach HI. Topical melatonin in combination with vitamins E and C protects skin from ultraviolet-induced erythema: a human study in vivo. Br J Dermatol. Aug 1998;139(2):332-339.

Dunbar SW, Goldberg DJ. Radiofrequency in Cosmetic Dermatology: An Update. Journal of drugs in dermatology: JDD. Nov 1 2015;14(11):1229-1238.

Dunn JH, Koo J. Psychological Stress and skin aging: a review of possible mechanisms and potential therapies. Dermatology online journal. Jun 2013;19(6):18561.

Ead RD. Oral zinc sulphate in alopacia areata-a double blind trial. Br J Dermatol. Apr 1981;104(4):483-484.

Edwards PC, Fantasia JE. Review of long-term adverse effects associated with the use of chemically-modified animal and nonanimal source hyaluronic acid dermal fillers. Clinical interventions in aging. 2007;2(4):509-519.

El-Alfy M, Deloche C, Azzi L, et al. Skin responses to topical dehydroepiandrosterone: implications in antiageing treatment? Br J Dermatol. Nov 2010;163(5):968-976.

El-Domyati M, Hosam W, Abdel-Azim E, Abdel-Wahab H, Mohamed E. Microdermabrasion: a clinical, histometric, and histopathologic study. Journal of cosmetic dermatology. Jun 29 2016.

El-Haj N, Goldstein N. Sun protection in a pill: the photoprotective properties of Polypodium leucotomos extract. International journal of dermatology. Mar 2015;54(3):362-366.

Evans JA, Johnson EJ. The role of phytonutrients in skin health. Nutrients. Aug 2010;2(8):903-928.

Farage MA, Miller KW, Elsner P, Maibach HI. Characteristics of the Aging Skin. Advances in wound care. Feb 2013;2(1):5-10.

Farris P, Krutmann J, Li YH, McDaniel D, Krol Y. Resveratrol: a unique antioxidant offering a multi-mechanistic approach for treating aging skin. Journal of drugs in dermatology : JDD. Dec 2013;12(12):1389-1394.

FDA. U.S. Food and Drug Administration. Medical Devices page. Restylane Silk Injectable Gel - P040024/S072. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm403393.htm. Last updated 1/11/2016. Accessed 4/26/2016.

Felipe DL, Hempe JM, Liu S, Matter N, Maynard J, Linares C, Chalew SA. Skin intrinsic fluorescence is associated with hemoglobin A(1c )and hemoglobin glycation index but not mean blood glucose in children with type 1 diabetes. Diabetes care. Aug 2011;34(8):1816-1820.

Fernandes G, Venkatraman JT, Turturro A, Attwood VG, Hart RW. Effect of food restriction on life span and immune functions in long-lived Fischer-344 x Brown Norway F1 rats. Journal of clinical immunology. Jan 1997;17(1):85-95.

Fischer TW, Slominski A, Zmijewski MA, Reiter RJ, Paus R. Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair. Experimental dermatology. Sep 2008;17(9):713-730.

Fitzpatrick RE, Rostan EF. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. Mar 2002;28(3):231-236.

Floersheim GL. [Treatment of brittle fingernails with biotin]. Zeitschrift fur Hautkrankheiten. Jan 15 1989;64(1):41-48.

Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proceedings of the National Academy of Sciences of the United States of America. Apr 27 2004;101(17):6659-6663.

Franca Wanick FB, Almeida Issa MC, Luiz RR, Soares Filho PJ, Olej B. Skin Remodeling Using Hyaluronic Acid Filler Injections in Photo-Aged Faces. Dermatologic surgery: official publication for American Society for Dermatologic Surgery [et al.]. Mar 2016;42(3):352-359.

Fujikawa H, Fujimoto A, Farooq M, Ito M, Shimomura Y. Characterization of the human hair keratin-associated protein 2 (KRTAP2) gene family. The Journal of investigative dermatology. Jul 2012;132(7):1806-1813.

Geng A, Weinstock MA, Hall R, et al. Tolerability of high-dose topical tretinoin: the Veterans Affairs Topical Tretinoin Chemoprevention Trial. British Journal of Dermatology. 2009;161(4):918-924.

Giesen M, Gruedl S, Holtkoetter O, Fuhrmann G, Koerner A, Petersohn D. Ageing processes influence keratin and KAP expression in human hair follicles. Experimental dermatology. Sep 2011;20(9):759-761.

Gkogkolou P, Bohm M. Advanced glycation end products: Key players in skin aging? Dermato-endocrinology. Jul 1 2012;4(3):259-270.

Gold MH. Medscape Multispecialty. The Increasing Use of Nonablative Radiofredquency in the Rejuvenation of the Skin. Vol. 2016. 2011.

Gold MH. Use of hyaluronic acid fillers for the treatment of the aging face. Clinical interventions in aging. 2007;2(3):369-376.

Grossman R. The role of dimethylaminoethanol in cosmetic dermatology. Am J Clin Dermatol. 2005;6(1):39-47.

Guillou S, Ghabri S, Jannot C, Gaillard E, Lamour I, Boisnic S. The moisturizing effect of a wheat extract food supplement on women's skin: a randomized, double-blind placebo-controlled trial. Int J Cosmet Sci. Apr 2011;33(2):138-143.

Gupta MA, Gilchrest BA. Psychosocial aspects of aging skin. Dermatologic clinics. Oct 2005;23(4):643-648.

Hagenau T, Vest R, Gissel TN, Poulsen CS, Erlandsen M, Mosekilde L, Vestergaard P. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. Jan 2009;20(1):133-140.

Halbina A, Trznadel-Grodzka E, Rotsztejn H. Fractional laser therapy - the next step in alleviating the symptoms of skin aging (own observations). Przeglad menopauzalny = Menopause review. May 2014;13(2):132-135.

Hamers L. One reason your hair is thinning? Some of it turns into skin. Science: American Academy for the Advancement of Science. http://www.sciencemag.org/news/2016/02/one-reason-your-hair-thinning-some-it-turns-skin. 2/4/2016. Accessed 5/6/2016

Hashimoto H, Uragami C, Cogdell RJ. Carotenoids and Photosynthesis. Sub-cellular biochemistry. 2016;79:111-39. doi:10.1007/978-3-319-39126-7_4.

Hassan KM, Benedetto AV. Facial skin rejuvenation: ablative laser resurfacing, chemical peels, or photodynamic therapy? Facts and controversies. Clinics in dermatology. Nov-Dec 2013;31(6):737-740.

Heinrich U, Moore CE, De Spirt S, Tronnier H, Stahl W. Green tea polyphenols provide photoprotection, increase microcirculation, and modulate skin properties of women. The Journal of nutrition. Jun 2011;141(6):1202-1208.

Hexsel C, Hexsel D, Porto MD, Schilling J, Siega C. Botulinum toxin type A for aging face and aesthetic uses. Dermatologic therapy. Jan-Feb 2011;24(1):54-61.

HHP. Harvard Health Publications. Harvard Medical School. What are bioidentical hormones? http://www.health.harvard.edu/womens-health/what-are-bioidentical-hormones. Copyright 2016. Accessed 9/13/2016.

Higdon J. Linus Pauling Institute. Micronutrient Information Center. Biotin. http://lpi.oregonstate.edu/mic/vitamins/biotin. Last updated 10/21/2015a. Accessed 5/9/2016

Higdon J. Linus Pauling Institute. Micronutrient Information Center. Pantothenic Acid: Wound Healing. http://lpi.oregonstate.edu/mic/vitamins/pantothenic-acid#wound-healing-treatment. Last updated 7/2015b. Accessed 5/9/2016

Higdon J. Linus Pauling Institute. Micronutrient Center. Resveratrol. http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/resveratrol#biological-activities. Last updated 6/11/2015c. Accessed 9/13/2016.

Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. The American journal of clinical nutrition. Apr 2008;87(4):1080s-1086s.

Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgraduate medicine. Jan 2009;121(1):73-85.

Hughes MC, Williams GM, Baker P, Green AC. Sunscreen and prevention of skin aging: a randomized trial. Ann Intern Med. Jun 4 2013;158(11):781-790.

Humbert PG, Haftek M, Creidi P, et al. Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo. Experimental dermatology. Jun 2003;12(3):237-244.

Iannacone MR, Hughes MC, Green AC. Effects of sunscreen on skin cancer and photoaging. Photodermatology, photoimmunology & photomedicine. Apr-Jun 2014;30(2-3):55-61.

Iannitti T, Morales-Medina JC, Coacci A, Palmieri B. Experimental and Clinical Efficacy of Two Hyaluronic Acid-based Compounds of Different Cross-Linkage and Composition in the Rejuvenation of the Skin. Pharmaceutical research. Jun 25 2014.

Ito N, Seki S, Ueda F. The Protective Role of Astaxanthin for UV-Induced Skin Deterioration in Healthy People-A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. Jun 25 2018;10(7)doi:10.3390/nu10070817.

James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. The American journal of clinical nutrition. Jan 2000;71(1 Suppl):343s-348s.

Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science (New York, N.Y.). Jan 10 1997;275(5297):218-220.

Jensen JM, Forl M, Winoto-Morbach S, Seite S, Schunck M, Proksch E, Schutze S. Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging. Experimental dermatology. Aug 2005;14(8):609-618.

Jugdaohsingh R. Silicon and bone health. The journal of nutrition, health & aging. Mar-Apr 2007;11(2):99-110.

Juturu V, Bowman JP, Deshpande J. Overall skin tone and skin-lightening-improving effects with oral supplementation of lutein and zeaxanthin isomers: a double-blind, placebo-controlled clinical trial. Clin Cosmet Investig Dermatol. 2016;9:325-332. doi:10.2147/ccid.S115519.

Kadler KE, Baldock C, Bella J, Boot-Handford RP. Collagens at a glance. Journal of cell science. Jun 15 2007;120(Pt 12):1955-1958.

Kahan V, Andersen ML, Tomimori J, Tufik S. Can poor sleep affect skin integrity? Medical hypotheses. Dec 2010;75(6):535-537.

Kambayashi H, Yamashita M, Odake Y, Takada K, Funasaka Y, Ichihashi M. Epidermal changes caused by chronic low-dose UV irradiation induce wrinkle formation in hairless mouse. Journal of dermatological science. Aug 2001;27 Suppl 1:S19-25.

Katsuoka K, Mauch C, Schell H, Hornstein OP, Krieg T. Collagen-type synthesis in human-hair papilla cells in culture. Archives of Dermatological Research. 1988;280(3):140-144.

Katta R, Desai SP. Diet and dermatology: the role of dietary intervention in skin disease. The Journal of clinical and aesthetic dermatology. Jul 2014;7(7):46-51.

Kim DH, Je YJ, Kim CD, Lee YH, Seo YJ, Lee JH, Lee Y. Can Platelet-rich Plasma Be Used for Skin Rejuvenation? Evaluation of Effects of Platelet-rich Plasma on Human Dermal Fibroblast. Annals of dermatology. 2011;23(4):424-431.

Kim HH, Cho S, Lee S, Kim KH, Cho KH, Eun HC, Chung JH. Photoprotective and anti-skin-aging effects of eicosapentaenoic acid in human skin in vivo. Journal of lipid research. May 2006;47(5):921-930.

Kim HH, Shin CM, Park CH, Kim KH, Cho KH, Eun HC, Chung JH. Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts. Journal of lipid research. Aug 2005;46(8):1712-1720.

Kim JE, Shin MH, Chung JH. Epigallocatechin-3-gallate prevents heat shock-induced MMP-1 expression by inhibiting AP-1 activity in human dermal fibroblasts. Archives for dermatological research. Archiv fur dermatologische Forschung. Sep 2013;305(7):595-602.

Kim KH, Back JH, Zhu Y, et al. Resveratrol targets transforming growth factor-beta2 signaling to block UV-induced tumor progression. The Journal of investigative dermatology. Jan 2011;131(1):195-202.

Kim WS, Park BS, Park SH, Kim HK, Sung JH. Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors. J Dermatol Sci. Feb 2009;53(2):96-102.

Kligman AM. Guidelines for the use of topical tretinoin (Retin-A) for photoaged skin. Journal of the American Academy of Dermatology. Sep 1989;21(3 Pt 2):650-654.

Konda D, Thappa DM. Mesotherapy: What is new? Indian journal of dermatology, venereology and leprology. Jan-Feb 2013;79(1):127-134.

Koster MI. Making an epidermis. Annals of the New York Academy of Sciences. Jul 2009;1170:7-10.

Krueger N, Sadick NS. New-generation radiofrequency technology. Cutis. Jan 2013;91(1):39-46.

Lefevre M, Redman LM, Heilbronn LK, et al. Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis. Mar 2009;203(1):206-213.

Levinbook WS. Merck Manual. Consumer Version. Overview of Hair Growth. http://www.merckmanuals.com/home/skin-disorders/hair-disorders/overview-of-hair-growth. Copyright 2016. Accessed 9/13/2016.

Lijnen P, Petrov V. Transforming growth factor-beta 1-induced collagen production in cultures of cardiac fibroblasts is the result of the appearance of myofibroblasts. Methods and findings in experimental and clinical pharmacology. Jul-Aug 2002;24(6):333-344.

Lim HW, Wang SQ. The Skin Cancer Foundation's Guide to Suncreens. 7/3/2012. Accessed 5/2/2016.

Lipotec. Uplevity. http://www.lotioncrafter.com/reference/Uplevity_Tech_Data.pdf. 6/2013. Accessed 9/13/2016.

Lipozencic J, Bukvic-Mokos Z. Corrective dermatology today. Acta clinica Croatica. Dec 2010a;49(4):519-523.

Lipozencic J, Bukvic Mokos Z. Dermatologic lasers in the treatment of aging skin. Acta dermatovenerologica Croatica : ADC. 2010b;18(3):176-180.

Loesch MM, Somani AK, Kingsley MM, Travers JB, Spandau DF. Skin resurfacing procedures: new and emerging options. Clin Cosmet Investig Dermatol. 2014;7:231-241.

Louis A, Petereit F, Lechtenberg M, Deters A, Hensel A. Phytochemical characterization of Rhododendron ferrugineum and in vitro assessment of an aqueous extract on cell toxicity. Planta medica. Oct 2010;76(14):1550-1557.

Lu'o'ng KV, Nguyen LT. The role of vitamin D in Alzheimer's disease: possible genetic and cell signaling mechanisms. Am J Alzheimers Dis Other Demen. Mar 2013;28(2):126-136.

Lukes M, Prochazkova L, Shmidt V, Nedbalova L, Kaftan D. Temperature dependence of photosynthesis and thylakoid lipid composition in the red snow alga Chlamydomonas cf. nivalis (Chlorophyceae). FEMS microbiology ecology. Aug 2014;89(2):303-315.

Makrantonaki E, Schonknecht P, Hossini AM, et al. Skin and brain age together: The role of hormones in the ageing process. Experimental gerontology. Oct 2010;45(10):801-813.

Mammone T, Gan D, Goyarts E, Maes D. Salicylic acid protects the skin from UV damage. Journal of cosmetic science. Mar-Apr 2006;57(2):203-204.

Mandy SH. Tretinoin in the preoperative and postoperative management of dermabrasion. Journal of the American Academy of Dermatology. Oct 1986;15(4 Pt 2):878-879, 888-879.

Manna F, Dentini M, Desideri P, De Pita O, Mortilla E, Maras B. Comparative chemical evaluation of two commercially available derivatives of hyaluronic acid (hylaform from rooster combs and restylane from streptococcus) used for soft tissue augmentation. Journal of the European Academy of Dermatology and Venereology : JEADV. Nov 1999;13(3):183-192.

Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA : the journal of the American Medical Association. Oct 2013;310(13):1353-1368.

Margadant C, Charafeddine RA, Sonnenberg A. Unique and redundant functions of integrins in the epidermis. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. Nov 2010;24(11):4133-4152.

Martin KR. Silicon: the health benefits of a metalloid. Metal ions in life sciences. 2013;13:451-473.

Mayo Clinic. Diseases and Conditions: Wrinkles. Available at http://www.mayoclinic.org/diseases-conditions/wrinkles/basics/treatment/con-20029887?p=1. Last updated 10/21/2014. Accessed 07/27/2016.

McLafferty E, Hendry C, Alistair F. The integumentary system: anatomy, physiology and function of skin. Nursing standard (Royal College of Nursing (Great Britain): 1987). Sep 19-25 2012;27(3):35-42.

Metabiotics. Product monograph. Resveratrol. January 29, 2009.

Meyer TE, Kovacs SJ, Ehsani AA, Klein S, Holloszy JO, Fontana L. Long-term caloric restriction ameliorates the decline in diastolic function in humans. Journal of the American College of Cardiology. Jan 17 2006;47(2):398-402.

Michalak M, Pierzak M, Kręcisz B, Suliga E. Bioactive Compounds for Skin Health: A Review. Nutrients. Jan 12 2021;13(1)doi:10.3390/nu13010203.

Michan S. Calorie restriction and NAD(+)/sirtuin counteract the hallmarks of aging. Frontiers in bioscience (Landmark edition). 2014;19:1300-1319.

Michels AJ. Linus Pauling Institute. Micronutrient Information Center. Micronutrients and Skin Health. http://lpi.oregonstate.edu/mic/micronutrients-health/skin-health. 9/2011. Accessed 9/13/2016.

Miller AB, Breen M, Murphy KE. Chromosomal localization of acidic and basic keratin genes of the domestic dog. Mammalian genome: official journal of the International Mammalian Genome Society. Apr 1999;10(4):371-375.

Mizuno H, Tobita M, Uysal AC. Concise review: Adipose-derived stem cells as a novel tool for future regenerative medicine. Stem cells (Dayton, Ohio). May 2012;30(5):804-810.

Montemurro B, Gillen MM. Wrinkles and sagging flesh: exploring transformations in women's sexual body image. Journal of women & aging. 2013;25(1):3-23.

Morasso MI, Tomic-Canic M. Epidermal stem cells: the cradle of epidermal determination, differentiation and wound healing. Biology of the cell / under the auspices of the European Cell Biology Organization. Mar 2005;97(3):173-183.

Morini F, Dusatti F, Bonina FP, Saija A, Ferro M. Iron-induced Lipid Peroxidation in Human Skin-derived Cell Lines: Protection by a Red Orange Extract. Alternatives to laboratory animals: ATLA. May-Jun 2000;28(3):427-433.

Morita A. Tobacco smoke causes premature skin aging. J Dermatol Sci. Dec 2007;48(3):169-175.

Mostafa WZ, Hegazy RA. Vitamin D and the skin: Focus on a complex relationship: A review. Journal of advanced research. Nov 2015;6(6):793-804.

Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clinical interventions in aging. 2006;1(4):327-348.

Ndiaye M, Philippe C, Mukhtar H, Ahmad N. The grape antioxidant resveratrol for skin disorders: promise, prospects, and challenges. Archives of biochemistry and biophysics. Apr 15 2011;508(2):164-170.

Nestor MS, Berman B, Swenson N. Safety and Efficacy of Oral Polypodium leucotomos Extract in Healthy Adult Subjects. The Journal of clinical and aesthetic dermatology. Feb 2015;8(2):19-23.

NIH. National Cancer Institute. NCI Dictionary of Cancer Terms. Keratin http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=721317. Accessed 9/13/2016.

Niren NM. Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review. Cutis. Jan 2006;77(1 Suppl):11-16.

NLM. U.S. National Library of Medicine. Aging changes in hair and nails. https://www.nlm.nih.gov/medlineplus/ency/article/004005.htm. Last updated 8/23/2016a. Accessed 9/13/2016.

NLM. U.S. National Library of Medicine. Skin Aging. https://www.nlm.nih.gov/medlineplus/skinaging.html. Last updated 8/23/2016. Last updated 8/23/2016b. Accessed 9/13/2016.

Nouveau S, Bastien P, Baldo F, de Lacharriere O. Effects of topical DHEA on aging skin: a pilot study. Maturitas. Feb 20 2008;59(2):174-181.

Okawa T, Yamaguchi Y, Takada S, et al. Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model. J Dermatol Sci. May 2012;66(2):136-143.

OPT. Oldways Preservation Trust. Traditional Med Diet. http://oldwayspt.org/resources/heritage-pyramids/mediterranean-diet-pyramid/traditional-med-diet. Accessed 4/26/2016

Ortonne JP. Pigmentary changes of the ageing skin. Br J Dermatol. Apr 1990;122 Suppl 35:21-28.

Oyetakin-White P, Suggs A, Koo B, Matsui MS, Yarosh D, Cooper KD, Baron ED. Does poor sleep quality affect skin ageing? Clinical and experimental dermatology. Jan 2015;40(1):17-22.

Pageon H. Reaction of glycation and human skin: the effects on the skin and its components, reconstructed skin as a model. Pathologie-biologie. Jun 2010;58(3):226-231.

Pageon H, Zucchi H, Rousset F, Monnier VM, Asselineau D. Skin aging by glycation: lessons from the reconstructed skin model. Clinical chemistry and laboratory medicine : CCLM / FESCC. Jan 1 2014;52(1):169-174.

Pak C, Park J, Hong J, Jeong J, Bang S, Heo CY. A Phase III, Randomized, Multi-Center, Double-Masked, Matched-Pairs, Active-Controlled Trial to Compare the Efficacy and Safety between Neuramis Deep and Restylane in the Correction of Nasolabial Folds. Archives of plastic surgery. Nov 2015;42(6):721-728.

Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? The Journal of steroid biochemistry and molecular biology. Oct 2014;144 Pt A:138-145.

Pandel R, Poljšak B, Godic A, Dahmane R. Skin Photoaging and the Role of Antioxidants in Its Prevention. ISRN Dermatology. 2013;2013:930164.

Park BS, Jang KA, Sung JH, Park JS, Kwon YH, Kim KJ, Kim WS. Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. Oct 2008;34(10):1323-1326.

Pavicic T, Gauglitz GG, Lersch P, Schwach-Abdellaoui K, Malle B, Korting HC, Farwick M. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. Journal of drugs in dermatology: JDD. Sep 2011;10(9):990-1000.

Pei XR, Yang RY, Zhang ZF, Xu YJ, Han XL, Wang JB, Li Y. [Effects of marine collagen peptide on delaying the skin aging]. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]. Apr 2008;42(4):235-238.

Peng Y, Reyes JL, Wei H, et al. RcDhn5, a cold acclimation-responsive dehydrin from Rhododendron catawbiense rescues enzyme activity from dehydration effects in vitro and enhances freezing tolerance in RcDhn5-overexpressing Arabidopsis plants. Physiologia plantarum. Dec 2008;134(4):583-597.

Philips N, Conte J, Chen YJ, et al. Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells. Archives for dermatological research. Archiv fur dermatologische Forschung. Aug 2009;301(7):487-495.

Phillips TJ, Demircay Z, Sahu M. Hormonal effects on skin aging. Clin Geriatr Med. Nov 2001;17(4):661-672, vi.

PhytoCellTec. PhytoCellTec Alp Rose. http://www.phytocelltec.ch/pctalprose.php?l=en. Copyright 2010. Accessed 9/13/2016.

Piccardi N, Manissier P. Nutrition and nutritional supplementation: Impact on skin health and beauty. Dermato-endocrinology. Sep 2009;1(5):271-274.

Pilkington SM, Massey KA, Bennett SP, et al. Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses. The American journal of clinical nutrition. Mar 2013;97(3):646-652.

Prentice RL. Postmenopausal Hormone Therapy and the Risks of Coronary Heart Disease, Breast Cancer, and Stroke. Seminars in reproductive medicine. 2014;32(6):419-425.

Prikhnenko S. Polycomponent mesotherapy formulations for the treatment of skin aging and improvement of skin quality. Clin Cosmet Investig Dermatol. 2015;8:151-157.

Proksch E, Schunck M, Zague V, Segger D, Degwert J, Oesser S. Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis. Skin Pharmacol Physiol. 2014;27(3):113-119.

Proksch E, Segger D, Degwert J, Schunck M, Zague V, Oesser S. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Skin Pharmacol Physiol. 2014;27(1):47-55.

Puglia C, Offerta A, Saija A, Trombetta D, Venera C. Protective effect of red orange extract supplementation against UV-induced skin damages: photoaging and solar lentigines. Journal of cosmetic dermatology. Jun 2014;13(2):151-157.

Puizina-Ivic N, Miric L, Carija A, Karlica D, Marasovic D. Modern approach to topical treatment of aging skin. Collegium antropologicum. Sep 2010;34(3):1145-1153.

Purdue University. Food Chemistry 45300. Gelatin. [Powerpoint Presentation]. http://www.cfs.purdue.edu/FN/fn453/pdf_full/gelatin_2.pdf. Accessed 5/9/2016

Pyun HB, Kim M, Park J, et al. Effects of Collagen Tripeptide Supplement on Photoaging and Epidermal Skin Barrier in UVB-exposed Hairless Mice. Preventive nutrition and food science. Dec 2012;17(4):245-253.

Quan T, Qin Z, Xia W, Shao Y, Voorhees JJ, Fisher GJ. Matrix-degrading metalloproteinases in photoaging. The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. Aug 2009;14(1):20-24.

Quan T, Shao Y, He T, Voorhees JJ, Fisher GJ. Reduced expression of connective tissue growth factor (CTGF/CCN2) mediates collagen loss in chronologically aged human skin. The Journal of investigative dermatology. Feb 2010;130(2):415-424.

Rabionet M, Gorgas K, Sandhoff R. Ceramide synthesis in the epidermis. Biochimica et biophysica acta. Mar 2014;1841(3):422-434.

Raschke T, Koop U, Dusing HJ, et al. Topical activity of ascorbic acid: from in vitro optimization to in vivo efficacy. Skin Pharmacol Physiol. Jul-Aug 2004;17(4):200-206.

Ravussin E, Redman LM, Rochon J, et al. A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. The journals of gerontology. Series A, Biological sciences and medical sciences. Sep 2015;70(9):1097-1104.

Reichrath J. Unravelling of hidden secrets: The role of vitamin D in skin aging. Dermato-endocrinology. Jul 1 2012;4(3):241-244.

Rhie G, Shin MH, Seo JY, et al. Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo. The Journal of investigative dermatology. Nov 2001;117(5):1212-1217.

Riso P, Visioli F, Grande S, et al. Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress. J Agric Food Chem. 2006;54(7):2563-2566.

Rizwan M, Rodriguez-Blanco I, Harbottle A, et al. Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial. Br J Dermatol.


Rizza W, Veronese N, Fontana L. What are the roles of calorie restriction and diet quality in promoting healthy longevity? Ageing Res Rev. Jan 2014;13:38-45.

Rosenberg S, OSTER KA, KALLOS A, BURROUGHS W. Further studies in the use of gelatin in the treatment of brittle nails. AMA archives of dermatology. 1957;76(3):330-335.

Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA: the journal of the American Medical Association. Jul 2002;288(3):321-333.

Saewan N, Jimtaisong A. Natural products as photoprotection. Journal of cosmetic dermatology. Mar 2015;14(1):47-63.

Sage RJ, Lim HW. Therapeutic Hotline: Recommendations on photoprotection and vitamin D. Dermatologic therapy. Jan-Feb 2010;23(1):82-85.

Saito S, Katoh M, Masumoto M, Matsumoto S, Masuho Y. Involvement of MMP-1 and MMP-3 in collagen degradation induced by IL-1 in rabbit cartilage explant culture. Life sciences. 1998;62(22):Pl 359-365.

Samaras N, Samaras D, Forster A, Frangos E, Philippe J. [Age related dehydroepiandrosterone decrease: clinical significance and therapeutic interest]. Revue medicale suisse. Jan 28


Sanguineti R, Puddu A, Mach F, Montecucco F, Viviani GL. Advanced glycation end products play adverse proinflammatory activities in osteoporosis. Mediators of inflammation. 2014;2014:975872.

Sator PG, Schmidt JB, Rabe T, Zouboulis CC. Skin aging and sex hormones in women -- clinical perspectives for intervention by hormone replacement therapy. Experimental dermatology. 2004;13 Suppl 4:36-40.

Sauermann K, Jaspers S, Koop U, Wenck H. Topically applied vitamin C increases the density of dermal papillae in aged human skin. BMC dermatology. Sep 29 2004;4(1):13.

Savoia A, Landi S, Baldi A. A new minimally invasive mesotherapy technique for facial rejuvenation. Dermatology and therapy. Jun 2013;3(1):83-93.

Saxon SV, Etten MJ, Perkins EA, Ebooks C. Physical change & aging: a guide for the helping professions. Vol 5th. New York: Springer Publishing Company; 2010.

Schagen SK, Zampeli VA, Makrantonaki E, Zouboulis CC. Discovering the link between nutrition and skin aging. Dermatoendocrinol. Jul 1 2012;4(3):298-307.

Scheinfeld N, Dahdah MJ, Scher R. Vitamins and minerals: their role in nail health and disease. Journal of drugs in dermatology : JDD. Aug 2007;6(8):782-787.

Schmidt JB, Binder M, Demschik G, Bieglmayer C, Reiner A. TREATMENT OF SKIN AGING WITH TOPICAL ESTROGENS. International journal of dermatology. 1996;35(9):669-674.

Schwimmer M, Mulinos M. Salutary effects of gelatin on nail defects in normal subjects. Plastic and reconstructive surgery. 1957;20(5):415-416.

Seaborn CD NF. Silicon: a nutritional beneficence fro bones, brains, and blood vessels? Nutrition Today. July/August1993.

Seaborn CD, Nielsen FH. Silicon deprivation decreases collagen formation in wounds and bone, and ornithine transaminase enzyme activity in liver. Biological trace element research. Dec 2002;89(3):251-261.

Sederma. New Products. Matrixyl synthe' 6. http://www.sederma.com/home.aspx?s=111&r=127&p=1414. Copyright 2016. Accessed 9/13/2016.

Sheth H, Sheth J, Sheth F, Burn J. The poor patient with diabetes 'should live like a saint'. Diabetic medicine : a journal of the British Diabetic Association. Jun 4 2015.

Shin MH, Rhie GE, Park CH, Kim KH, Cho KH, Eun HC, Chung JH. Modulation of collagen metabolism by the topical application of dehydroepiandrosterone to human skin. The Journal of investigative dermatology. Feb 2005;124(2):315-323.

Simmons BJ, Griffith RD, Falto-Aizpurua LA, Nouri K. Use of radiofrequency in cosmetic dermatology: focus on nonablative treatment of acne scars. Clin Cosmet Investig Dermatol. 2014;7:335-339.

Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end products and diabetic complications. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology. Feb 2014;18(1):1-14.

Skjot-Arkil H, Clausen RE, Nguyen QH, et al. Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation. BMC pulmonary medicine. 2012;12:34.

Slonim AE, Sadick N, Pugliese M, Meyers-Seifer CH. Clinical response of alopecia, trichorrhexis nodosa, and dry, scaly skin to zinc supplementation. J Pediatr. Dec 1992;121(6):890-895.

Small R. Botulinum toxin injection for facial wrinkles. American family physician. Aug 1 2014;90(3):168-175.

Snow-Algae. Proven Efficacy. AMPK Activation. http://www.snow-algae.com/efficacy/ampk-activation.html. Copyright 2014a. Accessed 9/13/2016..

Snow-Algae. Proven Efficacy. Klotho, a Gene for Longevity. http://www.snow-algae.com/efficacy/stimulation-of-klotho.html. Copyright 2014b. Accessed 9/13/2016.

Snow-Algae. Proven Efficacy. Strong Skin Barrier. http://www.snow-algae.com/efficacy/strong-skin-barrier.html. Copyright 2014c. Accessed 9/13/2016.

Sonnichsen N, Reinicke C, Herrmann C, Glatzel E. [Zinc therapy of alopecia areata]. Dermatologische Monatschrift. 1984;170(7):437-442.

Sonti S, Makino ET, Garruto JA, Gruber JV, Rao S, Mehta RC. Efficacy of a novel treatment serum in the improvement of photodamaged skin. Int J Cosmet Sci. Apr 2013;35(2):156-162.

Stein PK, Soare A, Meyer TE, Cangemi R, Holloszy JO, Fontana L. Caloric restriction may reverse age-related autonomic decline in humans. Aging Cell. Aug 2012;11(4):644-650.

Steven S, Taylor R. Restoring normoglycaemia by use of a very low calorie diet in long- and short-duration Type 2 diabetes. Diabetic medicine : a journal of the British Diabetic Association. Sep 2015;32(9):1149-1155.

Sudha PN, Rose MH. Beneficial effects of hyaluronic acid. Advances in food and nutrition research. 2014;72:137-176.

Suman T. Enhancing facial esthetics by other modalities. International journal of dentistry. 2011;2011:513957.

Surette ME. The science behind dietary omega-3 fatty acids. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. Jan 15 2008;178(2):177-180.

Surjana D, Halliday GM, Martin AJ, Moloney FJ, Damian DL. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. The Journal of investigative dermatology. May 2012;132(5):1497-1500.

Tarshish E, Hermoni K. Beauty from within: Improvement of skin health and appearance with Lycomato a tomato-derived oral supplement. Journal of cosmetic dermatology. Jun 2023;22(6):1786-1798. doi:10.1111/jocd.15650.

Ting W. Tretinoin for the treatment of photodamaged skin. Cutis. Jul 2010;86(1):47-52.

Traikovich SS. Use of topical ascorbic acid and its effects on photodamaged skin topography. Archives of otolaryngology--head & neck surgery. Oct 1999;125(10):1091-1098.

Trookman NS, Rizer RL, Ford R, Ho E, Gotz V. Immediate and Long-term Clinical Benefits of a Topical Treatment for Facial Lines and Wrinkles. The Journal of clinical and aesthetic dermatology. Mar 2009;2(3):38-43.

Trüeb RM. Pharmacologic interventions in aging hair. Clinical interventions in aging. 06/2006;1(2):121-129.

Uitto J. The role of elastin and collagen in cutaneous aging: intrinsic aging versus photoexposure. Journal of drugs in dermatology : JDD. Feb 2008;7(2 Suppl):s12-16.

UMMC. University of Maryland Medical Center. Facial Plastic Surgery. Factors Affecting Our Skin. http://umm.edu/programs/facial-plastic/health/skin-care-tips/factors-affecting-our-skin. Copyright 2016. Accessed 9/13/2016.

Urbanska M, Nowak G, Florek E. [Cigarette smoking and its influence on skin aging]. Przeglad lekarski. 2012;69(10):1111-1114.

Vantage. Vantage Specialty Ingredients. Hylasome EG-10 http://www.lipochemicals.com/products/hylasome-eg-10. Accessed 9/13/2016.

Vierkotter A, Schikowski T, Ranft U, Sugiri D, Matsui M, Kramer U, Krutmann J. Airborne particle exposure and extrinsic skin aging. The Journal of investigative dermatology. Dec 2010;130(12):2719-2726.

Wang Y, Zuo M. Nicotinamide improves sevoflurane-induced cognitive impairment through suppression of inflammation and anti-apoptosis in rat. International journal of clinical and experimental medicine. 2015;8(11):20079-20085.

Wing RR, Blair EH, Bononi P, Marcus MD, Watanabe R, Bergman RN. Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes care. Jan 1994;17(1):30-36.

Winkelmann RR, Del Rosso J, Rigel DS. Polypodium leucotomos extract: a status report on clinical efficacy and safety. Journal of drugs in dermatology: JDD. Mar 2015;14(3):254-261.

Wolowa F, Stachow A. [Zinc sulfate in the treatment of alopecia areata]. Przeglad dermatologiczny. Nov-Dec 1978;65(6):687-696.

Yiasemides E, Sivapirabu G, Halliday GM, Park J, Damian DL. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis. Jan 2009;30(1):101-105.

Yuksel EP, Sahin G, Aydin F, Senturk N, Turanli AY. Evaluation of effects of platelet-rich plasma on human facial skin. Journal of cosmetic and laser therapy: official publication of the European Society for Laser Dermatology. Oct 2014;16(5):206-208.

Yusuf N, Irby C, Katiyar SK, Elmets CA. Photoprotective effects of green tea polyphenols. Photodermatology, photoimmunology & photomedicine. Feb 2007;23(1):48-56.

Zhang S, Dong Z, Peng Z, Lu F. Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose. PloS one. 2014;9(5):e97573.

Zhou X, Cao Q, Orfila C, Zhao J, Zhang L. Systematic Review and Meta-Analysis on the Effects of Astaxanthin on Human Skin Ageing. Nutrients. Aug 24 2021;13(9)doi:10.3390/nu13092917.

Zouboulis CC, Adjaye J, Akamatsu H, Moe-Behrens G, Niemann C. Human skin stem cells and the ageing process. Experimental gerontology. Nov 2008;43(11):986-997.