Group:Skin and Aging

Your skin changes as you age. Skin aging (or aging in general) is a complex process driven by both genetic and environmental factors. According to a recent JAMA study, 60% of our ageing is based on our genes while only 40% is determined by the environment. Some people are exceptional agers; their skin does not change much over decades while others develop wrinkles earlier in life. Many factors can contribute to this process; but, most importantly, increased collagen breakdown and the glycation process are culprits. Similarly, sagging eyelids can become a frequent concern in some middle-aged and older adults. In this section, explore how your genetic makeup impacts your skin as you age and what actions you could take to facilitate this process.

Sagging Eyelids Risk

Code:SkinSaggingEyelids2Use

Connotation:risky

Sagging eyelids (hooded eyes or dermatochalasis) are a frequent concern in middle-aged and older adults. It happens due to a loss of elastic fibers and a disruption of the collagen network. Sagging eyelids are usually a cosmetic concern, although they can cause visual field loss, ocular or eyelid irritation. They may also be a cause of headaches due to forced brow elevation to increase the visual field. A recent study identified nearly 30 genetic variations associated with sagging eyelids. These variations are located in 6 different genetic regions that contain four genes TGIF1, SMYD3, ATP8A1, and PJA2. Interestingly, some of the identified genetic variations, including variation in the TGIF1 gene (an inducer of transforming growth factor β) have protective effects while others are associated with increased incidents of sagging eyelids.

Skin Glycation

Code:SkinGlycation

Connotation:risky

Our bodies use glucose as its main source of fuel. If glucose is not metabolized properly, it can bind to skin’s collagen and elastin fibers forming abnormal cross-links. This leads to structural and functional tissue impairment which produces advanced glycation products (AGEs). This process, called glycation, is responsible in accelerated aging of the skin as it impairs skin’s ability to regenerate and self-repair. Glycation has been described as caramelization (hardening) of the skin from the inside out. The skin-damaging effects of glycation cause wrinkles, dryness, skin laxity. Scientific research identified several genetic variations in NAT2, GLO1, and AGER genes are associated with excessive glycation. A recent study found that the presence of slow NAT2 acetylator types correlates with higher levels of AGEs in their skin. Genetic variations in the glyoxalase 1 enzyme (GLO1) that protects cells from AGEs can lower their activity which leads to the build-up of AGEs. Another gene implicated in glycation and skin aging is AGER receptor. Binding of AGEs to AGER results in activation of collagen breakdown enzymes and the pro-inflammatory cytokines. In simpler terms, it leads to the breakdown of collagen in the skin prompting wrinkles and other complexities.

Collagen Breakdown

Code:SkinCollagenBreakdown

Connotation:risky

Collagen is a connective tissue protein that makes up around a quarter of all the protein found in the body. It helps support and strengthen bones, teeth, tendons, skin, and internal organs. In particular, it affects your skin elasticity. Skin elasticity is the skin's ability to stretch and revert to its original form without developing wrinkles and imperfections. It is determined by collagen that makes up to 75% of our skin. The smoothness, firmness, and elasticity of the skin depend on the balance between collagen synthesis and its breakdown. Levels of MMPs increase in the course of normal aging and exposure to environmental factors (UV radiation) and irritation. In addition, genetic variants also increase activity of MMPs contributing to accelerated loss of collagen and premature skin aging.

Youthfulness

Code:SkinYouthfulness

Connotation:good

The research into genetics for younger looking skin has recently yielded results showing several genetic variations. Individuals with these genetic variations look years younger and their facial skin showed fewer signs of aging. These genes are not only important for outward appearance but are also necessary to study general anti-aging and longevity.

Group:Skin and the Environment

The health of your skin is determined by two factors: the environment and genetics. While many skin problems are caused by irritants and chemicals in the air (such as automobile exhaust, allergens, and industrial smoke), variants in the genes also play a key role in skin protection, barrier function, and detoxification. Hence, our skin maintains a sophisticated system to defend itself from both internal and external toxins. In this section, explore how your genetic makeup affects your skin's sensitivity to environmental factors, and use this knowledge to be  more proactive about protecting your skin.

Skin Detoxification Impairment

Code:SkinDetoxification

Connotation:risky

Human skin maintains a sophisticated detoxification system by converting environmental toxins and reactive oxygen species (ROS) into water-soluble forms ( by a mechanism called conjugation) and pairing these products with glutathione. Glutathione is a master detoxifier produced naturally by the liver. It is also found in fruits, vegetables, and meats. Glutathione also plays a critical role in maintaining optimal levels of vitamins C and E. Genetic variations in several enzymes can lower glutathione activity compromising its detoxification capacity which then results in the accumulation of ROS. Insufficient ROS detoxification may result in cellular damage, and may contribute to skin inflammation and premature aging. This also increases the individual's susceptibility to environmental toxins (automobile emissions, allergens, and cigarette smoke)

Dermal Sensitivity

Code:SkinDermalSensitivity

Connotation:risky

Skin sensitivity is largely determined by the skin barrier function ; this  determines skin permeability and the prevention of the entry of harmful pathogens and toxins. In addition, a hyper-reactive immune response to allergens and deficiency in protection from environmental toxins can both contribute to overall skin sensitivity risk. In some cases, dermal sensitivity leads to atopic dermatitis, or eczema, which is in fact one of the most common skin conditions (with prevalence rates of up to 20% in children and 3% in adults in the developed world). Eczema is characterized by very dry skin, and a typical age-related distribution of inflammatory lesions that are frequently infected by bacteria and viruses. It is important to consult a dermatologist if you experience any of these symptoms. Your overall dermal sensitivity risk has been calculated using the results from a large genome-wide study where a number of genetic variants associated with increased risk of skin sensitivity were identified.

Pollution Defense Impairment

Code:SkinPollutionDefense

Connotation:risky

Air pollution is the cause of increased signs of aging, dark spots, and inflammation. The Chinese Dermatologist Association has found that those living in highly polluted areas (i.e. big cities) age 10 times faster than those who live in the countryside. Two important enzymes, EPHX1 and NQO1, protect our bodies  from systemic absorption of highly reactive foreign chemicals (epoxides and quinones) from within the epidermis (most superficial layer of our skin). Biotransformation enzyme, EPHX1, plays a critical part in preventing the  absorption of epoxides by catalyzing them into a less reactive, water-soluble form. Similarly, NQO1 converts coenzyme Q10 (ubiquinone) to its reduced form, ubiquinol, which then scavenges free radicals in the mitochondria and skin lipid membrane. Genetic variants in the EPHX1 gene cause epoxide hydrolase deficiency while SNPs in the NQO1 gene slow down production of ubiquinol. Individuals who have reduced levels of these two enzymes have significantly diminished skin defense from environmental toxins.

Contact Skin Sensitivity

Code:AllergicDermatitis

Connotation:risky

Contact skin sensitivities (contact allergy) are becoming more prevalent around the world. One of the most common types is the allergic reaction to nickel or other metals.The rise of contact allergy can be due to increased exposure to nickel in the environment as it is found in everyday items (jewelry, belt buckles, watch straps, metal zips, bra hooks, buttons, pocket knives, lipstick holders etc). Recent studies have identified genetic variations which are associated with the presence of nickel and other metal sensitivity.

Skin Barrier Sensitivity

Code:SkinBarrierSensitivity

Connotation:risky

Our skin barrier serves a crucial, protective function for the skin by preventing entry of harmful microbes, toxins, and allergens while maintaining proper skin hydration. Skin barrier function is performed primarily in the outermost layer of the epidermis called the Stratum Corneum (SC). Stratum Corneum is also responsible for thermoregulation and innate immunity. Genetic variations in the Flaggirin (FLG) gene may cause skin barrier defects increasing its permeability and promoting skin sensitivity and irritation. In more extreme cases, genetic variations in the FLG gene are also associated with eczema and allergies. In up to 10% persons of European ancestry, parts of the FLG gene are deleted. As a result, this has strongly predisposed those people to eczema, asthma, and other severe allergies.Variations in the FLG gene may be the cause of sensitive or hypersensitive skin. People with a sensitive skin barrier are also three times more likely to suffer from a peanut allergy.

Group:Skin and the Sun

The sun plays an integral part in our well being and we draw our energy from it in various ways. One such example is when your skin synthesizes sunlight to help manufacture Vitamin D. This vitamin is crucial for normal bone functioning and many other processes. While sunlight is life-giving, ultraviolet light (also found in sunlight) is detrimental and can age unprotected skin faster. Humans vary over 1000-fold in their sensitivity to the effects of ultraviolet radiation which is largely determined by their genetics. Skin pigmentation, tanning ability, and sensitivity to sun have high heritability. People with lighter skin tones can be susceptible to painful sunburns from being exposed to the sun for prolonged periods of time. Similarly, people with darker skin tones or those who tan well mistakenly assume that the sun may not impact them negatively. But, in reality, there are other adverse reactions that their skin may be experiencing which are not visible to the naked eye. In this section, you can gain insight on how your genetic makeup influences how your skin is impacted by sun exposure and the necessary measures you can take to limit further damage.

Facial Pigmented Spots

Code:SkinPigmentedSpots2Use

Connotation:risky

Facial pigmented spots (solar lentigines and seborrheic keratosis) are a common feature of aging skin and are usually a result of sun exposure. With age, the repeated UV exposure causes melanin, a compound responsible for pigmentation as well as protecting the skin, to cluster or clump together. These clumps form an area of hyperpigmentation.Pigmented age spots develop earlier and are more pronounced in Asian than in Caucasian skin (as a result of SLC45A2). While there are some similarities in manifestation of pigmented spots in different populations (determined by the MC1R, ASIP, IRF4, BNC2 genes), there are also ethnic differences.

Photoaging

Code:SkinPhotoaging

Connotation:risky

Skin photoaging is defined as premature aging of the skin due to sun exposure (UV radiation). UV radiation causes DNA damage, oxidative stress, and disrupts normal architecture of skin connective tissue that impairs skin function. Clinical data suggests that extrinsic skin aging parameters have a strong genetic basis. Studies have identified genetic variations in STXBP5L and FBXO40 genes. This was determined by careful analysis of age, smoking history, hormonal status, body-mass index, hair color at age 20,estimated sun exposure, and intensity. Another recent study also found that the MC1R gene, which is responsible for producing pale skin and red hair, is also linked to the susceptibility for increased photoaging.

Poor Tanning Ability

Code:SkinTanning

Connotation:risky

Tanning is the physiologically stimulated response to ultraviolet (UV) radiation in sunlight. UV exposure increases the production of eumelanin(one of the types of melanin) that darkens the skin in an attempt to protect it from damage. Ability of skin to tan is variable and is determined by genetics. Many genes are involved in the production of melanin which is the substance that gives skin, hair, and eyes their color. Large studies identified a number of genetic variants in the key pigmentation genes that are associated with tanning phenotype. Variants in the tyrosinase (TYR) gene encode skin color. MC1R gene is strongly associated with red hair, freckling and sun sensitivity: nearly all people with red hair have genetic variants in the MC1R gene, and hence diminished ability to tan. Similarly, genetic variants of OCA2 gene are responsible for the production of light colored eyes and light skin tones in East Asia. People with a number of genetic variants in the pigmentary genes tend to have lighter eye color, fair skin, and diminished ability to tan.

Sensitivity to Sun

Code:SkinSensitivity2Sun4Use

Connotation:risky

Humans vary over 1000-fold in their sensitivity to the harmful effects of ultraviolet radiation. Skin pigmentation, tanning ability and sensitivity to sun have high heritability. Several large-scale studies identified genetic variations that affect our skin sensitivity and tendency to get sun burns. The main determinants of sensitivity to sun are skin pigmentation genes (ASIP, TYR, MC1R, and OCA2) that are also associated with poor tanning. In addition, skin DNA repair genes are strongly associated with tendency to sun burns, and increased risk of melanoma. Interestingly, the DNA repair genes (NTM, ERCC1) have no association in either direction with tanning ability. This implies that there is a pigmentation-independent mechanism underlying sunburn reaction.

Group:Skin Profile

While environment, diet, stress, age, and hormones contribute to how your skin looks and feels, genetics also play a large role. They are important in determining whether your skin is inherently dry,  prone to acne, rosacea, or stretch marks. Genetic variants in some key enzymes may impact skin’s antioxidant capacity or inflammation. In this section, explore various skin care characteristics and learn how to choose the best skin care products for your unique skin needs.

Skin Stretch Marks

Code:SkinStretchMarksAll

Connotation:risky

Both men and women are prone to  stretch marks (striae, singular stria or striae distensae) on several parts of their bodies, including the belly, thighs, hips, breasts, upper arms, and lower back. Stretch marks are a form of scarring on the skin: the marks often start off with a reddish hue and as they progress, take an off-color appearance. Stretch marks are often the result of the rapid stretching of the skin dermis associated with rapid growth, weight changes, pregnancy (usually during the last trimester) or hormonal changes associated with puberty, bodybuilding, or hormone replacement therapy. Recent study identified several genetic variants in elastin gene (ELN) that are significantly associated with stretch marks.

Skin Rosacea

Code:SkinRosacea

Connotation:risky

Rosacea is a common but often overlooked chronic skin condition. According to the US National Rosacea Association,  well over 16 million Americans may have rosacea and aren’t aware. Rosacea cannot be cured, but it can be controlled. It is a chronic and potentially life-disrupting disorder of the facial skin, often characterized by flare-ups and remissions. Individuals with fair skin who tend to flush or blush easily are believed to be at greatest risk of rosacea but it can affect all segments of the population. Many causes of rosacea have been proposed: from excess alcohol consumption (especially red wine), sun exposure,  skin surface microbes, and small intestinal bacterial overgrowth. Some people report that spicy foods, hot baths, and emotional stress trigger rosacea symptoms. Genetics is a big factor in developing rosacea. A large study has recently identified several genetic variations significantly associated with rosacea. Interestingly, these variations have links to allergies and other autoimmune diseases as well.

Protection from Skin Cellulite

Code:SkinCellulite

Connotation:good

Cellulite is a condition when skin on thighs, hips, buttocks, and abdomen appears lumpy because of excess of fat beneath the skin. It is most common in women than men and even thin people are prone to it.There are many causes of cellulite including excessive weight, total body fat, poor diet, fad dieting, lack of physical activity, dehydration, hormone changes, and genetic predisposition. A small study of 200 lean women with cellulite and 200 BMI-matched controls identified two variations in ACE and HIF1A genes that were significantly associated with appearance of cellulite. Many treatments for cellulite, include massages, cellulite creams, lasers, and injections.Most of these treatments can work only in combination with a healthy, active lifestyle.

Acne

Code:SkinAcne

Connotation:risky

Acne (acne vulgaris) is most common in teenagers and young adults. It may also occur in adult women and men signaling hormonal imbalances. There are up to 3 million cases a year in the US. Of those affected, moderate to severe problems occur in 20%. Acne happens when hair follicles become clogged with dead skin cells and oil from the skin. Symptoms range from un-inflamed blackheads to pus-filled pimples or large, red, and tender bumps. In addition to hormonal changes and stress, genetics also contributes to the likelihood of acne.

Dryness

Code:SkinDryness

Connotation:risky

Balanced levels of hydration is absolutely fundamental for healthy skin. Aquaporin channels, a family of integral cell membrane proteins, play central role in keeping our skin hydrated by allowing the movement of water and glycerol across the cell membrane. The quality of aquaporin channels in human skin is strongly affected by aging, chronic sun exposure, and inflammation. The most abundant (and best studied) aquaporin in the skin is the AQP3 gene. It transports water, glycerol, and small solutes (urea) across the plasma membrane hence regulating skin hydration, skin barrier recovery, and wound healing. Another group of genes expressed in skin are called claudins. They are tight junction membrane proteins that form paracellular barriers and pores that determine tight junction permeability. Genetic variations in the AQP3 and CLDN1 genes can result in their diminished expression and reduced activity. This, in the epidermis, leads to impairments in skin intrinsic hydration capacity and skin dryness.

Skin Antioxidant Deficiency

Code:SkinAntioxidant

Connotation:risky

A balance between free radicals and intrinsic antioxidants is necessary for proper physiological functioning as well as to maintain youthful and healthy skin. Increased amounts of free radicals contribute to a dangerous chain of reactions that target tissues and organs in the body, including skin. This can  trigger many chronic and late-onset diseases while also leading to premature aging by damaging the skin’s proteins and lipids. To prevent such an occurrence, a master regulator gene, NRF2 (NF-E2-Related Factor 2), prompts the activation of SOD2/CAT(enzyme/protein) when it is triggered by oxidative stress and electrophiles. These enzymes convert free radicals into less harmful products. Genetic variations in NRF2, SOD2, and CAT can result in reduced antioxidant activities which then increases risk of damage to the skin’s lipids and proteins.

Skin Inflammation

Code:SkinInflammation

Connotation:risky

Skin inflammation is the result of a complex biological process where the cells in the skin have a hyperactive response to allergens or toxins and produce inflammatory hormones called cytokines and chemokines. There are two types of inflammation: acute and chronic. Acute inflammation is a signal to the skin to start the repair process after being exposed to triggering stimulus, such as germs or environmental toxins. It usually lasts 2-4 days (generally the amount of time required for wounds or infections to heal).When an inflammation is chronic and serves no purpose, it becomes destructive and can damage the skin. There are a number of stimuli that induce chronic inflammation: overexposure to UV rays, stress, toxins(e.g.pollution,smoking,trauma,alcohol,immune reactions,infections etc), pathogens, and foreign bodies( dirt and debris). Chronic inflammation plays an important role in overall skin sensitivity, and susceptibility to wound infection. It can also be triggered by excess of free radicals. In addition, genetic variations in several pro-inflammatory and anti-inflammatory cytokines genes are associated with higher risks of chronic skin inflammation.