A wrinkle is a fold, ridge or crease in the skin. Skin wrinkles typically appear as a result of aging processes such as glycation or, temporarily, as the result of prolonged (more than a few minutes) immersion in water. Wrinkling in the skin is caused by habitual facial expressions, aging, sun damage, smoking, poor hydration, and various other factors.[1] With prolonged water exposure, the outer layer of skin starts to absorb water. The skin doesn't expand evenly, causing it to wrinkle. Depletion of water in the body, as occurs with dehydration, can also cause this puckering of the skin.[2] Cortisol causes degradation of skin collagen.[3]
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Although the exact mode of action of tretinoin is unknown, current evidence suggests that tretinoin decreases cohesiveness of follicular epithelial cells. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells.[4] Tretinoin is better known by the brand name Retin-A.
Epidermal Growth Factor (EGF) is a small polypeptide of 53 amino acids and is a cytokine or cell messenger protein that stimulates epithelial cell proliferation. The discovery of EGF won Dr. Stanley Cohen a Nobel Prize in Physiology and Medicine in 1986. Taken internally, it is used to treat some devastating conditions of premature infants, as well as enlarged prostate in adult males. In cream form it stimulates cell renewal but decreases collagen production in the skin.[5] It is also helpful for wound and burn healing and has achieved amazing cures of severe ulcerating skin diseases such as life-threatening Steven-Johnson Syndrome (SJS).[6]
Glycosaminoglycans (GAGs) are produced by the body to maintain structural integrity in tissues and to maintain fluid balance. Hyaluronic acid is a type of GAG that promotes collagen synthesis, repair, and hydration. GAGs serve as a natural moisturizer and lubricant between epidermal cells to inhibit the production of matrix metalloproteinases (MMPs). Topical glycosaminoglycans supplements can help to provide temporary restoration of enzyme balance to slow or prevent matrix breakdown and consequent onset of wrinkle formation.[7]
Dermal fillers are injectable products frequently used to correct wrinkles, and other depressions in the skin. They are often a kind of soft tissue designed to enable injection into the skin for purposes of improving the appearance. The most common products are based on hyaluronic acid and calcium hydroxylapatite.
Botulinum toxin is a neurotoxin protein produced by the bacterium Clostridium botulinum. BOTOX (onabotulinumtoxinA) is a specific form of botulinum toxin manufactured by Allergan Inc (U.S.) for both therapeutic as well as cosmetic use. Besides its cosmetic application, BOTOX is used in the treatment of other conditions including migraine headache and cervical dystonia (spasmodic torticollis) (a neuromuscular disorder involving the head and neck).[8]
In 2009, a new form of botulinum toxin became available to Americans. Dysport (abotulinumtoxinA), manufactured by Ipsen, received FDA approval and is now used to treat cervical dystonia as well as glabellar lines in adults. In 2010, a new form of pure botulinum toxin, one free of complexing proteins, became available to Americans. Xeomin received FDA approval for medical indications in 2010 and cosmetic indications in 2011.
Botulinum toxin treats wrinkles by immobilizing the muscles which cause wrinkles. It is not appropriate for the treatment of all wrinkles - it is indicated for the treatment of glabellar lines (between the eyebrows) in adults. Any other usage is not approved by the FDA and is considered "off-label" use.
The wrinkles that occur in skin after prolonged exposure to water are sometimes referred to as pruney fingers or water aging. This is a temporary skin condition where the skin on the palms of the hand or feet becomes wrinkly. Some researchers have proposed that this wrinkling response may have imparted an evolutionary benefit by providing improved traction in wet conditions.[9]
In the recent past the common explanation was based on water absorption in the keratin-laden epithelial skin when immersed in water,[10] causing the skin to expand and resulting in a larger surface area, forcing it to wrinkle. Usually the tips of the fingers and toes are the first to wrinkle because of a thicker layer of keratin and an absence of hairs which secrete the protective oil called sebum.
In 1935, however, Lewis and Pickering were studying patients with palsy of the median nerve when they discovered that skin wrinkling did not occur in the areas of the patients' skin normally innervated by the damaged nerve. This suggested that the nervous system plays an essential role in wrinkling, so the phenomenon could not be entirely explained simply by water absorption. Recent research shows that wrinkling is related to vasoconstriction.[11][12] Water probably initiates the wrinkling process by altering the balance of electrolytes in the skin as it diffuses into the hands and soles via their many sweat ducts. This could alter the stability of the membranes of the many neurons that synapse on the many blood vessels underneath skin, causing them to fire more rapidly. Increased neuronal firing causes blood vessels to constrict, decreasing the amount of fluid underneath the skin. This decrease in fluid would cause a decrease in tension, causing the skin to become wrinkly.[13]
This insight resulted in bedside tests for nerve damage and vasoconstriction. Wrinkling is often scored with immersion of the hands for 30 minutes in water or EMLA cream with measurements steps of 5 minutes, and counting the number of visible wrinkles in time. Not all healthy persons have finger wrinkling after immersion, so it would be safe to say that sympathetic function is preserved if finger wrinkling after immersion in water is observed, but if the fingers emerge smooth it cannot be assumed that there is a lesion to the autonomic supply or to the peripheral nerves of the hand.[14]
Examples of wrinkles can be found in various animal species that grow loose, excess skin, particularly when they are young. Several breeds of dog, such as the Pug and the Shar Pei, have been bred to exaggerate this trait. In dogs bred for fighting, this is the result of selection for loose skin, which confers a protective advantage. Wrinkles are also associated with neoteny, as they are a trait associated with juvenile animals.