Category Archives: Anti-Aging Medicine

Set of skin care products

Anti-aging creams are predominantly moisturiser-based cosmeceutical skin care products marketed with the promise of making the consumer look younger by reducing, masking or preventing signs of skin aging. These signs are laxity (sagging), rhytids (wrinkles), and photoaging, which includes erythema (redness), dyspigmentation (brown discolorations), solar elastosis (yellowing), keratoses (abnormal growths), and poor texture.[1] Anti-aging supplements are a set of ingestible products that are designed to reduce or diminish the effects of aging. This includes things such as vitamin supplements, powders and teas. They are designed to reduce or diminish the effects of aging. Many products seek to hide the effects of aging while others claim to alter the body's chemical balances to slow the physical effects of aging.[2] A comprehensive grading scale for anti-aging of the skin has been validated and categorizes skin aging as: laxity (sagging), rhytids (wrinkles), and the various categories of photoaging, including erythema (redness), dyspigmentation (brown discolorations), solar elastosis (yellowing), keratoses (abnormal growths), and poor texture.[3]

Despite great demand, many anti-aging products and treatments have not been proven to give lasting or major positive effects. One study found that the best performing creams reduced wrinkles by less than 10% over 12 weeks, which is not noticeable to the human eye.[4] Another study found that cheap moisturisers were as effective as high-priced anti-wrinkle creams.[5] A 2009 study at Manchester University, funded by the manufacturer of the cream, showed that a proprietary blend of ingredients had a positive effect after six months of daily application when extrapolated to a twelve month basis of comparison.[6][7] The statistical methods used to show this have been criticized.[8]

Traditionally, anti-aging creams have been marketed towards women, but products specifically targeting men are increasingly common.[9] Marketing of anti-aging products has been criticized as reinforcing ageism, particularly against women.[10] According to Toni Calasanti of Virginia Tech, anti-aging ads specifically reinforce the belief that older people should look like middle-aged people, and that old age comes with a loss of gender identity.[11]

Anti-aging creams may include conventional moisturising ingredients. They also usually contain specific ingredients claimed to have anti-aging properties, such as:

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Anti-aging product - Wikipedia

Dermatoendocrinol. 2012 Jul 1; 4(3): 308319.

1Centre of Dermatovenereology; Vilnius University Hospital Santariskiu Klinikos; Vilnius, Lithuania

2Departments of Dermatology, Venereology, Allergology and Immunology; Dessau Medical Center; Dessau, Germany

2Departments of Dermatology, Venereology, Allergology and Immunology; Dessau Medical Center; Dessau, Germany

2Departments of Dermatology, Venereology, Allergology and Immunology; Dessau Medical Center; Dessau, Germany

2Departments of Dermatology, Venereology, Allergology and Immunology; Dessau Medical Center; Dessau, Germany

1Centre of Dermatovenereology; Vilnius University Hospital Santariskiu Klinikos; Vilnius, Lithuania

2Departments of Dermatology, Venereology, Allergology and Immunology; Dessau Medical Center; Dessau, Germany

These authors contributed equally to this work.

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

Skin aging is a complex biological process influenced by a combination of endogenous or intrinsic and exogenous or extrinsic factors. Because of the fact that skin health and beauty is considered one of the principal factors representing overall well-being and the perception of health in humans, several anti-aging strategies have been developed during the last years. It is the intention of this article to review the most important anti-aging strategies that dermatologists have nowadays in hand, including including preventive measurements, cosmetological strategies, topical and systemic therapeutic agents and invasive procedures.

Keywords: aging, anti-aging, antioxidants, laser, peeling, fillers, botulinum toxin, hormone replacement therapy, cell regulators, prevention

Skin aging is a part of a natural human aging mosaic which becomes evident and follows different trajectories in different organs, tissues and cells with time. While the aging signs of internal organs are masked from the ambient eyes, the skin provides first obvious marks of the passing time.

Skin aging is a complex biological process influenced by combination of endogenous or intrinsic (genetics, cellular metabolism, hormone and metabolic processes) and exogenous or extrinsic (chronic light exposure, pollution, ionizing radiation, chemicals, toxins) factors.1 These factors lead together to cumulative structural and physiological alterations and progressive changes in each skin layer as well as changes in skin appearance, especially, on the sun-exposed skin areas.2-12 In contrast to thin and atrophic, finely wrinkled and dry intrinsically aged skin, premature photoaged skin typically shows a thickened epidermis, mottled discoloration, deep wrinkles, laxity, dullness and roughness.13-18 Gradual loss of skin elasticity leads to the phenomenon of sagging.19 Slowing of the epidermal turnover rate and cell cycle lengthening coincides with a slower wound healing and less effective desquamation in older adults. This fact is important when esthetic procedures are scheduled.20 On the other side, many of these features are targets to product application or procedures to accelerate the cell cycle, in the belief that a faster turnover rate will yield improvement in skin appearance and will speed wound healing.21 A marked loss of fibrillin-positive structures22 as well as a reduced content of collagen type VII (Col-7), may contribute to wrinkles by weakening the bond between dermis and epidermis of extrinsically age skin.23 Sun-exposed aged skin is characterized by the solar elastosis. The sparse distribution and decrease in collagen content in photoaged skin can be due to increased collagen degradation by various matrix metalloproteinases, serine, and other proteases irrespective of the same collagen production.24-28 In older skin, collagen looks irregular and disorganized, the ratio of Col-3, to Col-1 has been shown to increase, due, significantly, to a loss of Col-1.29 The overall collagen content per unit area of the skin surface is known to decline approximately 1%/year.30 Glycosaminoglycans (GAGs) are among the primary dermal skin matrix constituents assisting in binding water. In photo-aged skin, GAGs may be associated with abnormal elastotic material and thus be unable to function effectively.31 The total hyaluronic acid (HA) level in the dermis of skin that age intrinsically remains stable; however, epidermal HA diminishes markedly.32

Three primary structural components of the dermis, collagen, elastin and GAGs have been the subjects of the majority of anti-aging research and efforts for aesthetic-anti-aging strategies pertaining to the skin, from anti-wrinkle creams to various filling agents.21

Presentation of aging of the entire face is associated with the gravity impact, muscles action, loss of volume, diminishing and redistribution of superficial and deep fat, loss of bony skeleton support what all together lead to the face sagging, changes in shape and contour. Regardless of the fact that aging is a biological inevitable process and not a pathological condition it is correlated with various skin and body pathologies, including degenerative disorders, benign and malignant neoplasms.

The successful aging paradigm, focuses on health and active participation in life, counters traditional conceptualizations of aging as a time of disease and is increasingly equated with minimizing age signs on the skin, face and body.33-35 From this perspective, preventative aesthetic dermatology might supplement the request for healthy aging, treat or prevent certain cutaneous disorders, notably skin cancer, and delay skin aging combining local and systemic methods of therapy, instrumental devices and invasive procedures.36,37 The mainspring of any skin anti-aging therapy is to achieve a healthy, smooth, blemish-free, translucent and resilient skin.38 In clinical practice, to look better doesnt mean to look younger. That is why it is so important to understand patients wishes and to orientate them to the treatment modality that will give the most satisfying results whereas knowing all available treatment techniques.39 The age, previous procedures or surgery, general health status, type of the skin, style of life and many other factors should be taken into consideration before choosing the strategy for the individual case. The desired therapeutic anti-aging effect of the skin is continuous, step-by step process, which combines various methods of the skin bio-revitalization and rejuvenation, augmentation, restoration of each skin layer individually and in the light of many other factorsfrom a style of the life to the immune, genetic, emotional and health status in general. This review will emphasize the most important topical and systemic therapeutic agents and trends in the use of invasive procedures.

The skin anti-aging strategies attempted to reverse the dermal and epidermal signs of photo- and chronological aging can be grouped under the following approaches ().

Table1. Skin antiaging approaches

Healthy and functioning skin barrier is important protector against dehydration, penetration of various microorganisms, allergens, irritants, reactive oxygen species and radiation. The skin barrier may be specifically adjusted to allow penetration. For this reason daily skin care may increase skin regeneration, elasticity, smoothness, and thus temporarily change the skin condition.40,41 However, it is necessary to stop the degradation of the skin primary structural constituents, such as collagen, elastin, to prevent the formation of wrinkles. Although the technology required to suitably deliver these compounds into the skin has not yet been developed, some products do promote the natural synthesis of these substances except elastin enhancing.42-45 Another integral approach preventing wrinkle formation is the reduction of inflammation by topical or systemic antioxidants which should be used in combination with sunscreens and retinoids to enhance their protective effects.21

Chronic photodamage of the skin manifests itself as extrinsic skin aging (photoageing). DNA photodamage and UV-generated reactive oxygen species (ROS) are the initial molecular events that lead to most of the typical histological and clinical manifestations of chronic photodamage of the skin. Wrinkling and pigmentary changes are directly associated with premature photo-aging and are considered its most important cutaneous manifestations. The strategies aimed at preventing photo-aging include sun avoidance, sun protection using sunscreens to block or reduce skin exposure to UV radiation, retinoids in order to inhibit collagenase synthesis and to promote collagen production, and anti-oxidants, particularly in combination, to reduce and neutralize free radicals (FR).21,46

Interventional studies indicate that it is in fact possible to delay skin aging and to improve skin conditions through administration of selected nutritional supplements. Nutritional antioxidants act through different mechanisms and in different compartments, but are mainly FR scavengers: (1) they directly neutralize FRs, (2) they reduce the peroxide concentrations and repair oxidized membranes, (3) they quench iron to decrease ROS production, (4) via lipid metabolism, short-chain free fatty acids and cholesteryl esters neutralize ROS.47 Endogenous antioxidant defenses are both non-enzymatic (e.g., uric acid, glutathione, bilirubin, thiols, albumin, and nutritional factors, including vitamins and phenols) and enzymatic [e.g., superoxide dismutases, glutathione peroxidases (GSHPx), and catalase]. The most important source of antioxidants is provided by nutrition. To the most known systemic antioxidants belong vitamin C, vitamin E, carotenoids, and from the trace elements copper and selenium.48-50 There are also studies demonstrating that vitamins C and E combined with ferulic acid impart both a sunscreen and an anti-oxidant effect.51

There are two main groups of agents that can be used as anti-aging cream components, the antioxidants and the cell regulators. The antioxidants, such as vitamins, polyphenols and flavonoids, reduce collagen degradation by reducing the concentration of FR in the tissues. The cell regulators, such as retinols, peptides and growth factors (GF), have direct effects on collagen metabolism and influence collagen production.

Vitamins C, B3, and E are the most important antioxidants because of their ability to penetrate the skin through their small molecular weight.52 The water-soluble, heat-labile local L-ascorbic acid (vitamin C) in concentrations between 5 and 15% was proven to have a skin anti-aging effect by inducing the production of Col-1, and Col-3, as well as enzymes important for the production of collagen, and inhibitors of matrixmetalloproteinase (MMP) 1 (collagenase 1).43,53 Clinical studies have proven that the antioxidative protection is higher with the combination of vitamins C and E than with the vitamin C or E alone.54,55 Niacinamide (vitamin B3) regulates cell metabolism and regeneration, and it is used in 5% concentration as an anti-aging agent.56 In some studies, improvement of skin elasticity, erythema and pigmentations after 3 mo of topical treatment has been observed.52,54 Vitamin E (-tocopherol) used as a component of skin products has anti-inflammatory and antiproliferative effects in concentrations between 2 and 20%. It acts by smoothing the skin and increasing the ability of the stratum corneum to maintain its humidity, to accelerate the epithelialization, and contribute to photoprotection of the skin. The effects are not as strong as with vitamins C and B3.57

An in vivo study has proven that the topical application of green tea polyphenols before UV exposure leads to an increase of the minimal erythema dose, decreases the number of Langerhans cells and reduces DNA damage in the skin.58 Other botanicals that act as antioxidants are for example the isoflavones from soya.

Cell regulators, such as vitamin A derivatives, polypetides and botanicals, act directly on the collagen metabolism and stimulate the production of collagen and elastic fibers.

Vitamin A (retinol) and its derivates (retinaldehyde and tretinoin) are also a group of agents with antioxidant effects. They can induce the biosynthesis of collagen and reduce the expression of MMP 1 (collagenase 1). Retinol is, at the moment, the substance that is most often used as an anti-aging compound and, compared with tretinoin, causes less skin irritation.59,60 It has been shown that retinol has positive effects not only on extrinsic but also on intrinsic skin aging and has a strong positive effect on collagen metabolism.60,61 Tretinoin, a nonaromatic retinoid of the first generation, is approved for application as an anti-aging treatment in a concentration of 0.05% in the United States. It has been shown to be able to reduce the signs of UV-induced early skin aging, such as wrinkles, loss of skin elasticity and pigmentation.

Polypeptides or oligopeptides are composed of amino acids and can imitate a peptide sequence of molecules such as collagen or elastin. Through topical application, polypeptides have the ability to stimulate collagen synthesis and activate dermal metabolism.62

There are various in-office procedures, most of which are intended to resurface the epidermis: to remove the damaged epidermis and replace the tissue with remodeled skin layers and sometimes spur the formation of new collagen.21,63 It is possible that the potential of GF, cytokines and telomerase will eventually be harnessed via technological advancement and innovation in the burgeoning fields of tissue engineering and gene therapy in the nearest future.64

Chemical peels are methods to cause a chemical ablation of defined skin layers to induce an even and tight skin as a result of the regeneration and repair mechanisms after the inflammation of the epidermis and dermis. Chemical peels are classified into three categories.65,66 Superficial peels [--, lipo-hydroxy acids (HA), trichloroacetic acid (TCA) 1030%] exfoliate epidermal layers without going beyond the basal layer; medium-depth peels (TCA above 30 to 50%) reach the upper reticular dermis; deep peels (TCA > 50%, phenol) penetrate the lower reticular dermis. The depth of peeling depends not on the substance used only, but on its concentration, pH of the solution and time of application.66 A number of skin modifications have been reported after several weeks: epidermal architecture returns to normal, melanocytes are present and distributed uniformly, basal cells contain small melanin grains distributed homogeneously, the thickness of the basal membrane is homogeneous, in the dermis, a new sub epidermal band of collagen appears, elastic fibers form a new network, often parallel to those of collagen.67 If superficial peelings target the corneosomes, cause desquamation, increase epidermal activity of enzymes, lead to epidermolysis and exfoliation,68,69 medium-depth peels cause coagulation of membrane proteins, destroy living cells of the epidermis and, depending on the concentration, the dermis. Deep peels coagulate proteins and produce complete epidermolysis, restructure of the basal layer and restoration of the dermal architecture.69 The depth of peel correlates with the potential side-effects, like hyperpigmentation, solar lentigines, risk of post-operative infections, especially herpetic ones.66,70 The mechanism by which the chemical peel takes effect is not clearly elucidated. An increase in collagen fiber content, water and GAG in the dermis has been reported.71,72 There is a suggestion that improvements in skin elasticity and wrinkles after chemical peeling can be attributed to increase of Col-1 with or without Col-3, elastic fibers, as well of a dense rearrangement of collagen fibers.73-76

Nonablative skin rejuvenation or subsurfacing comes as a low risk and short downtime technology which can improve aging structural changes without disruption of cutaneous integrity.77 The mechanism of action is supposed to be a selective, heat induced denaturalization of dermal collagen that leads to subsequent reactive synthesis. Nonablative skin rejuvenation is not a precise term since rejuvenation is a controlled form of skin wounding aimed at achieving a more youthful appearance after the wound heals.39

Treatment of photoaged skin has been divided into treatment of ectatic vessels and erythema, irregular pigmentation, and pilosebaceous changes (Type I) and into the improvement of the dermal and subcutaneous senescence (Type II).77 The epidermis and superficial dermis can be selectively damaged by two basic mechanisms: (a) by targeting discrete chromophores in the dermis or at the dermal-epidermal junction or (b) by utilizing mid infrared (IR) lasers.78

The devices for treatment of vascular and/or pigment irregularities include lasers emitting light at 532-, 585-, 595-, 755-, 800-, and 1064-nm wavelengths as well as filtered light generated by IPL systems equipped with different cut-off filters39,79(). Lasers emitting 1,320,80 1,450,81 and 1,540 nm82 using interstitial and intracellular water as target chromophores and pulsed dye lasers (PDL)83 using oxyhemoglobin as the primary chromophore are now employed for Type II photo rejuvenation only. The clinical efficacy of these nonablative modalities are weaker than that of the ablative methods, however, new collagen formation and clinically observable improvement in wrinkles can be observed.84,85 Reduction of facial wrinkles by using IPL devices has shown less effect comparing to laser technology,86 but for type I photo rejuvenation, IPL systems have in general shown considerably better results than laser systems operating at subpurpuric energy levels.87-90 Ultrastructural and histological analysis confirmed effectiveness of absorption of light (532, 585, 595, with or without 1064-nm Nd:YAG laser) in the blood vessels of the superficial dermis, resulting in the release of inflammatory mediators and GF into the interstitium followed by stimulated fibroblast activity and initiation of tissue repair and enhanced collagen and elastin neoformation replacing the originally damaged elastic tissue.84,91,92 An increase in grenz zone thickness,91 monoclonal chondroitin sulfate and III procollagen staining as well as quantification of Col-193 was measured after couple of treatments with PDL. The increase in dermal collagen has also been confirmed by noninvasive ultrasonographic analysis94 and radioimmunoassay.95 Nonablative skin rejuvenation should not yet be considered an alternative for laser resurfacing.39 However there are interesting data showing comparative histological changes between the ablative and nonablative modalities.96

Figure1. 45-y-old female with signs of photoaged skin: dyschromia of the skin, multiple lentigines. (A) before, (B) after one treatment with IPL with 550 nm cut-off filter.

Histological sections of skin before and after treatment with the different IPL devices have shown the formation of new collagen in the papillary and reticular dermis, as well as an increase in the number of fibroblasts and proportional decrease in the amount of solar elastosis is also usually found.92,97-99 If vascular and/or pigment disturbances improvement are immediate, the collagen remodeling response is delayed and maximum results are seen only between 3 and 12 mo after treatment.39

Laser resurfacing has been shown to be effective in counteracting photoaging through entire epidermal ablation, collagen shrinkage, stimulation of neocollagenesis, extensive dermal remodeling, regeneration of cellular organelles and intercellular attachments100 but parallelly, results in long recovery time are associated with risks of severe long lasting side effects, such as persistent erythema, hypo- or hyperpigmentation, infection or scarring.101-104

Recently, fractionated CO2-, erbium glass or erbium-YAG lasers have been introduced to reduce downtime and side effects.105 These devices emit light in a pixilated fashion onto the skin, producing an array of microthermal zones in the dermis.105-108 The controlled thermal stress to the epidermis and the dermal compartment is followed by a wound healing response ultimately leading to re-epithelization and dermal remodeling.109

Although the underlying molecular changes induced by different ablative and non-ablative as well as thermal and non-thermal skin rejuvenation treatments are not fully understood, there are investigations suggesting important roles of heat shock proteins (HSP), transforming growth factor (TGF-), different MMPs, synthethases, hyals and hyaluronic acid (HA).109-113 Type I and type III procollagen mRNA was also elevated for at least 6 mo.114

Monopolar RF is a noninvasive way to obtain skin tightening39 and immediate collagen contraction with a single treatment. Unlike lasers, the RF technology produces electric current, which generates heat through resistance in the dermis and as deep as the subcutaneous fat.78 Unfortunately there is a lack of long-term studies of efficacy and analysis of side effects for the skin using this method of skin rejuvenation.

It is obvious that different treatment modalities using visible light devices have resulted in varying clinical effects and allow to select individual treatment parameters for different indications.115 For this reason, careful simultaneous evaluation of any pigment disturbances, vascular abnormalities, wrinkles, and cutaneous sagging as skin layers are all linked is highly recommended.

The goal of skin biorejuvenation is to increase the biosynthetic capacity of fibroblasts, inducing the reconstruction of an optimal physiologic environment, the enhancement of cell activity, hydration, and the synthesis of collagen, elastin and HA (hyalorunic acid). The desired effect could be achieved by the microinjections in the superficial dermis of products containing only one active ingredient or cocktails of different compounds which are perfectly biocompatible and totally absorbable: HA, vitamins, minerals, nutrients, hormones, GF, amino acids, autologous cultured fibroblasts, homeopathic products, etc.116-121 The distinct formulations can induce strikingly divergent molecular and cellular processes in fibroblasts in vitro.122 However, more detailed studies are required to elucidate whether and how the cellular and molecular processes are involved in facial skin rejuvenation in vivo, whether these processes are similarly efficient, independent of the age of the patients. The proof of concept, including long-term efficiency, optimal injecting protocols are still lacking too.123,124

Products injected within or beneath the skin to improve its physical features by soft tissue augmentation are known as fillers.125-129 There are autologous (fat, cultured human fibroblasts), collagen (bovine-derived, human-derived from tissue culture), HA (nonanimal stabilized or viscoelastic HA from bacterial fermentation), synthetic or pseudo-synthetic implants (silicone, polymethacrylate microspheres, poly-L-lactic acid, calcium hydroxylapatite microspheres suspended in aqueous polysaccharide gel, alkyl-imide gel polymer). These may be grouped into temporary, semipermanent (lasting between 12 y), or permanent materials (lasting longer than 2 y).

GAG and particularly HA or hyaluronan are major components of the cutaneous extracellular matrix involved in tissue repair of all animal tissues.130-132 HA exhibits no species or tissue specificity. As a physical background material, it has functions in space filling, lubrication, shock absorption, and protein exclusion. In addition, HA has been implicated as a regulator of cell proliferation and locomotion.133-135 Injection of HA is thought to promote skin rejuvenation by increasing both hydration and fibroblast activation.136-140 HA injected into the skin can stimulate fibroblasts to express Col-1, MMP-1 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1)122,141 as well as is participating in wound healing, modulation of inflammatory cells, interaction with proteoglycans of the extracellular matrix, and scavenging of FR.142 All these features of HA have made it to be useful as an ideal structural compound and have raised injections of HA products to the most acceptable and scientifically investigated gold standard procedures for skin rejuvenation and augmentation ().

Figure2. Patient showing the difference of the nasolabial fold: non-treated left side (with site marks for planned HA injection) and right side straight after injection of only 0.5 ml of nonanimal stabilized cross-linked HA (Stalagmite technique on the right cheek).

Natural HA has a half-life in tissue of only 1 to 2 d before undergoing aqueous dilution and enzyme degradation in the liver to carbon dioxide and water.143 Produced from bacterial (Staphylococcus equine) fermentation and modified by chemical cross-linking to improve their resistance to enzymatic degradation and prolong their effect, non-animal reticulated HA fillers are more pure, more viscous, usually well tolerated and rarely elicit adverse and immunological reactions.130,144-146 The duration of effect for HA fillers ranges from 3 to 12 mo. The long-lasting dermal fillers maintain the position 12 y or even more.147 Modern HA fillers differ in the particulate size, cross-linking and the type of cross-linking agent used in the HA; phasic structuremono/biphasic, concentration of HA and presence of an anesthetic agent in each syringe.148-151 Besides composition, currently available products differ based on approved indications, duration of aesthetic effect, putative mode of operation, recommended depth of product placement, injection technique, suitability for different facial areas, and common adverse events.152

One of long-lasting synthetic semi-permanent dermal fillers is calcium hydroxyl apatite based filler (CaHA) suspended in an aqueous carboxymethylcelluose gel carrier.150-155 The CaHA particles act as a scaffold for new tissue formation and stimulate collagen formation around the microspheres leading to a thickening of the dermis over time.147 The spherical CaHA particles are gradually phagocytosed, degraded as calcium and phosphate and eliminated via the renal system. CaHA is biocompatible with an identical composition to bones with a low potential for antigenicity, foreign body reaction, and minimal inflammatory response. No osteoblast activity has been observed in soft tissue.155

The application of poly-L-lactic acid (PLA) in soft tissue augmentation exploits a mechanism of action not seen in any other soft tissue filler like a treatment plan, preparation of injection material, and injection technique is distinct as well.156 After the initial response lasting one week or less a delayed but progressive volumizing effect begins.157 The process of hydration, loss of cohesion and molecular weight, and solubilization and phagocytosis of PLA by the hosts macrophages, degrades PLA into lactic acid microspheres and eliminates CO2 by way of respiratory excretion. Crystals are left behind to stimulate collagen and a granulomatous reaction. This inflammatory reaction elicits resorbtion and the formation of fibrous connective tissue about the foreign body, causing dermal fibroplasia that leads to the desired cosmetic effect.158

Although subjective patient satisfaction is high in many of the studies with skin fillers and skin thickness as measured using wrinkle scale ratings of appearance, long-term efficacy and clinical safety data are lacking because patients are likely to continue to undergo subsequent cosmetic interventions.159

Autologous Platelet-rich Plasma (PRP) has attracted attention for skin rejuvenation. PRP is derived from fresh whole blood, which contains a high concentration of platelets.160 Various GF, including platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF), are secreted from the -granules of concentrated platelets activated by aggregation inducers.161 These factors are known to regulate processes including cell migration, attachment, proliferation and differentiation, and promote extracellular matrix (ECM) accumulation by binding to specific cell surface receptors.162,163 It has been shown that PRP may induce the synthesis of collagen and other matrix components by stimulating the activation of fibroblasts, thus, rejuvenating the skin.164-167 However, the molecular mechanisms underlying PRP-inducing wound healing processes are still largely unknown and experimental studies confirming the effects of PRP on aged fibroblasts are very limited.

Botulinum toxin (BTX) has no effect on skin texture and cannot discontinue the skin aging process. However, regular BTX injections can slow down the visible aging process by helping in the management of certain dynamic facial lines and wrinkles168-170(). Current treatment options of exaggerated frown lines, glabellar lines or crow feet such as surgery or implants, do not address the underlying cause of these lines, namely the excessive nerve stimulation. The mechanism of action of BTX makes it an ideal agent to target the major cause of these dynamic lines.171

Figure3. Patient showing glabellar and crows feet wrinkles. (A) pre-injection, (B) after injection with botulinum toxin.

Seven constitutionally similar but antigenically distinct subtypes of neurotoxin (A-G) are produced by different strains of the anaerobic, gram-positive bacterium Clostridium botulinum.172-177 BTX- subtype A (BTX-A) is the most potent. BTX-A produces temporary chemical denervation by blocking the presynaptic release of acetylcholine (Ach) at the neuromuscular junction (NMJ).178 The specific heavy chain is associated with the internalization of the toxin and binds it irreversibly to the motor nerve end-plates with a high affinity to specific receptors (sialoglycoproteins) in the plasma membrane of cholinergic nerve endings. This induces receptor-mediated endocytosis of the toxin. The light chain that is responsible for the toxicity splits off in the cell, and inactivates a synapse-specific protein synaptosomal-associated protein of 25 kDa (SNAP-25) which is one of several proteins required for Ach exocytosis and release into the NMJ.179

The toxin binds to presynaptic neurons of selected muscles rapidly (under an hour) and specifically. Clinically reversible chemical denervation and selective muscle relaxation or paralysis starts after 24 to 48 h and may not be completed for up to 2 weeks.173-177 In muscle, approximately on day 28, nerve sprouts mediate a partial restoration and new neuromuscular junctions are formed in the vicinity of the old junctions. Another factor explaining the regaining of muscle function could be an increase in the area of muscle membrane sensitive to acetylcholine.180 On days 6291, complete muscle function recovery can be demonstrated.179,181

Muscular changes in the form of atrophy were demonstrated in animal studies, and were completely reversible after 46 mo. In human muscle, no lasting atrophy could be detected even after repeated injections, only a predominance of type I fibers.179 The usual duration of effect is 36 mo with individual variations.173-177

Dosing of BTX-A is essential in achieving precise and predictable effects. The biological activity given in mouse units (MU) and the weight of the molecule is not associated with the dosage. One MU is equivalent to the amount of toxin at which, after intraperitoneal administration, half of the poisoned Swiss-Webster mice die (50% lethal dose; LD50).182 The amounts of BTX-A used for the treatment are 25100 times less than the LD50, so that the FDA classifies BTX-A as therapeutically safe.183 BTX-A does not cross the blood-brain barrier or pass through the skin.179

Several commercial preparations of BTX-A products which are produced from different strains of bacteria by different purification methods and therefore have distinct components and properties, requirements of storage, shelf-life, and dose are currently available for aesthetic uses.184,185

A thorough understanding and evaluation of the relevant anatomy and physiology of the muscles and possible alterations in the area to be injected is essential. Dosage for the patients depends on the area, muscle mass, gender and other factors individually. Contraindications include conditions of peripheral motor neuropathic diseases or neuromuscular functional disorders, coadministration with aminoglycoside antibiotics or other agents that interfere with neuromuscular transmission and may potentiate general weakness, treatment of patients with inflammatory skin disorders at the injection site, history of reaction to toxin, pregnancy and lactation, age younger than 12 y, participation in occupations that necessitate a wide range of facial expressions.171,186-188

Given the short-term and localized effects of BTX-A injections, it is reassuring that any potential adverse reactions known to date may also be short lived, localized, and reversible in a dose-dependent period of 68 weeks. Systemic or serious side effects in general are rare, immune-mediated disorders or other idiosyncratic reactions are unknown.189,190 The development of antibodies to BTX-A may be related to exposure to high doses of toxin and seems to be related to decreased BTX-A efficacy.191,192 Current batches of BTX-A (manufactured after 1997) have lower albumin concentration and higher toxin-specific activity, which may contribute to reduced clinical antigenicity.182,193,194

The incidence of complications in many cases depends on the proper application and the qualification of the physician. However, it has always to be considered that the benefits of this treatment are transient and repeated injections are necessary for a long-term effect.195

It is well known that there is a progressive decrease of hormone synthesis with age. Levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), melatonin (nocturnal), TSH, thyroid hormones (T3), dehydroepiandrosterone (DHEA) (sulphated form and its urinary 17-keto-metabolites), estrogens and testosterone are progressively decreasing. The main hormonal deficits in humans are menopause, andropause and partial androgen deficiency of the aging male.196-199 DHEA substitution has been proven to lead to an improvement of body condition, sexual activity, bone density, and well-being.200

In a randomized and placebo-controlled study of 280 older men and women (6079 y of age), each subject received 50 mg of DHEA daily for a year. The women showed an improvement of the libido, skin health, and osseous density.201-203Furthermore, another study conducted by Rudman et al. has pointed out that the application of GH decreased the signs of biological aging. The treatment led to an improved body condition, with an increase of muscle mass and osseous density and a decrease of adipose tissue. Moreover, an increase of skin thickness was observed.199

Melatonin has been shown to have a favorable influence on the aging process, because it has an inverse effect with regard to body weight; food restriction raises the levels of melatonin and decreases its age-related decrease. With increasing age comes a decrease of melatonin production, which may have a connection to sleep disorders suffered by elderly people. It also has be shown that melatonin can prevent tumor development and growth. Interestingly, a study showed that patients with tumors had decreased levels of melatonin compared with healthy individuals.204-207

HRT with testosterone is absolutely indicated in older men who are either symptomatic or have a low serum testosterone level. Either a decrease of testosterone or a loss of the circadian rhythm of testosterone secretion has been observed in a high percentage of older men. Clinical symptoms include general weakness, sexual dysfunction, diminished muscle and bone mass, and decreased erythropoiesis. A low testosterone level has been shown in epidemiological studies to lead to a higher morbidity and mortality rate and to a higher prevalence of depression, coronary heart disease, and osteoporosis. Insulin resistance has been shown to play an important role in the development of hypogonadism in older men. Thus, obese men and men with type 2 diabetes, show significantly lower testosterone levels compared with subjects in control groups.199

HRT with estrogen and progesterone has been long considered to have anti-aging effects; results of larger studies though, particularly of the Womens Health Initiative, have shown that an anti-aging effect is not necessarily to be expected. On the contrary, HRT has been accused to have a higher cardiovascular risk and increase of the risk of breast cancer. However, it has clear, positive preventive effects on osteoporosis, and an early, low-dose estrogen monotherapy can be considered to have advantages.208

While natural aging is genetically determined, extrinsic aging can be prevented. Aesthetic dermatology should contribute to healthy aging not only in cosmetic means by trying to erase time vestiges in skin but by also playing a significant part in prevention, regeneration, and delaying of skin aging combining knowledge of possible local and systemic therapy, instrumental devices and invasive procedures, filling the lack of scientific investigations and becoming one of the important focuses of the aging research.

No potential conflicts of interest were disclosed.

186. Botox (Package Insert). Allergan, Inc.

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Skin anti-aging strategies - PMC - PubMed Central (PMC)

From Silicon Valley investors to the new wave of longevity tech start-ups, a growing body sees ageing as something to be tracked and hacked, with your stats as much within your control as your gym PBs. But how easy is it for the average man to better his biological age? MH reviews the latest science.

Want to put the breaks on brain-ageing? A University of California, Riverside study found those who practised three skills simultaneously say, learning a language, mastering gymnastics and taking a career-boosting online tutorial had cognitive abilities decades below their actual age. In a good way, we mean. Download the Udemy app, with over 100,000 video courses, and upgrade your commute.

If you neglected to pack trainers today, dont sweat: in a University of North Florida study, participants who ran barefoot for 15 minutes improved their powers of recall by 16% in subsequent tests, while shoe-clad sprinters saw no improvement. Researchers credit the additional proprioceptive demands. Joggings backwards has been shown to have a similar effect.

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Want to wind back your biological clock without lifting a finger? Tag a sauna session on to your next workout. The University of Eastern Finland tracked more than 2,300 middle-aged men and found that those who used a sauna two or more times a week lived longer, while further studies have linked it to slower brain ageing, too.

Shrinking your calorie intake can do more than trim excess timber. Its one of the most promising methods of slowing ageing, says Varun Dwaraka, bioinformatician at anti-ageing tech company TruDiagnostic, who points to its benefits to blood sugar regulation and vascular density in the brain. That doesnt mean all-day deprivation, though. Experiment with one of these protocols.

Eat your meals during daylight hours particularly during the winter months. Its been linked to a slower rate of ageing in studies conducted on animals.

Schedule a five-day cut. A fasting-mimicking diet in which you drop your calories for a period of just a few days has been shown to switch on anti-ageing genes in research by longevity biochemist Valter Longo.

Or quit meatfor a few days a week. Some researchers believe our bodies infer a state of scarcity when on a plant-only diet, meaning flexitarianism might deliver some of the benefits of fasting.

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Cardio alone wont cut it. Maintaining strength is arguably the most important thing you can do to ensure high quality of life in middle-age and beyond, says Professor Matt Kaeberlein, an expert in ageing at UW Medicine. In fact, one study in The Journals Of Gerontology found that older men with greater muscle strength were 50% less likely to die prematurely. Focus on compound movements and lift three or four times each week, jsays Professor Kaeberlein.

Plant polyphenols such as fisetin and quercetin have the power to seek and destroy senescent cells, aka zombie cells. These are cells that essentially have been paused and start to secrete inflammatory markers, leading to frailty and disease, says TruDiagnostics Ryan Smith. Berries, apples, kiwis and grapes are top sources. As a bonus? Raising vitamin C levels has also been linked to maintaining muscle mass over the age of 50.

This year, scientists in Cambridge pioneered a new technique to reverse ageing in human skin cells by 30 years. But until thats available, try these low-cost hacks:

Drink from the (chocolate) fountain of youth. A study by Koreas Seoul National University found that 12g of cacao a day can reverse sun-related ageing, lessening the depth of fine lines. Add a spoonful to your shakes.

Top up on the sunshine vitamin. Sun damage might be the leading cause of skin ageing, but vitamin D, ironically, plays a key role in its rejuvenation. Pop a supp from October to March. And dont forget the SPF.

Plump up with collagen peptides. Research in the journal Nutrients shows this skin-boosting amino acid can reduce wrinkling and improve elasticity in 12 weeks. Vital Proteins works out at 1.40 a serving.

Inflammation ages you. In fact, Stanford scientists have even developed a test to identify your bodys inflammatory age, or iAge. One way to cool off: a separate Stanford study found that adding two or more low-sugar fermented foods or drinks to your daily diet think: kimchi, miso, tempeh and kefir has significant benefits for gut microbiome diversity, lowering vitality-sapping inflammation. Cottage cheese is another strong choice and very high in protein, too.

Research suggests an active 50-year-old can be every bit as fit as a man 30 years younger. And theres good news for the time-pressed: intensity has been found to matter more than duration. Try sprint training: a Journal Of Physiology study found that it lowered markers of inflammation (and ageing). Men in the study did three weekly sessions for six weeks, doing two or three rounds of 6-10 x 20m sprints. Run down those numbers.

Mobility matters as much as your muscle gains. Performing frequent flexibility-boosting exercises has been linked to a 24% reduced risk of functional limitation in later life, according to a Sports Medicine And Health Science review. In particular, make time to stretch out your posterior chain via toe-touches, downward dogs, lunges, etc, holding for 10 to 15 seconds. Doing so will anti-age your arteries, as well as boost your performance.

The length of our telomeres that is, the caps that protect our chromosomes is considered to be a key marker of biological ageing. And a new study from the University of Leicester has found a surprisingly simple way to hack them: quit dawdling. By studying the genetic data of more than 400,000 Brits, theyve estimated that a lifetime of brisk walking could take 16 years off a persons biological age by midlife.

Hormone therapy is on the rise among middle-aged men chasing eternal youth. But before you dabble in doping, try some of these far simpler testosterone-raising strategies:

Fill up on fats. Research has consistently linked the monounsaturated fats found in the likes of olive oil, avocado and nuts to higher testosterone. Meats not the only man food.

Go for a daily walk before work. Not only does early-morning sun exposure benefit your sleep (a lack of which tanks T levels), it also raises sex hormone levels, according to Tel Aviv scientists.

Watch your waistband. A four-point increase in your BMI can accelerate age-related testosterone decline by 10 years, particularly when fat accumulates around your middle.

The gold star in your spice rack, turmeric has been linked to everything from pain relief to immunity. A study from Syracuse University adds further bulk to this list of benefits, with animal studies showing that it can counteract age-related muscle loss, while the University of Tehran reports it might be able to reduce cellular damage, too. Knock back a juice shot at breakfast.

More than a quarter of us only visit the dentist when we have a major problem. But its worth booking in for a check-up. According to Andrew Steele, scientist and author of Ageless, better dental hygiene is one of the best ways to stave off the risk of heart disease and dementia, by eliminating the low-level gum inflammation that can accelerate age-related illness.

The number of people over 30 with high blood pressure has doubled over the past three decades and its accelerating the rate at which our brains are ageing, reports Frontiers In Aging Neuroscience. Aside from the obvious factors exercise, sleep, stress and alcohol the newest research suggests scoring your protein from a wider variety of sources can have a huge impact, dragging down your risk by two thirds. Mix up your meat with seafood, beans and eggs.

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22 Ways To Look and Feel 5 Years Younger - Men's Health

A DERMATOLOGIST'S mom has told her about an unusual beauty routine that she says slows down aging.

Skincare influencer Dr Mamina Turegano (@drmamina) uploaded a video of the 72-year-old Japanese woman demonstrating an ancient skincare process.

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Dr Turegano shared the skincare secret as part of a series on the "sometimes-strange anti-aging tips I learned from my Japanese mom."

The video kicks off with a photo of Turegano with her mom, whose skin is clear and minimally lined.

The older woman is then shown demonstrating how to use a small wooden brush to sweep all over the skin.

The doctor goes on to explain how the anti-aging technique is called "dry brushing" and is used in Ayurvedic medicine.

She is quick to add that although there's no scientific evidence to back up the routine, it may improve the skin.

"It's thought to have benefits like exfoliation and increasing circulation," she claims.

The video then switches to Dr Turegano's mom talking as she quickly performs the brushing routine.

She stands confidently, holding her small wooden brush, and begins sweeping the bristles all over her body.

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"I usually do two to three minutes every morning," she says quietly.

"You'll have all clothes off of course. Totally naked alright?" she adds with a smile.

The video continues to show her mom lying flat on her back, brushing her bare legs.

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She describes the importance of traveling up towards the heart.

Commenters are impressed, with one saying: "She is GLOWING"

Another added: "She has aged gracefully."

But one follower is skeptical and said: "My skin would turn red and bleed."

At the end of the video, Mamina's mom happily holds up her brush while still wearing her gym shorts and T-shirt.

She grins and says: "Happy brushing!"

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My mom taught me an anti-aging tip it looks strange but it works, people cant believe shes 72... - The US Sun

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Before you apply yet another anti-aging cream, serum, or other product, stop right there you could be using it all wrong. Many people are unknowingly applying some of the most effective ingredients to their skin all wrong. As a result, they are wasting both precious time and money on products that could be effective if used correctly. From sunscreen tips to retinol mistakes, these are the anti-aging products skincare experts say youre using all wrong.

For starters, you are probably not applying sunscreen daily, which means youre missing out on opportunities to protect your skin from the damaging, aging effects of UV light, whether its July or December.

Preventative care is the most important step inanti-aging, says Dr. Adrienne OConnell, medical director and president ofLaguna Beach Aesthetics. You must wear sunscreen that protects against both UVA and UVB rays (broad spectrum) with an SPF 30 or higher every single day, no matter the weather. I highly recommend a 100% mineral sunscreen, which is much safer for sensitive skin and contains no added chemicals.

The second most misused product is Retinol, according to Dr. OConnell.As the ultimate go-to skincare ingredient for a younger look, retinol speeds up your cell turnover so your body can replace damaged surface cells with brighter, younger skin cells, Dr. OConnell says.More is not better when it comes to this product. It can over-dry or irritate your skin.It is also dangerous to use in the morning because it makes your skin more sensitive to sunlight.

If you choose to use a Retinol product, Dr. OConnell says it is best used at night and washed off in the morning.You also must apply sunscreen in the morning as an added precaution, Dr. OConnell says.Also, start slow.Use the product once a week and gradually increase until you are using it according to the products instructions and never use more than the instructions direct you to.

Often, people buy the products they see on TV or are advertised by a favorite celebrity without caution, warns Dr. Nadir Qazi, DO, a board-certified physician, cosmetic dermatology surgeon, and owner ofQazi Clinic. Then when you look at the ingredient list it can contain ingredients known to cause harm to skin instead. For example, a product may contain retinol to combat wrinkles, Dr. Qazi says. However, if that same product contains a coconut oil derivative like Coco-Caprylate, the product might slow wrinkling but clog the pores and cause acne.Or they may only put a small amount of active ingredients in the product. Suppose an under-eye cream advertises vitamin C as its main active ingredient. Then, using a name like sodium ascorbate, they put it at the bottom of the ingredients list. All the while, that product uses silica as a main ingredient and filler to smooth the appearance of under-eye circles while using the product without treating them.

Thats why Dr. Qazi says its imperative to look at ingredients and do your own research on whether a product can be harmful or beneficial.

Exfoliation is wonderful it makes the skin fresh and rejuvenated, Dr. Qazi says. It feels so nice and vibrant that people are often tempted to exfoliate more often than they should, and with products that do more harm than good.

Over-exfoliation makes the skin sensitive and inflamed, and the skin can begin to flake and peel away, Dr. Qazi says. In addition, as skin becomes dehydrated from over-exfoliating, collagen breaks down, which causes the skin to lose its firmness and elasticity, creating wrinkles.

To maintain a youthful glow, chemical exfoliants are a good substitute for the abrasive scrubs one might have used growing up, Dr. Qazi says. Look for alpha-hydroxy acids like glycolic and mandelic acids. These acids exfoliate efficiently, and it is easy to find lower concentrations or limit how often you use them to avoid over-exfoliation. Mandelic acid can be especially beneficial for sensitive skin as it has a larger molecular structure and is very gentle as an exfoliant.

It isnt enough to own a bathroom medicine cabinets worth of expensive anti-aging skincare products. Learning which ones you could be using wrong is key to getting healthier, more glowy skin at any age.

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4 Anti-Aging Products Youre Using All Wrong, According To Skincare Experts - SheFinds