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Molecular Mechanisms of Skin Aging: State of the Art
Abstract
The process of skin aging in humans is complex and is induced by multiple factors, including genetic and various environmental ones. In particular, the superposition of environmental factors, such as UV irradiation on skin, results in massive wound-like morphological alterations mainly of the dermis. In sun-protected areas the most pronounced changes occur within the epidermis and affect mostly the basal cell layer. As a result, while sun-protected aged skin appears thin, finely wrinkled, and dry, photoaged skin is characterized by deep wrinkles, laxity, and roughness. Although the fundamental mechanisms are still poorly understood, a growing body of evidence points toward the involvement of multiple pathways in the generation of aged skin. Recent data obtained by expression-profiling studies and studies of progeroid syndromes (e.g., Hutchinson-Gilford progeria, Werner syndrome, Rothmund-Thomson syndrome, Cockayne syndrome, ataxia teleangiectasia, and Down syndrome) illustrate that among the most important biological processes involved in skin aging are alterations in DNA repair and stability, mitochondrial function, cell cycle and apoptosis, ubiquitin-induced proteolysis, and cellular metabolism. One of the major factors that has been proposed to play an exquisite role in the initiation of aging is the physiological hormone decline occurring with age. However, hormones at age-specific levels may not only regulate age-associated mechanisms but also regulate tumor-suppressor pathways that influence carcinogenesis. Understanding the molecular mechanisms of aging may open new strategies in dealing with the various diseases accompanying aging, including cancer.
... Genetics play a significant role in determining how we age, influencing everything from skin elasticity to the appearance of wrinkles. Research has shown that genetic variations can account for differences in how individuals experience the aging process [5][6][7]. Additionally, epigenetic factors-heritable changes in gene expression that do not involve changes to the DNA sequence-can also influence aging. Environmental factors such as UV exposure, diet, and stress can cause epigenetic modifications that accelerate the aging process [8]. ...
... Several studies delved into the molecular mechanisms underlying skin aging. For instance, Shin et al. (2019) [5] and Makrantonaki and Zouboulis (2007) [7] provided indepth reviews of the biochemical pathways that contribute to dermal aging, while Fisher et al. (2008) [12] discussed the collapse of fibroblasts in aging skin and its therapeutic implications. Horvath (2013) [8] introduced the concept of DNA methylation age, presenting a biomarker for aging consistent across human tissues, which is crucial for understanding biological age at a cellular level. ...
... Several studies delved into the molecular mechanisms underlying skin aging. For instance, Shin et al. (2019) [5] and Makrantonaki and Zouboulis (2007) [7] provided indepth reviews of the biochemical pathways that contribute to dermal aging, while Fisher et al. (2008) [12] discussed the collapse of fibroblasts in aging skin and its therapeutic implications. Horvath (2013) [8] introduced the concept of DNA methylation age, presenting a biomarker for aging consistent across human tissues, which is crucial for understanding biological age at a cellular level. ...
Background
The aging paradox highlights the coexistence of increased life expectancy with a persistent desire to maintain a youthful appearance, driven by biological, psychological, and social factors. Advances in healthcare have extended human lifespans, yet societal pressure to appear youthful remains strong. Understanding the genetic, epigenetic, and environmental contributors to skin aging is crucial for optimising aesthetic procedures.
Methods
This literature review synthesises research on the aging paradox, genetic influences on skin aging, and the effectiveness of non-surgical aesthetic interventions. The review involved a comprehensive search across databases including PubMed, Google Scholar, Web of Science, and Scopus using keywords like “aging paradox”, “genetic imprint”, “non-surgical aesthetics”, “epigenetics”, and “anti-aging treatments”. Studies were selected based on relevance, credibility, recency, and diversity of perspectives.
Results
The review identified 64 studies relevant to the aging paradox and non-surgical interventions. These studies underscore the significant roles of genetic variations and epigenetic mechanisms, such as DNA methylation and microRNA regulation, in determining aging trajectories and treatment responses. The proposed “PERSONAL” (Personalised Epigenetic Regime for Skin Optimisation, Nurturing Aesthetic Longevity) paradigm advocates for a comprehensive, personalised approach, integrating genetic and epigenetic profiling to tailor treatments to individual needs.
Conclusions
By leveraging the complex interplay of genetic, epigenetic, and environmental factors, practitioners can enhance the precision and efficacy of non-surgical aesthetic interventions, improving patient satisfaction and promoting long-term skin health. Continuous monitoring and iterative adjustments within this paradigm are essential for achieving optimal outcomes.
Level of evidence: Level 4, therapeutic study
... Intrinsic factors include genetic predispositions and metabolic processes, while extrinsic factors encompass environmental influences such as smoking, poor diet, air pollution, and particularly ultraviolet (UV) radiation, which leads to photo-aging (2)(3)(4). UV exposure affects up to 80% of facial skin, altering the differentiation of epidermal keratinocytes and reducing the expression of critical proteins like β1-integrin and type VII collagen, thereby contributing to wrinkle formation (5)(6)(7)(8). These changes underscore the complex interplay between genetic and environmental factors in skin aging, necessitating extensive research to develop effective anti-aging treatments (8)(9)(10). ...
... UV exposure affects up to 80% of facial skin, altering the differentiation of epidermal keratinocytes and reducing the expression of critical proteins like β1-integrin and type VII collagen, thereby contributing to wrinkle formation (5)(6)(7)(8). These changes underscore the complex interplay between genetic and environmental factors in skin aging, necessitating extensive research to develop effective anti-aging treatments (8)(9)(10). ...
Background: The cosmetics industry has seen significant growth due to the pursuit of beauty and the increasing demand for anti-aging agents. These agents, derived from active ingredients like polyphenols, retinol, and pro-xylane, are categorized into synthetic, plant, and fermentation components. Among these, synthetic components such as vitamins A, B, and C are widely used. Vitamin C has long been utilized in food and medicine for its beneficial effects, including its crucial role in collagen formation. The aging process, while slow and prolonged, is significantly influenced by vitamin C, making it an indispensable component for skin health. Objective: This study aimed to determine how vitamin C helps reduce aging and controls the mechanisms associated with skin aging. Methods: A comprehensive narrative review was conducted by synthesizing existing literature from electronic databases such as PubMed, Scopus, and Google Scholar. The search included keywords like "Vitamin C," "skin aging," "collagen synthesis," "oxidative stress," and "melanogenesis." Studies included were peer-reviewed, written in English, and published within the last 20 years. Both in vivo and in vitro studies were considered to assess the biochemical functions of vitamin C, its protective roles against UV radiation, and its therapeutic potential in various skin conditions. Data were critically analyzed, focusing on study designs, sample sizes, and statistical analyses. Results: Vitamin C was found to enhance collagen synthesis, with studies showing a significant increase in collagen production (Makrantonaki & Zouboulis, 2007). Its antioxidant properties effectively neutralized reactive oxygen species, reducing oxidative stress and preventing DNA damage, with a reduction of ROS levels by 30-50% in UV-exposed skin cells (Rinnerthaler et al., 2015). Inhibitory effects on melanogenesis were observed, with vitamin C reducing melanin synthesis by 25% (Shimada et al., 2009). Additionally, therapeutic benefits were noted in treating acne, psoriasis, and hyperpigmentation, with a 40% improvement in acne scars (Chawla, 2014) and a 35% reduction in psoriasis symptoms (Soodgupta et al., 2014). Conclusion: Vitamin C plays a crucial role in maintaining skin health and combating aging through various mechanisms, including enhancing collagen synthesis, providing antioxidant protection, inhibiting melanogenesis, and treating skin diseases. Its consistent findings across multiple studies support its continued use in clinical and cosmetic dermatology. Further research with standardized methodologies is recommended to optimize its application and fully understand its potential.
... Although a greater number of cells possess the potential of about 60-70 postnatal doublings, over the period, they do not proliferate but remain viable and become more susceptible to apoptosis [62,67]. This process is called the biological clock [8,12,62,63,68]. Along with this process, some signaling molecules increase while some decrease in number [62,63]. ...
... Along with this process, some signaling molecules increase while some decrease in number [62,63]. A decrease or increase in the number of signaling molecules like chemokines and cytokines leads to the damaging of several skin functions and results in fibroblast senescence [62,68]. All these factors decrease O n l i n e F i r s t lipophilicity readily passes through the phospholipid bilayer membrane of the cell and has good absorbability [45]. ...
Millions of people around the world fall within the age group of 35 and above; having fluctuating lifestyles, increased exposure to blue light, and a faster-depleting ozone layer that enhances entry of UVA and UVB rays in the skin which tends to age faster leading into collagen degradation that results in fine lines and decreased cell senescence. The goal of skin rejuvenation is to have healthy skin. Cosmeceuticals incorporating retinoids have been increasingly used over the past few years to promote collagen synthesis and rejuvenate the skin. Photo-induced and chronological aging processes are decelerated with retinoid application that endorses skin elasticity by free radical neutralization, new cell growth, and blood vessel promotion within the skin to help fight pigmentation and reduce fine lines. Retinoids are commercially available as creams and serums for topical application. Nanotechnology is used in the development of retinoids to counteract adverse reactions like skin irritation and purging to improve its stability, efficacy, and acceptability. Emerging studies on retinoids include formulating them within liposomes, solid lipid nanoparticles, nano-emulgels, and hydrogels. This review details understanding the aging process, the mechanism of action of retinoids to counterfeit aging, and the potential use of nanotechnological delivery in cosmeceuticals.
... In contrast to the brain, in normal circumstances in the healthy epidermis, cell growth and renewal persist into maturity, though less rapidly with older age: intrinsic and photo-aging of the human skin subsequently reflect impairment of several mechanisms, including reduced epidermal proliferation, impaired melanocyte function, and decreased collagen biosynthesis [21][22][23]. The aged epidermal layer is thinner due to a decrease in keratinocyte proliferation and differentiation. ...
... Immunohistochemistry was performed on young photoprotected (ages [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], middle photo protected (ages 37-45), aged photo protected (ages 50-70), and aged photo-exposed (ages 48-83) skin samples. All samples were paraffin embedded and sectioned to generate 5µm thick samples. ...
T14 is a 14mer peptide derived from the C-terminus of acetylcholinesterase (AChE). Once cleaved, it is independently bioactive of the parent molecule and enhances calcium influx in different cell types, in a range of scenarios: it binds to an allosteric site selectively on the alpha-7 receptor, where it modulates calcium influx and is thus a potential trophic agent, as already reported in a range of normal developmental scenarios. However, if inappropriately activated, this erstwhile beneficial effect converts to a toxic one, resulting in pathologies as disparate as Alzheimer's and various metastatic cancers. Given that epidermal keratinocyte cells have the same ectodermal origin as brain cells, as well as expressing AChE and the alpha-7 receptor, we have explored whether T14 plays a comparable role. Here we report that the T14 immunoreactivity is detectable in human keratinocytes with levels inversely related to age: this decrease is even more apparent with chronic photo-exposure and thus accelerated skin aging. We conclude that T14, an agent promoting cell growth and renewal in other parts of the body, also operates in skin, Moreover, monitoring of keratinocyte T14 levels might offer further insights into the now well reported link between degenerative diseases and epidermal cell profile.
... The ECM is composed of fibrous collagen and associated proteins, and cell-ECM interactions in the skin play a crucial role in maintaining homeostasis and influencing aging. These interactions are affected by various external factors, such as ultraviolet (UV) exposure, which contributes to skin photoaging by impacting collagen degradation and altering elastic fiber levels [14,15]. Symbiotic organisms also influence the skin. ...
Intestinal mucosal tissues are prone to infections, often leading to inflammation. Lactic acid bacteria in the gut can modulate these inflammatory responses, but the interaction between host cells and lactic acid bacteria remains unclear. This study examines how Lactiplantibacillus plantarum HY7714 alleviates intestinal inflammation using gut-on-a-chip technology and in vitro models. Inflammation was induced using a gut-on-a-chip, and changes in cell morphology and barrier function were analyzed. Extracellular vesicles (EVs) derived from HY7714-improved intestinal cell structure repaired damage and restored tight junction integrity. Additionally, they attenuated inflammatory cytokines by regulating the MyD88/mTOR/NF-κB signaling pathway. RNA sequencing revealed downregulation of vicinal oxygen chelate (VOC) family proteins and proline aminopeptidase, both linked to inflammation and extracellular matrix interactions in skin health. Therefore, we explored the effects of HY7714 EVs on skin cells. The findings showed that HY7714 EVs reduced cytotoxicity and downregulated metalloproteinase expression in skin cells exposed to UVB radiation, indicating their potential anti-aging and anti-photoaging properties. These findings suggest that HY7714-derived EVs enhance both intestinal and skin health by reducing inflammation and improving barrier function, with potential benefits for the gut–skin axis.
... photoaging share common biochemical mechanisms that result in altered skin structure and function, such as decreased collagen production and increased collagen degradation. 6 Environmental elements such as UV radiation wield considerable influence in triggering morphological changes in the skin, resulting in profound wrinkles, laxity, and roughness. With advancements in molecular biology, newer insights into combating skin senescence have emerged, emphasizing the importance of tailored anti-aging therapies that address epidermal dysfunction, dermal matrix aberrations, and other agerelated skin problems. ...
Skin aging is a complex process affected by both internal and external factors, leading to changes in skin structure and function. The connection between signs of skin aging and age is intricate, involving genetic, environmental, and lifestyle influences. However, relying solely on chronological age fails to accurately predict skin aging due to the complex interplay of these factors. Interventions such as retinoids show promise in altering skin aging processes, questioning the exclusive use of chronological age for predictions. Skin aging goes beyond appearance, reflecting deeper changes in skin function and structure. Therefore, comprehensive strategies including sun protection and topical treatments are essential for managing aging effects. In essence, understanding the intricate nature of skin aging and adopting holistic approaches tailored to individual factors are vital for promoting skin health throughout life.
... Extrinsic ageing is a distinct process caused by external factors such as UV exposure and the individual lifestyle (tobacco, pollution, nutrition). [3][4][5] Unlike cosmetic surgery, which consists of invasive procedures performed by a surgeon, aesthetic medicine includes superficial, non-invasive procedures that are performed on an ambulatory mode and for which the results are obtained rapidly or even immediately, without social eviction. These non-invasive techniques are therefore increasingly attractive. ...
Background: Aging is triggered by both intrinsic and external factors. Although chemical peels with trichloroacetic acid (TCA) are used to reduce wrinkles and hyperpigmentation, they cannot help to enhance the other factors that contribute to overall skin quality. Objective: The aim of this case series was to compare the efficacy of 15% TCA peel alone versus a combination of NCTF®135HA injection and 15% TCA for face rejuvenation. Methods: Six patients were treated on each side of their face with 15% TCA combined or not with NCTF®135HA. Each patient was subjected to one session of peeling on both sides of the face followed by three sessions of NCTF®135HA injections, on only one randomized side of the face, with an interval of two weeks between each treatment. Skin aging measures were assessed before and after treatments (D0 and D45). Results: At D45, clinical scoring demonstrated a significant difference in reducing the lower face sagging score, increasing skin hydration, and improving skin homogeneity on the side treated with NCTF®135HA combined with peeling compared to the side treated with peeling alone. There is a tendency for improvement in Crow’s feet only on the side treated with both peeling and NCTF®135HA, compared to the side treated with peeling alone. Both the evaluator and the patient reported a greater improvement on the side of the face treated with 15% TCA + NCTF®135HA on the Global Aesthetic Improvement Scale (GAIS). Conclusions: The addition of NCTF®135HA to 15% TCA chemical peel application significantly enhanced the peeling effect on skin aging features, this improvement was perceived by both subjects and the physician.
... Intrinsic aging represents an inexorable physiological process driven by genetic factors. Conversely, extrinsic aging is induced by external environmental stressors such as temperature fluctuations, pollution, and UV radiation (Makrantonaki and Zouboulis 2007). UV radiation-induced skin aging, referred to as photoaging, manifests as deepening wrinkles, hyperpigmentation, an uneven skin texture, and skin redness (Kovacs et al. 2009). ...
Ultraviolet (UV) radiation causes skin damage including oxidative stress, inflammation, and photoaging. Extremophile fermentation products have been found to effectively protect the skin from UV-induced damage. This study aimed to investigate the impact of acid-induced stress on the content of bioactive compounds, as well as the anti-inflammatory and anti-photoaging properties of sorghum fermentation by the extremophilic Monascus pilosus. The study compared acid-stress fermentation (ASF) of sorghum with conventional fermentation (CF) and examined differences in total phenolic content, antioxidant activity, and short-chain fatty acid levels. Using gas chromatography–mass spectrometry assay, the ASF sample had lower total phenolic content compared to CF, but significantly higher levels of short-chain fatty acids. Butyric acid was the predominant metabolite in the ASF sample, followed by propionic acid. The ASF sample exhibited superior protection for UV-irradiated human keratinocytes by inhibiting apoptosis, reducing ROS, and downregulating inflammatory mediators. It also decreased metalloproteinases expression levels, increased collagen and elastin production, and mitigated UV-induced photoaging. The effects of ASF samples were evaluated in volunteers, and the results confirmed the ASF sample’s effectiveness in ameliorating UV-induced skin symptoms, including pigmentation, redness, and wrinkles. These findings conclude that acid-stress enhances the anti-inflammatory and anti-photoaging capabilities of Monascus pilosus fermented sorghum.
... Skin can be aged by both natural and artificial radiation sources [28]. Either way, photoaging alters the composition of the extracellular matrix, suppresses the immune response and induces immunotolerance [29]. These changes can lead to the development of skin cancers and precancerous conditions [27,[30][31][32][33][34][35]. ...
The incidence of skin cancer continues to grow. There are an estimated 1.5 million new cases each year, of which nearly 350,000 are melanoma, which is often fatal. Treatment is challenging and often ineffective, with conventional chemotherapy playing a limited role in this context. These disadvantages can be overcome by the use of nanoparticles and may allow for the early detection and monitoring of neoplastic changes and determining the effectiveness of treatment. This article briefly reviews the present understanding of the characteristics of skin cancers, their epidemiology, and risk factors. It also outlines the possibilities of using nanotechnology, especially nanoparticles, for the transport of medicinal substances. Research over the previous decade on carriers of active substances indicates that drugs can be delivered more accurately to the tumor site, resulting in higher therapeutic efficacy. The article describes the application of liposomes, carbon nanotubes, metal nanoparticles, and polymer nanoparticles in existing therapies. It discusses the challenges encountered in nanoparticle therapy and the possibilities of improving their performance. Undoubtedly, the use of nanoparticles is a promising method that can help in the fight against skin cancer.
... (3,4) The aging process of skin cells is a complex process induced by a multitude of internal and external factors, such as gene mutations, hormones, ultraviolet irradiation, and pollution. (5) Skin degradation compromises the integrity of skin's structure, leading to the loss of body function. (6) Previous studies reported that excessive stimulation of reactive oxygen species (ROS), i.e. more than the cellular antioxidant protection system can balance, results in oxidative damage to cells. ...
... The pathological findings of photoaged skin include not only solar elastosis and basophilic degeneration but also the atrophy of the dermis and subcutaneous layer of the skin, suggesting that although these skin layers are difficult to penetrate for ultraviolet (UV) rays, prolonged sun exposure induces abnormalities in these layers. This phenomenon commonly occurs in areas of thin skin that are constantly exposed, such as that of the face 1,2 . ...
Background
Poly-L-lactic acid (PLLA), a synthetic, biocompatible, and biodegradable polymer, has been safely used in several clinical applications. Recently, PLLA has been widely used in the field of dermatology to treat wrinkles in aging skin. Reportedly, PLLA directly acts on dermal fibroblasts causing a significant increase in the expression of type I collagen. However, little is known about the effect of PLLA on adipocytes.
Objective
This study aimed to analyze the effect of PLLA on adipocytes and examine its potential in treating deep wrinkles engendered by the loss of subcutaneous fat because of aging and photoaging.
Methods
To elucidate the effect of PLLA on skin photoaging, cultured 3T3-L1 adipocytes were irradiated with ultraviolet B (UVB) rays. Oil red O staining was used to detect lipid accumulation in the adipocytes. Real-time quantitative polymerase chain reaction and Western blotting were performed to detect types IV and VI collagen mRNA and protein levels, respectively, under different conditions.
Results
The differentiation of 3T3-L1 cells enhanced adipogenesis and the expression of types IV and VI collagens, both of which were inhibited by UVB irradiation. Following this irradiation, PLLA stimulated adipogenesis and the expression of types IV and VI collagens.
Conclusion
PLLA may provide the beneficial effect on adipocytes from the aspect of adipogenesis and collagen expression in the subcutaneous adipose tissues.
... Exogenous factors pertain to extrinsic ageing [42], characterized by more significant changes. The cumulative impact of these alterations operates synergistically, influencing cellular structures within the skin tissue which are discernible through the biochemical differences by changes in molecular vibrations shown in Raman spectra, showing the need for invasive procedures, a feature underscored by other researchers [4,9,17,29,[43][44][45]. ...
... As the largest organ of the body, the skin is the barrier between the cells and the external environment, covering most of the body (3). Regarding the mechanism of skin aging, it has been shown to be related to damage to collagen and elastic fibers by matrix metalloproteinases, extracellular matrix degradation, abnormal fibroblast function, oxidative stress and cell proliferation, apoptosis and inflammatory response, and light-induced DNA damage (4)(5)(6). Pigmentation, dryness, loss of elasticity and deepening of wrinkles are all significant changes in skin aging. Topical cosmetics are the most basic form of skin care (7,8). ...
Background
In recent years, oral various fruits or supplements of fruits natural extracts have been reported to have significant anti-aging effects on the skin (1, 2), However, despite many studies on this topic, there is often no clear evidence to support their efficacy and safety. In this paper, we present a comprehensive review and Meta-analysis of the evidence for the safety and efficacy of oral fruits and fruits extracts in improving skin aging.
Methods
Four databases, Pubmed, Embase, Web of Science, and Cochrane Library (CENTRAL), were searched for relevant literature from 2000–01 to 2023–03. Seven randomized controlled trials (RCTs) of fruit intake or fruit extracts associated with anti-skin aging were screened for Meta-analysis.
Results
Compared to placebo, oral intake of fruit or fruit extracts showed significant statistical differences in skin hydration and transepidermal water loss (TEWL), with a significant improvement in skin hydration and a significant decrease in TEWL. No significant statistical difference was observed in minimal erythema dose (MED), overall skin elasticity (R2), or wrinkle depth, and no evidence of significant improvement in skin condition was observed.
Conclusion
Meta-analysis results suggest that consume administration of fruits or fruit extracts significantly enhances skin hydration and reduces transcutaneous water loss, but there is insufficient evidence to support other outcome recommendations, including minimal erythema dose (MED), overall skin elasticity(R2), and wrinkle depth.
Systematic Review Registration
PROSPERO (york.ac.uk), identifier CRD42023410382.
... Intrinsic aging is highly related to chronological age and genetic factors aggravated by free radicals and hormonal influences. Extrinsic aging is a distinct process caused by external factors such as UV exposure and the individual lifestyle (tobacco, pollution, nutrition) [6] [7] [8]. ...
... There is a relationship between temulawak extract and anti-aging on the skin by inducing a cellular response in normal human skin fibroblasts, which causes the induction of peroxides and other antioxidant enzymes to modulate aging and improve cell function 12 . Oxidative stress and inflammation mostly contribute to aging and agerelated conditions including skin aging 13,14 . ...
Temulawak is known for its potential as a powerful antioxidant, anti-inflammatory, and anti-aging. Numerous studies have been reported on how temulawak extract components minimize wrinkles, boost collagen production, and prevent degradation. This study aims to determine whether temulawak extract promotes wound healing in Wistar rats. Pure experimental laboratory research and only post-test control group design observations have been done. Our results showed changes in the macroscopic appearance of wounds, particularly in the look of closed, dry wounds, which were exclusively observed in patients who received ointments containing 15%, 20% and 25% temulawak extract after 14 days. Based on the histopathology observation there was a significant difference in the mean comparison of the area of epithelialization, the number of fibroblasts, and the quantity of angiogenesis. We conclude that temulawak extract benefited incision wound healing in Wistar rats.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Современная косметология предлагает широкий выбор процедур и препаратов для улучшения качества кожи, среди которых особое место занимают скинбустеры. Приведены подробные характеристики препаратов-скинбустеров итальянской компании MP System, описано их воздействие на кожу, даны рекомендации к их применению в превентивной терапии.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Аквапорины представляют собой группу белков, которые обеспечивают трансмембранный транс- порт воды [1]. К настоящему времени у челове- ка описаны 13 видов аквапоринов (AQP0–AQP12), которые экспрессируются в различных органах и тканях. Белки семейства аквапоринов «прошнуро- вывают» клеточную мембрану, образуя поры/кана- лы, обеспечивающие трансмембранный перенос в клетки небольших полярных растворенных веществ. Так, AQP7 и AQP9 транспортируют глицерин; AQP7, AQP9 и AQP10 переносят мочевину, а AQP1 – угле- кислый газ. AQP3 – самый распространенный аквапорин кожи, обеспечивающий транспорт не только воды, но и глицерина, играя, таким образом, важнейшую
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Сегодня актуальным трендом в эстетической медицине стал принцип максимального сохранения социальной активности пациентов. Сократить кратность сессий и количество инъекций в рамках одной процедуры, уменьшить риск возникновения нежелательных сопутствующих явлений и пролонгировать клинический эффект можно путем повышения устойчивости гиалуроновой кислоты к ферментному лизису эндогенной гиалуронидазой и увеличения диффузии препарата в коже. Описаны отечественные препараты, соответствующие данным требованиям; приведены протоколы их применения.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Основой длительной эритемы служат телеангиоэктазии. Описан сложный случай лечения телеангиоэктазий у пациентки с отягощенным анамнезом, в ходе которого кроме лазерных и световых процедур применяли имплантируемые гидрогели линии СФЕРО®гель. Показано, что данные препараты улучшают трофику кожи, повышают ее антиоксидантный и детокс-потенциал.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Применение липофилинга в качестве одного из методов реконструкции у больных с посттравматической деформацией челюстно-лицевой области приобретает все большую популярность благодаря простоте методики, низкой частоте послеоперационных осложнений, удовлетворительным эстетическим результатам и регенеративному воздействию аутожира на ткани. Приведены случаи из клинической практики.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Учет анатомических и функциональных особенностей мимических мышц – непременное условие эффективной и безопасной ботулинотерапии. Классическая схема блокировки m. procerus работает далеко не всегда. Чтобы добиться хорошего эстетического эффекта, необходимо учитывать анатомические особенности строения мышц в зоне глабеллы каждого пациента. Представлена авторская методика выполнения ботулинотерапии данной зоны, в соответствии с которой в мышцы-депрессоры периорбитальной области следует инъецировать большие дозы препарата и распределять их, используя большое количество точек ввода.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Высокоинтенсивный фокусированный ультразвук (HIFU) оказывает омолаживающее действие на кожу с признаками фотостарения. В клинической практике процедуру применяют как один из методов стимуляции синтеза коллагена, уменьшения дряблости кожи, улучшения ее текстуры и устранения мелких морщин. Подробно описано исследование на животных, показавшее фотостарение кожи. Показана целесообразность применения высокоинтенсивного фокусированного ультразвука для коррекции морфологических признаков старения кожи.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Нарушение микроциркуляции – важнейшее звено патогенеза возрастных эстетических дефектов кожи. С возрастом происходит облитерация просвета капилляров, исчезающие капилляры замещаются соединительной тканью, уменьшается транскапиллярный кровоток, нарушается доставка кислорода и энергетических субстратов к коже, а также эвакуация отработанных продуктов ее жизнедеятельности. Это приводит к формированию морщин, гравитационных изменений, ухудшению барьерной функции. В доказательство этого предположения авторы провели соответствующее клиническое исследование.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Профилактическая мастэктомия – операция, позволяющая сохранить жизнь и здоровье женщинам из группы повышенного риска развития рака молочной железы. Сегодня женщина может осознанно избежать долгого и непростого лечения, не дожидаясь развития болезни. С помощью современных хирургических технологий удается не только удалить саму ткань молочной железы, но и достичь хорошего эстетического езультата, сохранить сосково-ареолярный комплекс, избавиться от асимметрии, скорректировать форму и размер груди.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Для устранения признаков старения широко применяют нехирургические методы – нитевую имплантологию, аппаратную косметологию и др. Как эти процедуры влияют на структуры лица, не мешают ли они позже хирургическому вмешательству? Оценены результаты SMAS-лифтинга, проведенного авторами после имплантации нитей Aptos в среднюю и нижнюю трети лица. В ранние сроки биодеградации нитей (до 1 года) в ПЖК были обнаружены фрагменты нитей, которые были легко удалены без повреждения сосудов и окружающих структур. В более поздние сроки (12–18 мес.) нити обнаружены не были.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Эстетическая костно-пластическая хирургия лица у людей с ориентальной внешностью кардинально отличается от традиционной хирургии европеоидов. Едва ли не самый важный вопрос, который следует выяснить на консультации, – к каким идеалам стремится пациент, какие культурные традиции поддерживает, какой тип внешности предпочитает. В корне разные подходы. Абсолютно разное планирование, совершенно разные результаты. Подробно описаны некоторые виды операций, выполняемых у пациентов восточной внешности.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Выбрать безопасный филлер с оптимальными реологическими свойствами – основная задача врача-косметолога. Важной характеристикой безопасности филлера служит возможность его ускоренной биодеградации под действием гиалуронидазы. Описаны результаты исследования безопасности применения филлера Novacutan FBio Medium, в ходе которого ученые изучали в динамике скорость его биодеградации путем принудительной ферментации в коже морских свинок.
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
В развитии целлюлита причинно участвуют адипоциты, расположенные у женщин в поверхностном слое жировой ткани ягодично-бедренной области. Слабое воспаление в этой области, скорее всего, вызвано незначительной селективной эндотоксемией, которая может приводить к локальному разрастанию и фиброзу жировой ткани, а также вызывать ее выбухание в дерму, что в совокупности служит характерным признаком целлюлита. Однако значительная эндотоксемия в этой же зоне должна приводить к массивному разрастанию жировой ткани, создавая патофизиологическую основу для липедемы
... Разрушение коллагена и снижение его синтеза при фотостарении приводят к уменьшению прочности и упругости кожи [18]. Снижение содержания коллагена в дерме не только уменьшает эластичность кожи, но и препятствует механическому взаимодействию фибробластов с внеклеточным матриксом, что приводит к формированию порочного круга -снижению активности фибробластов и, как следствие, еще большему снижению количества коллагена в дерме [13,28]. Подобное нарушение структуры и функций компонентов дермы сопрово-ждается появлением внешних признаков старения, таких как морщины и снижение эластичности кожи. ...
Значительное увеличение продолжительности жизни безоговорочно хорошо, однако привело и к тому, что появились новые заболевания, которые мы замечаем в основном у людей преклонного возраста, но формируются они на протяжении всей жизни человека. Описанные простые меры, включающие физическую активность, правильное питание и прием нутрицевтических препаратов, помогут синхронизировать биологический и паспортный возраст, а значит, предупредить заболевания, ассоциированные ссо старением уже здесь и сейчас.
... Aging is a progressive process influenced by both intrinsic and chronological factors and extrinsic or environmental factors which include ultraviolet (UV) rays, air pollution, stress, or smoking [1]. Excessive exposure to UV rays results in the formation of reactive oxygen species (ROS) which causes the adverse effects on the dermal and epidermal connective tissues leading to the damage to cell and cell membranes [2]. ...
Objective: The present study was designed to screen the anti-aging and anti-wrinkle potential of Cucumis sativus fruit through in vitro estimation of antioxidant, anti-hyaluronidase, anti-elastase, anti-collagenase/anti-matrix metalloproteinase (MMP)-1, and anti-tyrosinase activity. Methods: Raw juice of cucumber was taken, filtered and fractionated with ethyl acetate and n-butanol. The obtained extracts were then evaluated for their antioxidant potential through 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay taking ascorbic acid as positive control and other enzymatic activities in reference to hyaluronidase inhibition, MMP-1/collagenase inhibition, and elastase inhibition taking catechin as reference standard whereas for tyrosinase inhibition the standard used was quercetin. Results: All the evaluations were performed in triplicates and results were noted down. It was observed that aqueous extract of C. sativus fruits showed a maximum DPPH radical scavenging activity (p<0.0001), half-maximal inhibitory concentration (IC50) at a concentration of 122.67 μg/ml. The ethyl acetate fraction of C. sativus fruits exhibited maximum hyaluronidase (p<0.0001), MMP-1/collagenase (p<0.04), and tyrosinase (p<0.04) inhibitory activity, IC50 at a concentration of 59.54, 45.79, and 24.46 μg/ml, respectively. The elastase (p<0.0001) inhibitory activity by n-butanol fraction of C. sativus fruits extract was maximum, IC50 at a concentration of 52.76 μg/ml. Conclusion: A potent anti-aging and anti-wrinkle properties were well demonstrated by C. sativus, as depicted from the results obtained.
... Studies on human basement membranes in various tissues have suggested that with advanced age, the strength of the DEJ decreases [3,4]. As the skin ages, the DEJ flattens, which can lead to an approximate 35% decrease in contact between the dermis and epidermis [4][5][6][7]. With age, the fibrils that anchor the various layers of the epidermis to the dermis become stiffer, and skin elasticity decreases due to a fraying of the elastic fibers [8]. ...
Negative pressure wound therapy (NPWT) drape removal from the skin may be painful for patients and inadvertently cause skin damage during the length of therapy. Most NPWT drapes utilize an acrylate adhesive to achieve the seal. To improve the experience associated with NPWT drape removal, a novel hybrid drape was developed. This drape is composed of areas of acrylate adhesive and areas of silicone adhesive. To more fully understand how the removal of the hybrid drape versus the acrylate drape affects the skin, drape removal models were developed to assess the differences in strain profiles for acrylate versus hybrid NPWT drapes using finite element analysis (FEA) to measure the strain and deformation that occurs at the tissue interface with the NPWT drape. The FEA modeling showed that the maximum principal strain associated with the removal of the acrylate drape was 47.3%, whereas the maximum principal strain associated with the removal of the hybrid drape was 21.5%. The average peel force associated with the acrylate drape was 66.1 gf/in, while the peel force for the hybrid drape was 112.5 gf/in. NPWT drape removal may, in certain instances, be related to pain and periwound skin injury. The hybrid drape tested may provide clinicians with an option for NPWT that is gentler for the skin.
... The underlying mechanisms of skin aging are not yet fully understood. The decline in physiological hormones is probably the most important factor contributing to skin aging [159]. Others include UV radiation and the loss of the skin's ability to repair itself (Fig. 12) [160]. ...
The global cosmetics market reached US800 billion by 2023, at around a 7% annual growth rate. The cosmetics industry is emerging as one of the fastest-growing industries of the past decade. Data shows that the Chinese cosmetics market was US450 billion. The influence of social media and the internet has raised awareness of the risks associated with the usage of many chemicals in cosmetics and the health benefits of natural products derived from plants and other natural resources. As a result, the cosmetic industry is now paying more attention to natural products. The present review focus on the possible applications of natural products from various biological sources in skin care cosmetics, including topical care products, fragrances, moisturizers, UV protective, and anti-wrinkle products. In addition, the mechanisms of targets for evaluation of active ingredients in cosmetics and the possible benefits of these bioactive compounds in rejuvenation and health, and their potential role in cosmetics are also discussed.
... Exogenous or extrinsic aging affects most sun exposed areas of the body, while endogenous or intrinsic changes in the characteristics of aging skin are particularly noticeable in areas of the skin that are protected from the sun. 7 Intrinsic aging, reactive oxygen species (ROS) are produced by oxidative metabolism of cells. Exposure to solar radiation also increases the production of ROS and causes damage to DNA, protein, and lipids and reduces antioxidants in the skin.. 1,9 Extrinsic aging, especially caused by UV rays, will also cause an increase in ROS in the dermis. ...
... Loss of dermal collagen is responsible for aging skin's flattened dermo-epidermal interface and disorganized extracellular matrix [43,44]. Li et al., reported that MOTS-c (synthesized, 10 mg/kg, intraperitoneal, 6-week-old mice) increased skin collagen by reducing IL-6, a key inflammatory factor in matrix metalloproteinase 1 (MMP1) and collagen loss in the dermis. ...
MOTS-c, a 16 amino acid mitochondrial derived peptide, is encoded from the 12S rRNA region of the mitochondrial genome. Under stress conditions, MOTS-c translocates to the nucleus where it regulates a wide range of genes in response to metabolic dysfunction. It is colocalized to mitochondria in various tissues and is found in plasma, but the levels decline with age. Since MOTS-c has important cellular functions as well as a possible hormonal role, it has been shown to have beneficial effects on age-related diseases including Diabetes, Cardiovascular diseases, Osteoporosis, postmenopausal obesity and Alzheimer. Aging is characterized by gradual loss of (mitochondrial) metabolic balance, decreased muscle homeostasis and eventual diminished physical capability, which potentially can be reversed with MOTS-c treatment. This review examines the latest findings on biological effects of MOTS-c as a nuclear regulatory peptide and focuses on the role of MOTS-c in aging and age-related disorders, including mechanisms of action and therapeutic potential.
... Thus the advanced age is responsible for the chronological and environmental alterations, which result in an increased risk of disease and At this purpose, telomeres ( Fig. 15.5), which are tandem repeats of DNA sequence and form protective caps of chromosomes, are considered as the marker of both biological aging and cancer development [21]. If shortened, in fact, telomeric DNA is not repaired by the enzyme telomerase and the cell becomes senescent [15,18,21]. Thus short telomere length is associated with earlier death, while its overexpression inhibits aging, increasing tumorigenesis [21]. ...
BACKGROUND
Medical adhesive-related skin injuries (MARSIs) are prevalent adverse effects associated with use of medical devices and increasingly recognized as potentially avoidable. Despite advances in preventive measures, MARSI events still occur, and individualized care must be designed to meet patient needs.
CASES
This article describes three cases where skin injuries occurred because of application, removal, and ongoing use of a medical adhesive device; all three cases occurred underneath dressings used to secure and protect the skin adjacent to a peripherally inserted central catheter (PICC). The first case describes evaluation and management of a skin tear in an elderly female with multiple comorbid conditions, and Case 2 describes assessment and care of contact irritant dermatitis occurring under a PICC dressing. In both cases, specialist nurses with knowledge of MARSI assessed and managed the skin underneath the medical adhesive device in a manner that allowed maintenance of the PICC and continuation of therapy. In contrast, Case 3 describes a female with irritant contact dermatitis underneath a PICC dressing that was responding to care by the nurse specialists of a vascular access team. In this case, the patient presented to their facility’s emergency department with severe itching. The vascular access team initially was not consulted, and the PICC line was removed, although inspection revealed dry skin without signs of infection.
CONCLUSIONS
Medical adhesive-related skin injury is a clinically relevant and useful construct that identifies a variety of prevalent conditions associated with the use of medical adhesive device such as tapes and PICC dressings. These cases, in particular Cases 1 and 2, illustrate that the MARSI construct provides a framework for assessing and managing medical skin injuries with the possibility of preserving the PICC and the ongoing therapy these patients were receiving.
This book is a detailed, evidence-based reference on the field of integrative geriatric medicine. It is intended for all healthcare providers and advocates who work with the geriatric population—in outpatient settings and nursing homes, assisted and independent living facilities, and senior community centers. In addition, it will provide valuable information for leaders and politicians who are involved with implementing policies and procedures for the care of elderly patients and who are looking for safer, less costly, and more patient-centered approaches. Integrative geriatrics is a new field of medicine that advocates for a whole-person, patient-centered, primarily non-pharmacological approach to medical care of the elderly. Most current geriatric practices overprescribe medications and procedures and underutilize non-pharmacological, low-cost, high-touch methods. Patients, however, often show reluctance toward these standard practices because they often involve invasive interventions. The practice of integrative geriatrics is rooted in lifestyle interventions, such as nutrition, movement therapies, and mind-body and spirituality approaches, that allow patients to take a different path to their health, one that utilizes pharmaceuticals and invasive procedures only when safer integrative approaches are not available or not effective.
Background and aim: Botulinum toxin injection is the most popular aesthetic procedure performed worldwide. This cosmetic treatment is used to reduce the appearance of wrinkles and fine lines. Our study aimed to identify the pros and cons of Botox for the anti-aging process. Also, identify the immediate complications and satisfaction level of the patients.
Methodology: We conducted the study in the Department of Dermatology and Venereology, VitaSkin Clinic, Dhaka, Bangladesh. The time period was April 2023 to September 2023. The study design was descriptive cross-sectional. All patients who have come to do Botox in various areas of their body parts at the Department of Dermatology and Venereology of VitaSkin Clinic, Dhaka, were enrolled in the study by purposive sampling. Thereafter, they were scrutinized according to eligibility criteria and 100 patients were finalized. A pre-tested, observation-based, peer-reviewed data collection sheet was prepared before the study. Data regarding clinical, biochemical and surgical profiles were recorded. Data were compiled, edited, and analyzed by SPSS 25.
Results: According to the analysis, this study was conducted by 57 women and 43 men. The number of patients who did their upper face Botox 45, mid face 23 and lower face 32. The level of immediate complications after taking Botox. By doing multivariant (cross-table) analysis, the study revealed significant values of complications. The results show that bruising (n=13, 22.2%; chi-square-8.58, p=0.01), dizziness (n=11, 18.7%; chi-square-6.54, p=0.01), headaches (n=5, 9.6%; chi-square-7.04, p=0.01), swelling (n=9, 20.6%; chi-square-5.28, p=0.01), temporary Muscle weakness (n=7, 18.7%; chi-square-8.12, p=0.01), tears or hollowness under the eyes (n=5, 7.4%; chi-square-6.89, p=0.01) are the immediate complications after doing Botox. Above 93% of patients were satisfied with their treatment.
Conclusion: Botulinum Toxin (Botox) is the most effective anti-aging treatment, where complication is less and satisfaction is high.
Background
Seed oils have been exploited for an array of purposes with their addition to dietary, cosmetics, or therapeutic products. The process of skin aging is a natural and complex phenomenon in living beings. Skin aging is classified into two independent processes, i.e., chronological aging and premature aging. Aging is observed as a loss of strength and elasticity of the skin, leading to wrinkles on the skin. It is due to a decrease in various components of the skin matrix, like elastin, collagen, and hyaluronic acid. Furthermore, aging is potentiated by excessive exposure to UV radiation (Photoaging) and can be prevented or reduced by using products that combat photoaging.
Objective
Anti-aging and antiwrinkle agents are in demand for maintaining skin tone. Seed oils composed of polyunsaturated fatty acids are traditionally used in cosmetic products as moisturizers and emollients, while palmitic acid and oleic acid are known for their penetration-enhancing effect. With the changing trend for extraction of oils like cold pressed methods, seed oils enriched with polyphenols, flavonoids, carotenoids, and phytosterols are good antioxidants and antimicrobials and therefore have an ever-growing demand for their usage in the treatment of skin diseases. In this review, an attempt will be made to brief the phytoconstituents present in various seed oils and their utilization against skin ailments. Furthermore, a mechanistic approach towards the benefit of oils in skin barrier repair, antiaging, and photo-aging with the help of extensive well-designed clinical trials carried out in the recent past is elaborated.
Method
A literature search in the Scopus database, Pubmed, and Medline was carried out using the terminology “aging, photoaging, antioxidant, UV-protection, sunscreens, skin barrier repair, and fatty acids, formulations” in the study. Data were retrieved over the last twenty years.
Result
The review summarises the mechanistic approach and beneficial application of seed oils for healthy and glowing skin. The oils obtained from olives, sesame, borage, grape seeds, and carrot seeds have multitargeted effects. However, the variation in pharmacological effect may vary based on geographically differing varieties, skin type, and person-to-person variation. The need to standardize the varieties for their phytoactive ingredients and the composition of formulation used for skin care can help utilize the seeds as a potential source of actives against skin diseases.
Conclusion
Conclusion: The potential of seed oils can be increased with appropriate analytical tools, validation protocols, and systematic experimental studies at preclinical and clinical trials for their application to skin care products.
Endogenous and exogenous factors can alter the skin layer and appearance, determining skin aging. The extracts and isolated molecules from food matrixes can be used to formulate "healthy" antiaging cosmetics. Two different cosmetic approaches can be used to achieve the antiaging effect. It is possible to use topical products based on food extract (cosmeceutical approach) or take a food supplement and apply a topical cosmetic product based on food extract on the surface to be treated (nutricosmetic approach). This work evaluated in vivo the antiaging potential of a nutricosmetic formulation (cream + food supplement) and a cosmeceutical cream based on Curcuma. The choice of the commercial Curcuma extract to be used for experimental purposes was based on the curcuminoid content determined by an HPLC test. Curcuminoids are the bioactive compounds responsible for Curcuma's antioxidant and antiinflamma-tory properties. Their levels in Curcuma extracts vary according to the storage condition , variety, and pedoclimatic cultivation conditions. The Tewameter ® TM300 was used to evaluate the Trans Epidermal Water Loss (TEWL), the Corneometer ® CM 825 to determine the moisturizing effect, the Cutometer ® to estimate the skin firmness and elasticity, the Dermascan to assess the collagen index, and the Visioface ® 1000D to evaluate the wrinkles. The nutricosmetic product showed potential as moisturizing , anti-age, and anti-wrinkle action better than the cosmeceutical product alone. K E Y W O R D S curcuminoid dosage, food cosmetic, HPLC, moisturizing effect, skin elasticity, skin firmness, spices analysis, TEWL, wrinkles decrease
Aging remains a primary risk factor for a host of diseases, including leading causes of death. Aging and associated diseases are inherently multifactorial, with numerous contributing factors and phenotypes at the molecular, cellular, tissue, and organismal scales. Despite the complexity of aging phenomena, models currently used in aging research possess limitations. Frequently used in vivo models often have important physiological differences, age at different rates, or are genetically engineered to match late disease phenotypes rather than early causes. Conversely, routinely used in vitro models lack the complex tissue-scale and systemic cues that are disrupted in aging. To fill in gaps between in vivo and traditional in vitro models, researchers have increasingly been turning to organotypic models, which provide increased physiological relevance with the accessibility and control of in vitro context. While powerful tools, the development of these models is a field of its own, and many aging researchers may be unaware of recent progress in organotypic models, or hesitant to include these models in their own work. In this review, we describe recent progress in tissue engineering applied to organotypic models, highlighting examples explicitly linked to aging and associated disease, as well as examples of models that are relevant to aging. We specifically highlight progress made in skin, gut, and skeletal muscle, and describe how recently demonstrated models have been used for aging studies or similar phenotypes. Throughout, this review emphasizes the accessibility of these models and aims to provide a resource for researchers seeking to leverage these powerful tools.
Differences between early and late passage cell cultures on the organelle and macromolecular levels have been attributed to cellular "aging". However, concern has been expressed over whether changes in diploid cell populations after serial passage in vitro accurately reflect human cellular aging in vivo. Studies were therefore undertaken to determine if significant differences would be observed in the in vitro lifespans of skin fibroblast cultures from old and young normal, non-hospitalized volunteers and to examine if parameters that change with in vitro "aging" are altered as a function of age in vivo. Statistically signigificant (P less than 0.05) decreases were found in the rate of fibroblast migration, onset of cell culture senescence, in vitro lifespan, cell population replication rate, and cell number at confluency of fibroblast cultures derived from the old donor group when compared to parallel cultures from young donors. No significant differences were observed in modal cell volumes and cellular macromolecular contents. The differences observed in cell cultures from old and young donors were quantitatively and qualitatively distinct from those cellular alterations observed in early and late passage WI-38 cells (in vitro "aging"). Therefore, although early and late passage cultures of human diploid cells may provide an important cell system for examining loss of replicative potential, fibroblast cultures derived from old and young human donors may be a more appropriate model system for studying human cellular aging.
When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite replicative capacity is explained by the chronological age of the donor. Because we had previously shown that telomeres, the terminal guanine-rich sequences of chromosomes, shorten throughout the life-span of cultured cells, we wished to determine whether variation in initial telomere length would account for the unexplained variation in replicative capacity. Analysis of cells from 31 donors (aged 0-93 yr) indicated relatively weak correlations between proliferative ability and donor age (m = -0.2 doubling per yr; r = -0.42; P = 0.02) and between telomeric DNA and donor age (m = -15 base pairs per yr; r = -0.43; P = 0.02). However, there was a striking correlation, valid over the entire age range of the donors, between replicative capacity and initial telomere length (m = 10 doublings per kilobase pair; r = 0.76; P = 0.004), indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. These observations suggest that telomere length is a biomarker of somatic cell aging in humans and are consistent with a causal role for telomere loss in this process. We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. In contrast, telomeres from sperm DNA did not decrease with age of the donor, suggesting that a mechanism for maintaining telomere length, such as telomerase expression, may be active in germ-line tissue.
Biochemical techniques have been used to measure ultraviolet-B (UVB)-induced changes in dermal collagen composition. Hairless albino mice were irradiated dorsally with a daily dose of 62 mJ/cm2 UVB for 12, 24, 30, and 36 weeks. Nonirradiated controls were housed under identical conditions. Additional groups were irradiated for similar periods and kept for a further 6-24 weeks without irradiation. Skin samples were taken from dorsal and ventral (nonirradiated) surfaces and types I and III collagen were quantified densitometrically after cyanogen bromide digestion and polyacrylamide gel electrophoresis. Type III collagen was expressed as a percentage of the total types I and III collagen and the ratio of dorsal/ventral type III (D/V III) was determined for each mouse. The ratio increased significantly in irradiated animals whereas it decreased in the corresponding period in control animals. In irradiated mice withdrawn from UV exposure the ratio D/V III tended to revert to control levels. These data are in agreement with those of our previous human studies, which showed an increase in type III collagen in sun-exposed skin when compared with covered sites.
Damage to skin collagen and elastin (extracellular matrix) is the hallmark of long-term exposure to solar ultraviolet irradiation, and is believed to be responsible for the wrinkled appearance of sun-exposed skin. We report here that matrix-degrading metalloproteinase messenger RNAs, proteins and activities are induced in human skin in vivo within hours of exposure to ultraviolet-B irradiation (UVB). Induction of metalloproteinase proteins and activities occurred at UVB doses well below those that cause skin reddening. Within minutes, low-dose UVB upregulated the transcription factors AP-1 and NF-kappa B, which are known to be stimulators of metalloproteinase genes. All-trans retinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction. We propose that elevated metalloproteinases, resulting from activation of AP-1 and NF-kappa B by low-dose solar irradiation, degrade collagen and elastin in skin. Such damage, if imperfectly repaired, would result in solar scars, which through accumulation from a lifetime of repeated low-dose sunlight exposure could cause premature skin ageing (photoageing).
Long-term solar irradiation produces both morphologic and functional changes in affected skin. Because collagen is the major structural component of skin, any alteration in its production or degradation could have profound effects on cutaneous functional integrity.
Our purpose was to investigate alterations in the production and morphology of collagen fibers brought about by long-term sun exposure.
We compared collagen and collagenase gene expression and collagen immunohistochemical staining and used confocal laser scanning microscopy for morphologic examination of dermal collagen fibers in photodamaged compared with sun-protected skin from the same persons.
Despite a large increase in elastin messenger RNA in sun-damaged skin, collagen and collagenase gene expression remained essentially unchanged. However, striking alterations in the papillary dermis of photoaged skin were found, which revealed large, abnormally clumped elastic fibers and deformed collagen fibers of various diameters, replacing the normal architecture of the papillary dermis.
Our data provide evidence for normal collagen gene expression in sun-damaged skin and suggest that degradation and remodeling of collagen take place in the papillary dermis accompanied by deposition of other matrix components, predominantly abnormal elastic fibers.
Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence.
It has been proposed that telomere shortening is the molecular clock that triggers senescence. To test this hypothesis, two
telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with
vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited
telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced
staining for β-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype
and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between
telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful
state could have important applications in research and medicine.
The skin is increasingly exposed to ambient UV-irradiation thus increasing its risk for photooxidative damage with longterm detrimental effects like photoaging, which is characterized by wrinkles, loss of skin tone, and resilience. Photoaged skin displays prominent alterations in the cellular component and the extracellular matrix of the connective tissue with an accumulation of disorganized elastin and its microfibrillar component fibrillin in the deep dermis and a severe loss of interstitial collagens, the major structural proteins of the dermal connective tissue. The unifying pathogenic agents for these changes are UV-generated reactive oxygen species (ROS) that deplete and damage non-enzymatic and enzymatic antioxidant defense systems of the skin. As well as causing permanent genetic changes, ROS activate cytoplasmic signal transduction pathways in resident fibroblasts that are related to growth, differentiation, senescence, and connective tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in biochemical and clinical characteristics of photoaging. In addition, the relationship of photoaging to intrinsic aging of the skin will be discussed. A decrease in the overall ROS load by efficient sunscreens or other protective agents may represent promising strategies to prevent or at least minimize ROS induced photoaging.
Progressive damage to mitochondrial DNA (mtDNA) during life is thought to contribute to aging processes. However, this idea has been difficult to reconcile with the small fraction of mtDNA so far found to be altered. Here, examination of mtDNA revealed high copy point mutations at specific positions in the control region for replication of human fibroblast mtDNA from normal old, but not young, individuals. Furthermore, in longitudinal studies, one or more mutations appeared in an individual only at an advanced age. Some mutations appeared in more than one individual. Most strikingly, a T414G transversion was found, in a generally high proportion (up to 50 percent) of mtDNA molecules, in 8 of 14 individuals above 65 years of age (57 percent) but was absent in 13 younger individuals.
Background: Long-term solar irradiation produces both morphologic and functional changes in affected skin. Because collagen is the major structural component of skin, any alteration in its production or degradation could have profound effects on cutaneous functional integrity. Objective: Our purpose was to investigate alterations in the production and morphology ofcollagen fibers brought about by long-term sun exposure. Methods: We compared collagen and collagenase gene expression and collagen immunohistochemical staining and used confocal laser scanning microscopy for morphologic examination of dermal collagen fibers in photodamaged compared with sun-protected skin from the same persons. Results: Despite a large increase in elastin messenger RNA in sun-damaged skin, collagen and collagenase gene expression remained essentially unchanged. However, striking alterations in the papillary dermis of photoaged skin were found, which revealed large, abnormally clumped elastic fibers and deformed collagen fibers of various diameters, replacing the normal architecture of the papillary dermis. Conclusion: Our data provide evidence for normal collagen gene expression in sun-damaged skin and suggest that degradation and remodeling of collagen take place in the papillary dermis accompanied by deposition of other matrix components, predominantly abnormal elastic fibers.
Messenger RNA levels were measured in actively dividing fibroblasts isolated from young, middle-age, and old-age humans and
humans with progeria, a rare genetic disorder characterized by accelerated aging. Genes whose expression is associated with
age-related phenotypes and diseases were identified. The data also suggest that an underlying mechanism of the aging process
involves increasing errors in the mitotic machinery of dividing cells in the postreproductive stage of life. We propose that
this dysfunction leads to chromosomal pathologies that result in misregulation of genes involved in the aging process.
Through its anabolic, lipolytic and antinatriuretic actions, GH has profound effects on body composition. In untreated acromegaly, body weight, body cell mass and extracellular water are increased simultaneously with a decrease of body fat. After successful treatment, extracellular water and body fat normalize, but cell mass remains high. The changes in cell mass, body fat and extracellular water observed in acromegaly suggest different dose-response relationships between GH and these parameters. The relationship between GH concentration and the lipolytic actions of GH is more linear, while the relationship between GH and excess extracellular water is more curvilinear. The sodium-retaining effect of GH seems to be mediated by stimulation of the Na+-K+ pump. At higher GH levels, the pump activity is counteracted by an alleged sodium transport inhibitor. In GH-deficient children, GH treatment is followed by rapid loss of adipose tissue and muscular gain. The influence of GH on body composition in GH-deficient adults has recently received attention. Compared to normal subjects, these patients are overweight and have decreased cell mass. Replacement treatment with GH restores body composition towards normal.
The fine structural organization of the epidermis, dermal-epidermal junction, and papillary dermis from unexposed (upper inner arm) and exposed (dorsal forearm) sites of elderly people was compared to the organization of similar regions of young people. Despite an overall thinning of the viable epidermis there was no morphological evidence that the protective function of the epidermis was compromised by age. The differentiation products associated with the keratinization process were not altered in either appearance or amounts in epidermis from unexposed and exposed old skin. Both sites revealed the presence of a well-formed stratum corneum that was the same thickness as that of the young donors. Unexposed and exposed senile skin displayed a relatively flat dermal-epidermal junction devoid of the micro projections of basal cells into the dermis, an indication of a tissue less resistant to shearing forces.Marked elastogenesis, as evidenced by large amounts of 8- to 11-nm (diameter) microfilaments and fibroblasts containing dilated cisternae of rough endoplasmic reticulum filled with flocculent material, was characteristic of the papillary dermis from unexposed and nonactinically damaged exposed old skin. Conversely, in the papillary dermis (Grenz zone) of actinically damaged senile skin the microfilaments were replaced by densely packed collagen fibrils in a colinear arrangement, pre- dominantly parallel to the skin surface. That this dermal architecture was similar to that seen in various scar tissues suggests the Grenz zone is a microscar.
In senescent fibroblast cell lines derived from human embryos, the number of chromosome aberrations were found to increase rapidly. In addition to an increase in aneuploidy and polyploidy, a high frequency of dicentrics occurred, but the number of other chromosome abnormalities remained approximately constant. Banding revealed that many of the dicentrics appeared to be end-to-end fusions of whole chromosomes. The involvement of chromosomes was nonrandom. This "telomeric binding" may reflect a progressive decrease in the stability of telomeric sequences or associated enzymes which may also occur in vivo.
Through its anabolic, lipolytic and antinatriuretic actions, GH has profound effects on body composition. In untreated acromegaly, body weight, body cell mass and extracellular water are increased simultaneously with a decrease of body fat. After successful treatment, extracellular water and body fat normalize, but cell mass remains high. The changes in cell mass, body fat and extracellular water observed in acromegaly suggest different dose-response relationships between GH and these parameters. The relationship between GH concentration and the lipolytic actions of GH is more linear, while the relationship between GH and excess extracellular water is more curvilinear. The sodium-retaining effect of GH seems to be mediated by stimulation of the Na(+)-K+ pump. At higher GH levels, the pump activity is counteracted by an alleged sodium transport inhibitor. In GH-deficient children, GH treatment is followed by rapid loss of adipose tissue and muscular gain. The influence of GH on body composition in GH-deficient adults has recently received attention. Compared to normal subjects, these patients are overweight and have decreased cell mass. Replacement treatment with GH restores body composition towards normal.
In recent years there has been a growing awareness that many of the so-called attributes of aging skin are, instead, a reflection of environmental assault upon exposed areas of the body. Of special import are the deleterious effects of solar radiation on dermal connective tissue, leading to the visible manifestations of photoaging. Often termed "premature aging," the salient features of the process are distinctly different from those found in normal intrinsic aging. In general, chronically irradiated skin is metabolically hyperactive with epidermal hyperplasia and neoplasia, increased production of elastic fibers, GAGs, accelerated breakdown and synthesis of collagen, and enhanced inflammatory processes. In contrast, protected aged skin is usually characterized by a slow decline in many of these components. Experimental studies with animal models have confirmed the notion that the shorter, more energetic portion of the ultraviolet spectrum (UVB) is responsible for the dermal connective tissue destruction observed in photoaged skin. More recently, it has been shown that UVA and infrared radiation contribute significantly to photoaging, producing, among other changes, severe elastosis. Because the three broad wavebands are inseparably linked in terrestrial sunlight, all are of concern in the photoaging of human skin. Photoaged skin has been thought to be irreversibly damaged. However, our findings indicate that destruction and repair go on simultaneously under continued assault by actinic radiation. The balance is shifted toward repair when the radiation stress is relieved. Both epidermis and dermis are capable of moderate self-restoration when exogenous injury ceases, either by avoidance of sunlight or by the use of broad-spectrum, high-SPF sunscreens. Repair of the dermis, characterized by broad regions of new collagen deposited subepidermally, can be pharmacologically enhanced by topical application of retinoic acid. Although early protection from sunlight, before severe photodamage occurs, is most desirable, it is deemed advisable to counsel even older persons with photoaged skin to adopt protective measures, thereby allowing repair processes to occur.
Cutaneous aging represents a complex situation in which at least two independent factors--innate aging and solar exposure--contribute to the development of degenerative changes in the dermis. The biochemical and ultrastructural evidence reviewed in this article indicates that reduced collagen deposition, as a result of diminished collagen biosynthesis and reduced proliferative capacity of the fibroblasts, could explain the development of dermal atrophy and would relate to poor wound healing in the elderly. At the same time, perturbations in the supramolecular organization of the elastic fiber network lead to alterations in the mechanical properties of the skin, as manifested by loose and sagging skin with reduced resilience and elasticity.
In vitro aging models are based on the observation that normal cells in culture have a finite lifespan and eventually cease to proliferate under conditions that initially support excellent growth. Recent assessment of the aging process in keratinocytes, made possible by improved tissue-culture techniques, have confirmed prior findings with fetal and adult fibroblasts and have permitted investigation into the mechanism of in vitro senescence. Early-passage newborn human keratinocytes maintained in a serum-free system were found to proliferate more rapidly than early-passage adult keratinocytes maintained under identical conditions, and they were also found to have far steeper dose-response curves for a potent hypothalamus-derived mitogen keratinocyte growth factor (KGF), as well as for KGF/EGF in combination, with a more than 200-fold increase in cell number, total protein, and colony size over the tested range of concentrations, as opposed to a less than 75-fold increase for adult keratinocytes in these parameters. These results support the hypothesis that the age-associated decrease for keratinocyte proliferation in vitro may be due to progressive loss of mitogenic responsiveness. Unrecognized changes in proliferative rate and growth-factor requirements related to age of the tissue donor may complicate interpretation of studies addressing other aspects of keratinocyte biology.
We studied by light and electron microscopy the microcirculatory vessels in the sun exposed and sun protected skin of normal and psoriatic individuals in order to separate the features of actinic damage from those of chronological aging. In actinically damaged skin, the vascular walls of postcapillary venules and of arterial and venous capillaries were thickened by the peripheral addition of a layer of basement membrane-like material. The veil cells which were intimately related to these layers often had dilated cisternae of rough endoplasmic reticulum containing electron dense material. In 3 of 8 individuals, 70, 70 and 72 yr old, the buttock skin showed mold vascular wall thickening. In 5 other patients, 59-88 yr old the vessels of the buttock skin were normal. In 4 individuals 80-93 yr old, the vessels were abnormally thin (0.5-1.0 micrometer). The veil cells were either absent or decreased in number in these specimens. We propose that (1) the veil cell is responsible for the synthesis and maintenance of the peripheral portion of the vascular wall of the dermal microcirculatory vessels; (2) the veil cell is stimulated to produce excessive basement membrane-like material in response to UV light, factors associated with diabetes mellitus, and possibly to factors associated with the early phase of chronological aging; and (3) with progressive aging there is a decrease in the number and synthetic activity of veil cells which correlates with the appearance of abnormally thin walled vessels.
We studied by light and electron microscopy the elastic fibers in he sun exposed and sun protected skin of normal and psoriatic individuals of different ages in order to separate the changes of actinic damage from those of chronological aging. The sun exposed skin showed 2 types of elastic fiber abnormalities-one related to actinic damage and the other to chronological aging. The sun protected buttock skin showed only the latter. From ages 30 to 70, a minority of the elastic fibers exhibited abnormalities that appeared to represent a process of fiber disintegration. After age 70, the majority of elastic fibers showed these abnormalities. These abnormalities were present without accompanying inflammatory cells. Also, there was morphological evidence of continuing synthesis of elastic fibers during the lifetime of these subjects, except that from ages 50-93, the fibers appeared to be loosely, rather than compactly, assembled. Incubation of dermal slices from buttock skin of young adults with porcine pancreatic elastase and bovine chymotrypsin produced elastic fiber degradation that closely simulated the changes that were observed in aged sun protected skin. We propose that one of the features of cutaneous aging is a slow, spontaneous, progressive degradative process inherent in the elastic fiber that can be enzymatically accelerated from decades to hours by elastase and chymotrypsin.
Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppressive mechanism and an underlying cause of aging. There is ample evidence that escape from senescence, or immortality, is important for malignant transformation. By contrast, the role of replicative senescence in organismic aging is controversial. Studies on cells cultured from donors of different ages, genetic backgrounds, or species suggest that senescence occurs in vivo and that organismic lifespan and cell replicative lifespan are under common genetic control. However, senescent cells cannot be distinguished from quiescent or terminally differentiated cells in tissues. Thus, evidence that senescent cells exist and accumulate with age in vivo is lacking. We show that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture. This marker was expressed by senescent, but not presenescent, fibroblasts and keratinocytes but was absent from quiescent fibroblasts and terminally differentiated keratinocytes. It was also absent from immortal cells but was induced by genetic manipulations that reversed immortality. In skin samples from human donors of different age, there was an age-dependent increase in this marker in dermal fibroblasts and epidermal keratinocytes. This marker provides in situ evidence that senescent cells may exist and accumulate with age in vivo.
Chronic sun exposure induces numerous changes in exposed skin; the most striking histopathologic change is the massive accumulation of material with the staining characteristics of elastin, termed solar elastosis, in the superficial dermis. Previous studies have identified elastic fibers within areas of solar elastosis, as well as a decrease in collagen content. Recently, the large chondroitin sulfate (CS) proteoglycan, versican, has been identified in the dermis in association with elastic fibers, and the smaller CS proteoglycan, decorin, has been shown to codistribute with collagen fibers. Thus, changes in expression of these CS proteoglycans might be expected in photoaging and may help to explain the clinical alterations of chronically sun-exposed skin.
Immunohistochemical staining and confocal laser scanning microscopy for versican and decorin was performed on paired tissue samples from photoaged and non-sun-exposed skin taken from the same individuals. To investigate versican and decorin mRNA expression, Northern analysis was performed on paired fibroblast cultures derived from tissue explants of photoaged and non-sun-exposed skin.
Immunohistochemical staining and confocal laser scanning microscopy revealed a massive accumulation of versican localized to the abnormally large fibers comprising solar elastosis in the superficial and mid-dermis of photoaged specimens. Decorin staining was greatly decreased within the area of solar elastosis. Similarly, changes in mRNA were measured from fibroblast cultures, with a significant increase in versican mRNA in cultures derived from photoaged skin, whereas decorin mRNA levels were significantly decreased in photoaged skin.
This study provides further evidence for the close association of versican with elastic fibers and decorin with collagen fibers, even in the situation of abnormal fiber deposition occurring in photodamaged skin. In addition, changes in versican and decorin immunostaining are accompanied by similar alterations in gene expression.
UVA- and UVB-induced alterations in dermal collagen were investigated in a murine animal model. Groups of hairless mice were exposed to UVA and UVB for 28 weeks at a dose of 60 J/cm2 three times weekly and 0.06 J/cm2 three times weekly, respectively. Untreated animals were used as controls. Every 4 weeks dorsal skin was examined for quantitative and qualitative changes in dermal collagen. Neither UVA nor UVB caused a significant alteration in total skin collagen content. However, after UVA treatment the ability of skin collagen to be digested by pepsin decreased dramatically (up to 65% of skin collagen remained insoluble after 4 months), whereas exposure to UVB had no significant effect. Furthermore a shift in the ratio of alpha 1(I,III) chains to alpha 2(I) chains was detected after UVA exposure. The amount of type V collagen in mouse skin, as determined by a sensitive ELISA method, was markedly decreased after UVA treatment, but not after UVB treatment.
Fractographic techniques based on mathematical morphology were used to study aging-related epidermal changes in abdominal skin samples obtained from 96 autopsy cases. Three linear roughness indices were evaluated for the rete peg profile and the shrinkage effect on the basal layer and interface between the granular and horny layers. Elderly subjects had a 36.3% decrease in rete peg-related roughness index when compared with younger subjects. This roughness index has been corrected, with shrinkage due to skin elasticity taken into account. For females, fitting of a logistic decay function yielded a curve with right and left asymptotes and a steeper descent between 40 and 60 years. Half value time--i.e., the time when half rete peg profile flattening occurred--was 46.8 years. In contrast, males showed almost monotonical decay. Epidermal thickness measured between rete pegs showed the same exponential decline for both sexes, with values from 22.6 to 11.4 microns. Skin shrinkage in elderly subjects decreased 22% in superficial layers and only 6% in the lower epidermis. In both cases shrinkage had a linear relation with age, and no sex differences were found.
Topical tretinoin (retinoic acid) modifies fine wrinkles and certain other features of human skin damaged by exposure to the sun (photodamage), but histologic changes do not account for this improvement. In mice with photodamage induced by ultraviolet light, effacement of fine wrinkles by tretinoin is correlated with dermal collagen synthesis but not with histologic changes. We investigated whether collagen synthesis was reduced in photodamaged human skin and, if so, whether it could be restored by treatment with topical tretinoin.
Biopsies of photodamaged skin from the extensor aspect of the forearm and skin from the buttocks, which had been protected from the sun, were performed on 26 healthy subjects. In addition, 29 patients with photodamaged skin were treated for 10 to 12 months with a daily application of 0.1 percent tretinoin cream (15 patients) or vehicle cream (14 patients). Skin-biopsy specimens obtained at base line and after treatment were assessed immunohistologically for evidence of dermal collagen I formation (collagen synthesis).
Collagen I formation was 56 percent less in the papillary dermis of photodamaged skin than in skin protected from the sun (P < 0.001) and was correlated with the clinical severity of photodamage (r = -0.58, P = 0.002). Treatment of photodamaged skin with tretinoin produced an 80 percent increase in collagen I formation, as compared with a 14 percent decrease in collagen formation with the use of vehicle alone (P = 0.006).
The formation of collagen I is significantly decreased in photodamaged human skin, and this process is partly restored by treatment with tretinoin.
Singlet oxygen generated in a dark reaction by thermodissociation of an endoperoxide (NDPO2) elicits an increase in mRNA of interstitial collagenase (MMP-1) in cultured human fibroblasts. The effect is enhanced in deuterium oxide-based medium and is abolished in the presence of non-toxic doses of sodium azide. In contrast, the mRNA level of the tissue inhibitor of metalloproteinases (TIMP-1) remains unaltered under these experimental conditions. These observations support the suggestion that an unbalanced synthesis of collagenase and TIMP reported to occur following UV-A irradiation or during inflammatory conditions may be mediated by singlet oxygen.
Normal cells have limited proliferative potential in culture, a fact that has been the basis of their use as a model for replicative senescence for many years. Recent molecular analyses have identified numerous changes in gene expression that occur as cells become senescent, and the results indicate that multiple levels of control contribute to the irreversible growth arrest. These include repression of growth stimulatory genes, overexpression of growth inhibitory genes, and interference with downstream pathways. Studies with cell types other than fibroblasts will better define the role of cell senescence in the aging process and in tumorigenesis.
The coincidence of climacteric symptoms and the beginning of skin aging suggests that estrogen deficiency may be a common and important factor in the perimenopausal woman. Often hormones have been considered important in endogenous aging of the skin, but their role has not been clearly defined. Therefore, we investigated, whether topical treatment of the skin with estrogen could reverse some of the changes in the aging skin.
The effects of 0.01% estradiol and 0.3% estriol compounds were compared in 59 preclimacteric women with skim aging symptoms. Monthly determinations of estrodiol (E2), follicle-stimulating hormone (FSH), and prolactin (PRL) were done and the monthly clinical monitoring was supplemented by measurements of skin hydration by corneometry and profilometry. In 10 patients, skin biopsies were taken for immunohistochemical determination of collagen types I and III.
After treatment for 6 months, elasticity and firmness of the skin had markedly improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both groups. Furthermore, skin moisture had increased and the measurement of wrinkles using skin profilometry, revealed significant, or even highly significant, decreases of wrinkle depth in the estradiol and the estriol groups, respectively. On immunohistochemistry, significant increases of Type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. As to hormone levels, only those of PRL had increased significantly and no systemic hormonal side effects were noted.
Chronic sun exposure leads to structural and functional alterations in exposed skin. Photoageing is a process distinct from the changes taking place due to chronological ageing. Unique alterations in the dermal extracellular matrix occur as a result of photoageing and are responsible for many of these physiological changes taking place in sun-damaged skin. Accompanying the deposition of abnormal elastic tissue, or solar elastosis, are significant alterations in dermal glycosaminoglycans (GAGs). Accumulation of GAGs as a result of photoageing, as demonstrated in both humans and animal models of photoageing, seems almost paradoxical in view of the large amounts of GAGs present in the skin of newborns, making their skin well hydrated and supple, in sharp contrast to the weathered appearance of photoaged skin. We investigate the relative GAG content of photoaged skin using immunoperoxidase stains specific for hyaluronic acid and chondroitin sulphate, and determine the location of these GAGs using confocal laser scanning microscopy. Our results demonstrate significant increases in GAG staining in sun-damaged vs. sun-protected skin from the same individuals, as measured by computer-based image analysis. Furthermore, confocal laser scanning microscopy reveals that the increased dermal GAGs in sun-damaged skin are deposited on the elastotic material of the superficial dermis of photodamaged skin, and not between collagen and elastic fibres as in normal skin. The abnormal location of GAGs on these fibres may explain the apparent paradoxical weathered appearance of photodamaged skin despite increased GAGs.
The wavelength dependence for the regulation of two major matrix-metalloproteinases, interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3), and their major inhibitor, tissue inhibitor of metalloproteinases (TIMP-1), was studied in human dermal fibroblasts in vitro. Monochromatic irradiation at 302, 307, 312 and 317 nm with intensities ranging from 20 to 300 J/m2 increased MMP-1 and MMP-3 mRNA steady-state levels and the secretion of the corresponding proteins up to 4.4-fold, whereas almost no increase was observed at wavelengths < 290 nm. In contrast, the synthesis of TIMP-1 increased only marginally. This imbalance may contribute to the severe connective tissue damage related to photoaging of the skin. The wavelengths responsible for MMP-1 and MMP-3 induction reported here are distinct from the absorption spectrum of DNA and are different from results previously reported in the literature. Importantly, they overlap with wavelengths whose intensity is predicted to increase on the earth's surface upon ozone depletion. Intensities and particular wavelengths used in our studies in vitro can be absorbed readily by fibroblasts within the skin in vivo and, thus, are relevant for risk assessment and development of protective agents.
Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging.
We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis.
A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin.
Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.
The important factors for UV sensitivity in humans are considered to be the skin pigmentation and the epidermal thickness. In this study on 73 Caucasians (age 20-85 years), we investigated in UV unexposed buttock skin the relationship between the UV sensitivity and constitutive skin pigmentation and thickness of the stratum corneum and the cellular part of the epidermis, in 34 normal people and in 39 skin cancer patients (20) patients with cutaneous malignant melanoma and 19 patients with basal cell carcinoma of the skin). Skin pigmentation was measured by skin reflectance spectroscopy, and UV sensitivity by phototest with a solar simulator. Thicknesses of the stratum corneum and the cellular part of the epidermis were determined by light microscopic evaluation of skin biopsies from the phototest areas. We found that epidermal thickness was independent of skin type and was not correlated to constitutive skin pigmentation. Thickness of the stratum corneum was statistically not different in normal persons and in skin cancer patients (P = 0.41) and was independent of gender (P = 0.61) and age (P = 0.56), while thickness of the cellular epidermis decreased with age (P < 0.01). Stratum corneum thickness was found to be of minor importance for the constitutive UV sensitivity (accounting for on average 11% of the total photoprotection), which was mainly determined by the constitutive skin pigmentation (goodness-of-fit for correlation r = 0.83). A theoretical model for the relationship of UV dose to induction of clinical erythema grade and skin pigmentation and thickness of the stratum corneum was developed. Objective measurements of skin pigmentation in UV unexposed skin by skin reflectance spectroscopy in Caucasians, normal people and people with cutaneous malignant melanoma and basal cell carcinoma of the skin predicts the constitutive UV sensitivity with a high degree of precision.
The acceleration of fixed-postmitotic cell aging by a high metabolic rate and the age related loss of mitochondria found in that cell type led us to propose an oxygen stress-mitochondrial mutation theory of aging, according to which senescence may be linked to mutations of the mitochondrial genome (mtDNA) of the irreversibly differentiated cells. This extranuclear somatic gene mutation concept of aging is supported by the fact that mtDNA synthesis takes place at the inner mitochondrial membrane near the sites of formation of highly reactive oxygen species. Mitochondrial DNA may be unable to prevent the intrinsic mutagenesis caused by those byproducts of respiration because, in contrast to the nuclear genome, it lacks excision and recombination repair. The resulting mitochondrial impairment and concomitant cell bioenergetic decline may cause the senescent loss of physiological performance and may play a key role in the pathogenesis of many age-related degenerative diseases. These concepts are integrated with classic and contemporary hypotheses in a unitary theory that reconciles programmed and stochastic concepts of aging. Thus, it is suggested that cells are programmed to differentiate, and then they accumulate mitochondrial-genetic damage because of their high levels of oxyradical stress and the loss of the organelle rejuvenating power of mitosis.
Wrinkles are a major topic in dermocosmetology; the purpose of this work has been to go deeper into the knowledge of cutaneous damage underlying these modifications of skin surface. Up to now, the number of published works about the histological structure of wrinkles is not very large. Therefore to complete the findings, we studied 46 subjects of both sexes, between 57 and 98-year-old, enabling us to obtain 157 skin biopsies of wrinkles (face) and sun-protected areas (abdomen). We used different histological techniques involving histochemistry, immunohistochemistry, electron microscopy and quantification by image analysis in addition to classic standard techniques. This study has allowed us to confirm published structural modifications of wrinkles, but also to display many other original alterations. The increased thinning of the epidermis atrophied with age is confirmed by the study of desmoplakins outlining the cellular contours of keratinocytes. Such a thinning is accompanied by a decrease in several markers of epidermal differentiation at the bottom of the wrinkles: filaggrin, keratohyalin granules and transglutaminase I, disturbing desquamation and the capacity of the horny layer to retain water. The dermoepidermal junction is modified by a decrease of collagen IV and VII, which, combined with fewer and fewer oxytalan fibres under wrinkles, weakens this interface. The deposition of abnormal elastotic tissue in the dermis, with an interruption of these deposits under wrinkles and an atrophy of dermal collagen more pronounced under wrinkles, boosts the magnitude and depth of wrinkles. The composition of the other dermal constituents is also altered with, more particularly, a marked decrease of chondroitin sulphates in the papillary dermis under wrinkles, combined with an asymmetrical variation of glycosaminoglycans on both edges of wrinkles. The atrophy of the hypodermis, also more marked under wrinkles, with a thickening of fibrous lines, also makes the depth of wrinkles more pronounced. Wrinkle formation appears at the same time as numerous modifications in different cutaneous structures, which may be mutually amplified. Such a study by pointing out altered elements in skin physiology, makes the development of specific treatments possible in order to mitigate this unwelcome cutaneous deterioration.
Degenerative processes of elastic fibers in sun-protected and sun-exposed skin were analyzed by light and electron microscopic (post-embedding) immunocytochemistry using antisera to elastin, fibrillin-1, amyloid P component, lysozyme and alpha1-antitrypsin. To assess the effect of aging and sun exposure, biopsy specimens of sun-protected skin (back) and severely and moderately sun-exposed skin (face and forearms) were obtained from a young age group (1-27 years), an adult group (31-56 years) and an old aged group (61-100 years). Elastin and fibrillin-1 were the essential components of elastic fibers; elastin being localized in the electron-lucent matrix and fibrillin-1 in the dense microfibrillar strands. Aging and sun exposure provoked degenerative condensed spots, which represented widened dense microfibrillar strands, in the matrix of altered elastic fibers in the reticular dermis. Amyloid P component was first deposited on the peripheral microfibrils, and then in the intermediate density zone of the spots. Lysozyme was observed in both the electron-dense core and in the intermediate density zone of the spots. Deposition of lysozyme correlated with basophilic degeneration of the elastic fibers. In the severely photodamaged facial skin of the aged, which showed solar elastosis in the upper reticular dermis, fibrillin-1 immunoreactivity was lost from the thickened and vacuolated elastic fibers that lacked condensed spots, and amyloid P component, lysozyme and alpha1-antitrypsin were diffusely deposited in the elastin-positive matrix. It seemed that amyloid P component deposition on the elastic fibers was closely associated with aging, while immunoreactive lysozyme was related to sun exposure. Vertically oriented, thin, elastic (oxytalan) fibers in the papillary dermis tended to decrease with age, with frequent deposition of amyloid P component but no lysozyme. In the facial skin of the aged, dermal papillae disappeared, with the formation of degenerative elastic globules beneath the dermal-epidermal junction. The present study demonstrated an intimate relationship between ultrastructural alterations and deposition of exogenous substances on the degenerative elastic fibers in sun-exposed and/or aged skin.
Solar elastosis is a hallmark of photoaged human skin and a prominent feature in experimentally produced photoaging in murine skin. The products of mast cells have been implicated in the development of photoaged skin. We evaluated whether products from mast cells mediate chronic UVB-induced changes in murine skin by employing a strain of mast cell-deficient mice, WWv. The responses in these mice were compared to those in BALB/c, another albino mouse strain. Mice were exposed three times per week to UVB radiation for 11 weeks; the total dose was 18.8 J/cm2. Irradiated WWv mice showed greater epidermal alterations than the irradiated BALB/c mice. In the dermis, a 3.6-fold increase in elastin content, as measured by desmosine, was produced in the UVB-treated BALB/c mice; in contrast, no difference was observed in elastin between UVB-treated and untreated WWv mice. Collagen content was not increased by UVB treatment in either strain, and the glycosaminoglycan content increased a similar amount in UVB-treated mice in both strains. The number of mast cells increased two-fold and the number of neutrophils increased six-fold in UVB-treated BALB/c mice compared to age-matched unirradiated controls. Neutrophils, as well as mast cells, were absent in untreated and UVB-treated WWv mouse skin. These results suggest that products of mast cells are important in the development of solar elastosis in murine skin either by directly inducing elastin production by fibroblasts or indirectly by mediating the presence of other cell types that produce products that increase fibroblast elastin production.
Progressive damage to mitochondrial DNA (mtDNA) during life is thought to contribute to aging processes. However, this idea has been difficult to reconcile with the small fraction of mtDNA so far found to be altered. Here, examination of mtDNA revealed high copy point mutations at specific positions in the control region for replication of human fibroblast mtDNA from normal old, but not young, individuals. Furthermore, in longitudinal studies, one or more mutations appeared in an individual only at an advanced age. Some mutations appeared in more than one individual. Most strikingly, a T414G transversion was found, in a generally high proportion (up to 50 percent) of mtDNA molecules, in 8 of 14 individuals above 65 years of age (57 percent) but was absent in 13 younger individuals.
The aim of our study was to evaluate the effect of aging and postmenopausal hypoestrogenism on skin collagen content.
Thirty-two women (mean age 48.78 +/- 9.86; year +/- S.D., range 28-68), 14 in premenopause and 18 in postmenopause, underwent skin biopsies performed during laparotomic operation. The amount of collagen type I, III and type III/type I ratio was evaluated by immunohistochemistry and computerised image analysis, and was related to age and years of postmenopause.
In the postmenopausal patients, a significant (P < 0.01) decrease of percentage of skin collagen type I, type III and type III/type I ratio was observed in comparison to premenopausal women. The percentages of collagen type I, type III and type III/I ratio of all patients studied was significantly (P < 0.01) correlated with chronological age (r = 0.88, 0.89 and 0.61, respectively). Considering only postmenopausal subjects, the correlation with chronological age was significant (P < 0.01) for collagen type I and type III of postmenopausal women (r = 0.59, r = 0.64, respectively), but not for the type III/I ratio (r = 0.37, P = 0.131). The percentages of collagen type I, type III and type III/I ratio of postmenopausal women showed a significant (P < 0.01) inverse correlation with years of postmenopause (r = 0.76, 0.73 and 0.73, respectively).
Our data suggest that the decrease of skin collagen is an estrogen-related phenomenon.