Skin Aging Research Articles

Lactate triggers KAT8-mediated LTBP1 lactylation at lysine 752 to promote skin rejuvenation by inducing collagen synthesis in fibroblasts

Decreased collagen synthesis by fibroblasts is a key aspect of skin aging. Poly-L-Lactic Acid (PLLA) is a bioabsorbable material that can release lactate continuously, stimulating endogenous collagen synthesis in the skin. Herein, this study aimed to investigate the impact of PLLA-released lactate on collagen production in fibroblasts for skin rejuvenation. Human fibroblasts were exposed to varying concentrations of PLLA in vitro, while PLLA was injected into the back skin of aged mice in vivo. Safety and efficacy of PLLA on collagen synthesis and skin rejuvenation were evaluated through Calcein-AM/PI staining, EdU proliferation assay, and analysis of collagen I and collagen III expression in fibroblasts using western blotting and immunofluorescence. To elucidate the underlying mechanisms, lactate contents in cell-free supernatant and cell lysates from PLLA-treated fibroblasts, as well as total lysine lactylation (Pan Kla) levels were measured. Additionally, we found that fibroblasts can uptake extracellular lactate released from PLLA through monocarboxylate transporter-1 (MCT1) to facilitate latent-transforming growth factor beta-binding protein 1 (LTBP1) lactylation at lysine 752 (K752) via a KAT8-dependent mechanism, then increases the protein levels of collagen I and collagen III in fibroblasts. Overall, this study highlights a valuable insight into lactylation modification of non-histone protein for skin rejuvenation.

Assessment of the Effect of Berberine on Metalloprotease Enzymes Inhibition and Antioxidant Activity: Possible Application in Skin Aging

Assessment of the Effect of Berberine on Metalloprotease Enzymes Inhibition and Antioxidant Activity: Possible Application in Skin Aging

Carnosine and Retinol Synergistically Inhibit UVB-Induced PGE2 Synthesis in Human Keratinocytes through the Up-Regulation of Hyaluronan Synthase 2.

Skin aging results from complex interactions of intrinsic and extrinsic factors, leading to structural and biochemical changes such as wrinkles and dryness. Ultraviolet (UV) irradiation leads to the degradation of hyaluronic acid (HA) in the skin, and the with fragmented HA contributes to inflammation. This study revealed that the synergistic combination of carnosine and retinol (ROL) increases HA production in normal human epidermal keratinocytes (NHEKs) by upregulating hyaluronan synthase 2 (HAS2) gene transcription. Simultaneously, the combined treatment of carnosine and ROL significantly attenuates UVB-induced prostaglandin E2 (PGE2) synthesis in NHEKs. A significant correlation exists between the increase of HA synthesis and the inhibition of PGE2 production. This study suggested that combined treatment of carnosine and ROL can improve skin aging phenotypes associated with UVB irradiation.

Beyond the genome: protecting the proteome may be the key to preventing skin aging.

Skin aging is associated with a progressive decline in physiological functions, skin cancers and, ultimately, death. It may be categorized as intrinsic or extrinsic, whereby intrinsic aging is attributed to chronological and genetic factors. At the molecular level, skin aging involves changes in protein conformation and function. The skin proteome changes constantly, mainly through carbonylation; an irreversible phenomenon leading to protein accumulation as toxic aggregates that impair cellular physiology and accelerate skin aging. This review details the central role of proteostasis during skin aging and why proteome protection may be a promising approach in mitigating skin aging. A comprehensive literature review of 87 articles focusing on the proteome, proteostasis, proteotoxicity, protein carbonylation, and the impact of the damaged proteome on aging, and in particular skin aging, was conducted. Skin aging is associated with deficiencies in the repair mechanisms of DNA, transcriptional control, mitochondrial function, cell cycle control, apoptosis, cellular metabolism, changes in hormonal levels secondary to toxicity of damaged proteins, and cell-to-cell communication for tissue homeostasis, which are largely controlled by proteins. In this context, a damaged proteome that leads to the loss of proteostasis may be considered as the first step in tissue aging. There is growing evidence that a healthy proteome plays a central role in skin and in maintaining healthy tissues, thus slowing down the process of skin aging. Hence, protecting the proteome against oxidative or other damage may be an appropriate strategy to prevent and delay skin aging.

The Characteristics and Inheriting Pattern of Skin Aging in Chinese Women: An Intergenerational Study of Mothers and Daughters.

The aging of the skin, which is affected by both external and internal causes, can reflect the external age and the internal health status. While the aging characteristics differ across ethnic groups, the specific changes in skin aging within the Chinese population have been underexplored. Moreover, investigating the similarity of aging skin characteristics between parent-offspring pairs remains uncharted territory. This study aims to fill these gaps by examining the skin aging features of Chinese women and assessing the similarity in aging skin characteristics between mother-daughter pairs. A total of 40 mother-daughter pairs were recruited and analyzed. The perceived ages of the participants were evaluated, and their aging skin traits were systematically graded. Statistical methods were employed to discern the trends of the aging skin characteristics. By introducing a novel similarity parameter, we compared whether various skin aging characteristics have similar patterns between mothers and daughters. Our findings indicate that age 50 represents a pivotal point in skin aging. Beyond this age, the increase in rhytides and laxity scores accelerated noticeably, whereas the escalation in dyschromia scores became less marked. By introducing similar parameters between mother-daughter pairs and the radar map, we discovered that the skin aging characteristics are remarkably consistent between mother-daughter pairs. Understanding the main aging skin characteristics of different age groups can allow caregivers to devise treatments for preventing skin aging in women of various ages. The mother's skin aging trend is also significant for the daughter's skin aging prevention.

Skin Rejuvenation in Aged Mice by Fecal Microbiota Transplantation from Young Mice Feces

Skin aging is an increasingly prominent topic in the context of healthy aging. During the aging process, the skin’s barrier function diminishes, its water content decreases, wrinkles begin to form, and changes occur in the gut microbiota composition. However, the relationship between gut microbiota and skin aging remains unclear. In this study, we explored skin rejuvenation in aged mice through fecal microbiota transplantation (FMT) using feces from young mice. The results demonstrated enhanced water retention, thickened stratum corneum, increased collagen content, and improved epithelial cell differentiation in aged mice following FMT. Notably, FMT particularly increased the abundance of Lactobacillus and Lactococcus in aged mice, which were nearly undetectable in untreated aged mice. Non-targeted and targeted metabolomics analyses indicated that FMT significantly elevated levels of tryptophan (Trp) and its microbiota metabolites (e.g., indole-3-lactic acid (ILA)) in the feces and serum of aged mice. Both Trp and ILA appeared to rejuvenate aged skin by activating the aryl hydrocarbon receptor (AhR) to promote epidermal cell differentiation. In conclusion, FMT from young mice rejuvenated aged skin via Trp-metabolizing bacteria (Lactobacillus and Lactococcus) and Trp-derived metabolites, suggesting that interventions targeting Trp metabolites may effectively improve skin aging.

Synthesis of 7,8-dihydroxy-4-phenylbenzo[g]coumarins as potential multitarget anti-skin-aging candidates

Skin aging is a gradual, spontaneous, slow-processing, and natural phenomenon that induces a negative impact on the skin's function and structure. Numerous cosmoceutical products have been studied for their ability to prevent skin aging. However, only one published study looked into these coumarin-related traits. This research gap stimulated the initiation of the present work, in which six 4-phenyldihydroxybenzocoumarins were synthesized starting from 2,3,6-triaminonaphthalene. The latter was transformed into a diazonium salt product that undergoes a Sandmeyer reaction, forming 2,3,6-trihydroxynaphthalene. This multihydroxylated compound is coupled with various ethyl benzoylacetate derivatives to yield the target compounds coded YR1-YR6. By analyzing the FTIR, 1HNMR , 13CNMR , and HRMS spectra, the molecular structures of the synthesized coumarins were confirmed. The anti-skin-aging potential was evaluated by following the inhibitory properties of these compounds against four skin aging-related enzymes, which are tyrosinase, elastase, collagenase, and hyaluronidase. Also, the inhibitory behavior profiles were defined by plotting Lineweaver-Burk diagrams. To detect whether they are normal-skin biocompatible, the compounds under investigation were tested using a human skin keratinocyte line. The results showed that the synthesized coumarins demonstrated outperforming inhibitory properties against the test four enzymes exceeding those of references used. Also, the inhibitory behaviors of the synthesized coumarins were collectively detected as competitive inhibitors against enzymes under study. Regarding the skin biocompatibility, these compounds showed excellent biosafety profiles toward the keratinocytes studied. Given the results, the general framework of the synthesized coumarins, 7,8-dihydroxy-4-phenylbenzo[g]coumarin, is responsible for the superior anti-skin-aging effects. On the other hand, the para substitution on the phenyl ring exerts a detected but minor role in these effects. The author concluded that the skeletons of the synthesized coumarins provide insights to develop potential multitarget anti-skin-aging biocompatible candidates. Also, there is a good opportunity for YR1 and YR2 to be directly included in the pre-clinical studies, minimizing the time spent considering them as anti-skin medications.

Natural active ingredients in cosmetics for mature skin

The human skin performs key functions in the human body, while also being a reflection of the many changes occurring within it. The face, which is most exposed to external factors, is the area where the skin ageing process progresses most rapidly. The study aimed to review the most commonly used active ingredients in natural cosmetics for mature skin, available on the Polish cosmetics market. Raw materials of natural origin are a rich source of active substances, which are widely used in cosmetics. These substances not only moisturise, nourish, cleanse, soften and smooth the skin, but also stimulate circulation in blood vessels, eliminating redness and swelling. The use of active ingredients of natural origin can effectively maintain mature skin in good condition, significantly delaying the ageing processes occurring within it.

Skin inflammatory signatures, as measured by disordered spatial redness patterns, predict current and future skin ageing attributes.

Facial skin redness can be an indicator of skin inflammation, however the physiological connection between facial redness and inflammatory status, as well as its role in age-related skin changes, remains poorly understood. This study aims to investigate the association between the pattern of facial skin redness and biological inflammatory status, as well as age-related changes occurring in the skin. Four studies were conducted recruiting healthy Northern Asian females. Disordered spatial patterns of facial skin redness signals were assessed using image analysis, i.e., the a* gradient algorithm, which quantifies the disordered shape and pattern of localized redness signals on facial skin. This redness pattern was compared with (1) inflammatory protein markers (IL-1Ra/ IL-1α and IL-8) measured from stripped corneocyte samples, (2) gene expression profiles obtained through transcriptome analysis using skin biopsy samples, and (3) the distribution pattern of blood vessel measured using a photoacoustic microscope. The association between the skin redness pattern and current and future ageing-related skin changes was examined through a longitudinal study tracking the same subjects for 10 years. A significant correlation was observed between the a* gradient and the levels of inflammatory cytokines (IL-1Ra/IL-1α and IL-8). Transcriptome analysis revealed upregulation of genes related to acute inflammation, chronic inflammation, cellular senescence, and angiogenesis in subjects with higher a* gradients. The high a* gradient group exhibited an extension of blood vessel diameter and increased blood vessel density, while the medium a* gradient group only exhibited blood vessel extension. Lastly, the 10-year longitudinal study demonstrated that the a* gradient was associated with current and future skin ageing-related attributes, such as increased skin texture and wrinkle formation. The spatial pattern of localized redness on the skin reflects the biological inflammatory status, and this inflammatory condition helps predict current and future age-related skin changes.

Regulatory Mechanisms of Natural Active Ingredients and Compounds on Keratinocytes and Fibroblasts in Mitigating Skin Photoaging.

The mechanism underlying skin photoaging remains elusive because of the intricate cellular and molecular changes that contribute to this phenomenon, which have yet to be elucidated. In photoaging, the roles of keratinocytes and fibroblasts are vital for maintaining skin structure and elasticity. But these cells can get photo-induced damage during photoaging, causing skin morphological changes. Recently, the function of natural active ingredients in treating and preventing photoaging has drawn more attention, with researches often focusing on keratinocytes and fibroblasts. We searched for studies published from 2007 to January 2024 in the Web of Science, PubMed, and ScienceDirect databases through the following keywords: natural plant, natural plant products or phytochemicals, traditional Chinese Medicine or Chinese herbal, plant extracts, solar skin aging, skin photoaging, and skin wrinkling. This review conducted the accordance of Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. In total, 87 researches were included in this review (Figure 1). In keratinocytes, natural compounds may primarily regulate signal pathways such as the NF-κB, MAPK, PI3K/AKT, and Nrf2/ARE pathways, reducing inflammation and cellular damage, thus slowing skin photoaging. Additionally, in fibroblasts, natural active ingredients primarily promote the TGF-β pathway, inhibit MMPs activity, and enhance collagen synthesis while potentially modulating the mTOR pathway, thereby protecting the dermal collagen network and reducing wrinkle formation. Several trials showed that natural compounds that regulate keratinocytes and fibroblasts responses have significant and safe therapeutic effects. The demand for natural product-based ingredients in sunscreen formulations is rising. Natural compounds show promising anti-photoaging effects by targeting cellular pathways in keratinocytes and fibroblasts, providing potential therapeutic strategies. However, comprehensive clinical studies are needed to verify their efficacy and safety in mitigating photoaging, which should use advanced pharmacological methods to uncover the complex anti-photoaging mechanisms of natural compounds.

Boosting of retinol activity using novel lecithin: Retinol acyltransferase inhibitors.

Lecithin:retinol acyltransferase (LRAT) is the main enzyme catalysing the esterification of retinol to retinyl esters and, hence, is of central importance for retinol homeostasis. As retinol, by its metabolite retinoic acid, stimulates fibroblasts to synthesize collagen fibres and inhibits collagen-degrading enzymes, the inhibition of LRAT presents an intriguing strategy for anti-ageing ingredients by increasing the available retinol in the skin. Here, we synthesized several derivatives mimicking natural lecithin substrates as potential LRAT inhibitors. By exploring various chemical modifications of the core scaffold consisting of a central amino acid and an N-terminal acylsulfone, we explored 10 different compounds in a biochemical assay, resulting in two compounds with IC50 values of 21.1 and 32.7 μM (compounds 1 and 2), along with a simpler arginine derivative with comparative inhibitory potency. Supported by computational methods, we investigated their structure-activity relationship, resulting in the identification of several structural features associated with high inhibition of LRAT. Ultimately, we conducted an exvivo study with human skin, demonstrating an increase of collagen III associated with a reduction of the skin ageing process. In conclusion, the reported compounds offer a promising approach to boost retinol abundance in human skin and might present a new generation of anti-ageing ingredients for cosmetic application.

Redox homeostasis and pH monitoring: a step forward to personalized medicine and dermatology

Skin is continually subjected to various environmental stressors, such as pollution, UV rays, and other oxidative damage factors. It is obligatory to ascertain the exact importance of redox status and ROS indicators, which may be assessed in diverse physiological fluids and tissues. Reactive oxygen species (ROS) can cause lipid peroxidation, which can compromise the integrity and functionality of skin cells by degrading membrane lipids. This may compromise the skin barrier, making the skin more prone to infections and environmental irritants, increasing water loss and dryness. Collagen in the dermis can covalently link to malondialdehyde (MDA), a byproduct of lipid peroxidation generated by oxidatively damaged skin lipids, to form MDA-collagen adducts. Several types of skin cancer are associated with a heightened vulnerability of DNA purine and pyrimidine bases to oxidative damage and altered DNA repair capacity (DRC). Damage from ROS may cause hyaluronate to become less viscous, which increases its susceptibility to degradation. Elastin hydrodynamic radius decreased the rate of self-assembly in response to ROS. Alterations in redox homeostasis can lead to various diseases and conditions, including vitiligo, actinic keratosis, psoriasis, contact dermatitis, systemic sclerosis, the onset of wrinkles, and skin aging. The most recent formulations' capacity to improve pH and Redox simultaneously can be attained by carefully selecting proposed antioxidant formulations. The combination of modern preparations is currently available and should be used in accordance with the suggested guidelines.

The Effect of Combination Cream of Patchouli Extract and Arabica Gayo Coffee Peel Extract on Aging Skin

The Effect of Combination Cream of Patchouli Extract and Arabica Gayo Coffee Peel Extract on Aging Skin

Engineering a durable BDDE cross-linked collagen filler for skin rejuvenation

Skin aging, characterized by reduced regeneration, chronic inflammation, and heightened skin cancer risk, poses a significant challenge. Collagen fillers have emerged as a potential solution for skin rejuvenation by stimulating collagen regeneration. However, their clinical efficacy is limited by inherent instability and vulnerability toin vivodegradation by collagenase. Chemical cross-linking presents a promising approach to enhance stability, but it carries risks such as cytotoxicity, calcification, and discoloration. Here, we introduce a highly durable 1,4-butanediol diglycidyl ether (BDDE) cross-linked collagen filler for skin rejuvenation. BDDE effectively cross-links collagen, resulting in fillers with exceptional mechanical strength and injectability. These fillers demonstrate favorable stability and durability, promoting proliferation, adhesion, and spreading of human foreskin fibroblast-1 cellsin vitro. In vivostudies confirm enhanced collagen regeneration without inducing calcification. BDDE cross-linked collagen fillers offer promising prospects for medical cosmetology and tissue regeneration.

Skrining Kesehatan Kulit dengan Penilaian Kadar Air dan Minyak pada Kelompok Usia Produktif di Sekolah Kalam Kudus II, Duri Kosambi

Skin health, as the body's largest organ, is an important aspect of health. It plays an important role such as: protection against pathogens, regulating temperature, and preventing fluid loss. Internal factors such as genetics, hormones, and general health, as well as external factors such as UV exposure, pollution, skin care habits, and diet, influence skin health. The aim of this activity is to increase health awareness and provide education about the importance of maintaining healthy skin. Community service activities were done at Kalam Kudus II High School using the PDCA (Plan-Do-Check-Act) method. At the planning stage, skin health problems were identified and educational activity plans were drawn up. Implementation includes health seminars, individual consultation sessions, and skin examinations using a skin analyzer to assess the oil and water content of the skin. Evaluation was carried out by collecting feedback from participants, and follow-up actions were prepared based on the evaluation results. A total of 68 participants took part in this activity. It was observed that in 18-35 year age group, skin conditions were more stable compared to the 36-50 year age group. In which the latter was starting to show signs of skin aging. This also shown in the 51-64 year age group whom experiencing dry skin and other skin problems more often.

Skin Aging and the Upcoming Role of Ferroptosis in Geroscience.

The skin is considered the most important organ system in mammals, and as the population ages, it is important to consider skin aging and anti-aging therapeutic strategies. Exposure of the skin to various insults induces significant changes throughout our lives, differentiating the skin of a young adult from that of an older adult. These changes are caused by a combination of intrinsic and extrinsic aging. We report the interactions between skin aging and its metabolism, showing that the network is due to several factors. For example, iron is an important nutrient for humans, but its level increases with aging, inducing deleterious effects on cellular functions. Recently, it was discovered that ferroptosis, or iron-dependent cell death, is linked to aging and skin diseases. The pursuit of new molecular targets for ferroptosis has recently attracted attention. Prevention of ferroptosis is an effective therapeutic strategy for the treatment of diseases, especially in old age. However, the pathological and biological mechanisms underlying ferroptosis are still not fully understood, especially in skin diseases such as melanoma and autoimmune diseases. Only a few basic studies on regulated cell death exist, and the challenge is to turn the studies into clinical applications.

Poly-L-Lactic Acid Reduces the Volume of Dermal Adipose Tissue Through its Metabolite Lactate.

Poly-L-lactic acid (PLLA), a well-established biostimulator that induces collagenases, is widely used among clinical practice to treat skin aging. However, the precise regulatory effect of PLLA on different dermal cell subsets beyond fibroblast has not been fully elucidated. In this study, we constructed in vivo PLLA injection and in vitro PLLA-adipocyte co-culture models to analyze the regulatory effects of PLLA on the volume, differentiation, lipolysis, and thermogenic capacity of dermal adipocyte. We found that PLLA injection significantly reduced the thickness of dermal fat in mice. In co-culture assay, PLLA showed no effect on adipogenesis, but stimulated the lipolysis activity. Interestingly, PLLA also enhanced the differentiation of fat cells into beige fat cells, which possess higher thermogenic capacity. In mechanical study, we blocked adipocyte lactate uptake with a monocarboxylate transporter (MCT1/4) inhibitor and found that the regulatory effect of PLLA on dermal adipocyte relies on its metabolite lactate. In summary, our results suggest that PLLA has complex regulatory effects on the dermal cells, and its ability to improve skin aging is not fully attributed to stimulating collagen synthesis, but also partially involves adipocytes.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Apigenin and Phloretin Combination for Skin Aging and Hyperpigmentation Regulation

Apigenin and Phloretin Combination for Skin Aging and Hyperpigmentation Regulation

Para-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models.

Para-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after H2O2 and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms. Here we demonstrate that pHCA prevents oxidative stress-induced premature senescence of human primary keratinocytes in both 2D and 3D skin models, while improving clonogenicity in 2D. As aging is linked to inflammation, referred to as inflammaging, we analyzed the release of IL-6, IL-8, and PGE2, known to be associated with senescence. All of them were downregulated by pHCA in both normal and oxidative stress conditions. Mechanistically, DNA damage induced by oxidative stress is prevented by pHCA, while pHCA also exerts a positive effect on the mitochondrial and glycolytic functions under stress. Altogether, these results highlight the protective effects of pHCA against inflammaging, and importantly, help to elucidate its potential mechanisms of action.

Alterations of Matrisome Gene Expression in Naturally Aged and Photoaged Human Skin In Vivo.

The main component of human skin is a collagen-rich extracellular matrix (ECM), known as the matrisome. The matrisome is essential for maintaining the structural integrity and mechanical properties of the skin. Recently, we reported notable decreases in matrisome proteins in natural aging and photoaging human skin. This study aims to investigate the mRNA expression of the core matrisome proteins in human skin, comparing young versus aged and sun-protected versus sun-exposed skin by quantitative real-time PCR and immunostaining. Our findings reveal a notable decrease in core matrisome transcription in aged skin. The mRNA expression of the core matrisome, such as collagen 1A1 (COL1A1), decorin, and dermatopontin, is significantly reduced in aged skin compared to its young skin. Yet, the majority of collagen mRNA expression levels of aged sun-exposed skin are similar to those found in young sun-exposed skin. This discrepancy is primarily attributable to a substantial decrease in collagen transcription in young sun-exposed skin, suggesting early molecular changes in matrisome transcription due to sun exposure, which preceded the emergence of clinical signs of photoaging. These findings shed light on the mRNA transcript profile of major matrisome proteins and their alterations in naturally aged and photoaged human skin, offering valuable insights into skin matrisome biology.