MOLECULAR MECHANISMS OF RETARDATION OF SKIN AGING UNDER INFLUENCE 0F HUMAN PLACENTA HYDROLYSATE

As the most voluminous organ of the body that is exposed to the outer environment, the skin suffers from both intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, laxity, and rough-textured appearance. This aging process is accompanied with phenotypic changes in cutaneous cells as well as structural and functional changes in extracellular matrix components such as collagens and elastin. In this review, we summarize these changes in skin aging, research advances of the molecular mechanisms leading to these changes, and the treatment strategies aimed at preventing or reversing skin aging.

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Quercetin Directly Targets JAK2 and PKCδ and Prevents UV-Induced Photoaging in Human Skin

International Journal of Molecular Sciences ◽

10.3390/ijms20215262 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5262 ◽

Cited By ~ 7

Author(s):

Shin ◽

Lee ◽

Hong ◽

Lim ◽

Byun

Keyword(s):

Protein Kinase ◽

Human Skin ◽

Fruits And Vegetables ◽

Molecular Mechanisms ◽

Skin Aging ◽

Janus Kinase ◽

Activator Protein 1 ◽

Protective Effects ◽

Matrix Metalloproteinase 1 ◽

Extracellular Signal

Quercetin is a naturally occurring polyphenol present in various fruits and vegetables. The bioactive properties of quercetin include anti-oxidative, anti-cancer, anti-inflammatory, and anti-diabetic effects. However, the effect of quercetin on skin aging and the direct molecular targets responsible have remained largely unknown. Herein, we investigated the protective effect of quercetin against UV-mediated skin aging and the molecular mechanisms responsible. Treatment with quercetin suppressed UV-induced matrix metalloproteinase-1 (MMP-1) and cyclooxygenase-2 (COX-2) expression and prevented UV-mediated collagen degradation in human skin tissues. Quercetin exerted potent inhibitory effects towards UV-induced activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) activity. Further examination of the upstream signaling pathways revealed that quercetin can attenuate UV-mediated phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N terminal kinases (JNK), protein kinase B (Akt), and signal transducer and activator of transcription 3 (STAT3). Kinase assays using purified protein demonstrated that quercetin can directly inhibit protein kinase C delta (PKCδ) and Janus kinase 2 (JAK2) kinase activity. Quercetin was observed to bind to PKCδ and JAK2 in pull-down assays. These findings suggest that quercetin can directly target PKCδ and JAK2 in the skin to elicit protective effects against UV-mediated skin aging and inflammation. Our results highlight the potential use of quercetin as a natural agent for anti-skin aging applications.

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Montagna Symposium 2014—Skin Aging: Molecular Mechanisms and Tissue Consequences

Journal of Investigative Dermatology ◽

10.1038/jid.2014.546 ◽

2015 ◽

Vol 135 (4) ◽

pp. 950-953 ◽

Cited By ~ 8

Author(s):

Barbara A. Gilchrest ◽

Judith Campisi ◽

Howard Y. Chang ◽

Gary J. Fisher ◽

Molly F. Kulesz-Martin

Keyword(s):

Molecular Mechanisms ◽

Skin Aging

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Integrating High-Throughput Approaches and in vitro Human Trophoblast Models to Decipher Mechanisms Underlying Early Human Placenta Development

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.673065 ◽

2021 ◽

Vol 9 ◽

Author(s):

Bum-Kyu Lee ◽

Jonghwan Kim

Keyword(s):

High Throughput ◽

Human Placenta ◽

Molecular Mechanisms ◽

Molecular Level ◽

Cell Types ◽

Model Systems ◽

Extravillous Trophoblast ◽

Human Trophoblast ◽

Early Human

The placenta is a temporary but pivotal organ for human pregnancy. It consists of multiple specialized trophoblast cell types originating from the trophectoderm of the blastocyst stage of the embryo. While impaired trophoblast differentiation results in pregnancy disorders affecting both mother and fetus, the molecular mechanisms underlying early human placenta development have been poorly understood, partially due to the limited access to developing human placentas and the lack of suitable human in vitro trophoblast models. Recent success in establishing human trophoblast stem cells and other human in vitro trophoblast models with their differentiation protocols into more specialized cell types, such as syncytiotrophoblast and extravillous trophoblast, has provided a tremendous opportunity to understand early human placenta development. Unfortunately, while high-throughput research methods and omics tools have addressed numerous molecular-level questions in various research fields, these tools have not been widely applied to the above-mentioned human trophoblast models. This review aims to provide an overview of various omics approaches that can be utilized in the study of human in vitro placenta models by exemplifying some important lessons obtained from omics studies of mouse model systems and introducing recently available human in vitro trophoblast model systems. We also highlight some key unknown questions that might be addressed by such techniques. Integrating high-throughput omics approaches and human in vitro model systems will facilitate our understanding of molecular-level regulatory mechanisms underlying early human placenta development as well as placenta-associated complications.

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Enhancing Skin Health: By Oral Administration of Natural Compounds and Minerals with Implications to the Dermal Microbiome

International Journal of Molecular Sciences ◽

10.3390/ijms19103059 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3059 ◽

Cited By ~ 13

Author(s):

David Vollmer ◽

Virginia West ◽

Edwin Lephart

Keyword(s):

Molecular Mechanisms ◽

Scientific Journal ◽

Topical Administration ◽

Skin Aging ◽

Skin Microbiome ◽

Therapeutic Benefits ◽

Oral Consumption ◽

Medicinal Treatment ◽

History Of ◽

Year 2000

The history of cosmetics goes back to early Egyptian times for hygiene and health benefits while the history of topical applications that provide a medicinal treatment to combat dermal aging is relatively new. For example, the term cosmeceutical was first coined by Albert Kligman in 1984 to describe topical products that afford both cosmetic and therapeutic benefits. However, beauty comes from the inside. Therefore, for some time scientists have considered how nutrition reflects healthy skin and the aging process. The more recent link between nutrition and skin aging began in earnest around the year 2000 with the demonstrated increase in peer-reviewed scientific journal reports on this topic that included biochemical and molecular mechanisms of action. Thus, the application of: (a) topical administration from outside into the skin and (b) inside by oral consumption of nutritionals to the outer skin layers is now common place and many journal reports exhibit significant improvement for both on a variety of dermal parameters. Therefore, this review covers, where applicable, the history, chemical structure, and sources such as biological and biomedical properties in the skin along with animal and clinical data on the oral applications of: (a) collagen, (b) ceramide, (c) β-carotene, (d) astaxanthin, (e) coenzyme Q10, (f) colostrum, (g) zinc, and (h) selenium in their mode of action or function in improving dermal health by various quantified endpoints. Lastly, the importance of the human skin microbiome is briefly discussed in reference to the genomics, measurement, and factors influencing its expression and how it may alter the immune system, various dermal disorders, and potentially be involved in chemoprevention.

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Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms

Ageing Research Reviews ◽

10.1016/j.arr.2016.08.001 ◽

2016 ◽

Vol 31 ◽

pp. 36-54 ◽

Cited By ~ 81

Author(s):

Edwin D. Lephart

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Skin Aging ◽

Aging Effects ◽

And Oxidative Stress

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CD98hc (SLC3A2) regulation of skin homeostasis wanes with age

Journal of Experimental Medicine ◽

10.1084/jem.20121651 ◽

2013 ◽

Vol 210 (1) ◽

pp. 173-190 ◽

Cited By ~ 21

Author(s):

Etienne Boulter ◽

Soline Estrach ◽

Aurélia Errante ◽

Catherine Pons ◽

Laurence Cailleteau ◽

...

Keyword(s):

Cell Adhesion ◽

Amino Acid ◽

Molecular Mechanisms ◽

Skin Aging ◽

Amino Acid Transporters ◽

Appreciable Effect ◽

Nucleotide Exchange ◽

Aged Skin

Skin aging is linked to reduced epidermal proliferation and general extracellular matrix atrophy. This involves factors such as the cell adhesion receptors integrins and amino acid transporters. CD98hc (SLC3A2), a heterodimeric amino acid transporter, modulates integrin signaling in vitro. We unravel CD98hc functions in vivo in skin. We report that CD98hc invalidation has no appreciable effect on cell adhesion, clearly showing that CD98hc disruption phenocopies neither CD98hc knockdown in cultured keratinocytes nor epidermal β1 integrin loss in vivo. Instead, we show that CD98hc deletion in murine epidermis results in improper skin homeostasis and epidermal wound healing. These defects resemble aged skin alterations and correlate with reduction of CD98hc expression observed in elderly mice. We also demonstrate that CD98hc absence in vivo induces defects as early as integrin-dependent Src activation. We decipher the molecular mechanisms involved in vivo by revealing a crucial role of the CD98hc/integrins/Rho guanine nucleotide exchange factor (GEF) leukemia-associated RhoGEF (LARG)/RhoA pathway in skin homeostasis. Finally, we demonstrate that the deregulation of RhoA activation in the absence of CD98hc is also a result of impaired CD98hc-dependent amino acid transports.

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Charting host-microbe co-metabolism in skin aging and application to metagenomics data

PLoS ONE ◽

10.1371/journal.pone.0258960 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0258960

Author(s):

Wynand Alkema ◽

Jos Boekhorst ◽

Robyn T. Eijlander ◽

Steve Schnittger ◽

Fini De Gruyter ◽

...

Keyword(s):

Human Skin ◽

Molecular Mechanisms ◽

Markov Models ◽

Age Groups ◽

Skin Aging ◽

Protein Glycation ◽

Rrna Gene ◽

Skin Microbiome ◽

Sequencing Data ◽

Extrinsic Factors

During aging of human skin, a number of intrinsic and extrinsic factors cause the alteration of the skin’s structure, function and cutaneous physiology. Many studies have investigated the influence of the skin microbiome on these alterations, but the molecular mechanisms that dictate the interplay between these factors and the skin microbiome are still not fully understood. To obtain more insight into the connection between the skin microbiome and the human physiological processes involved in skin aging, we performed a systematic study on interconnected pathways of human and bacterial metabolic processes that are known to play a role in skin aging. The bacterial genes in these pathways were subsequently used to create Hidden Markov Models (HMMs), which were applied to screen for presence of defined functionalities in both genomic and metagenomic datasets of skin-associated bacteria. These models were further applied on 16S rRNA gene sequencing data from skin microbiota samples derived from female volunteers of two different age groups (25–28 years (‘young’) and 59–68 years (‘old’)). The results show that the main bacterial pathways associated with aging skin are those involved in the production of pigmentation intermediates, fatty acids and ceramides. This study furthermore provides evidence for a relation between skin aging and bacterial enzymes involved in protein glycation. Taken together, the results and insights described in this paper provide new leads for intervening with bacterial processes that are associated with aging of human skin.

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