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Homo sapiens

ABSTRACT: Molecular Rejuvenation of Gene Expression Pattern of Photoaged and Intrinsically Aged Human Skin by Broadband Light Treatment

PROVIDER: PRJNA170133 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR519065.fastq.gz	Fastqsanger.gz
	SRR519066.fastq.gz	Fastqsanger.gz
	SRR519067.fastq.gz	Fastqsanger.gz
	SRR519068.fastq.gz	Fastqsanger.gz
	SRR519069.fastq.gz	Fastqsanger.gz

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Molecular Rejuvenation of Gene Expression Pattern of Photoaged and Intrinsically Aged Human Skin by Broadband Light Treatment

Project description:Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply deep sequencing of RNA 3' ends ("3-seq") to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed "skin aging") and the impact of broadband light (BBL) treatment. We find that skin aging was associated with the significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became "rejuvenated" after BBL treatment, i.e. more similar in expression level of youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long non-coding RNAs. Skin aging is not associated with systematic changes in 3' end mRNA processing. Hence, BBL treatment can restore the gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveals a novel set of targets that may lead to new insights into the human skin aging process. Examination of broadband light treated and untreated human skin transcriptomes of 5 women aged 50 years or more. They were compared to the skin transcriptomes of 5 young women aged 30 years or less.

2012-07-30 | E-GEOD-39170 | biostudies-arrayexpress

Molecular Rejuvenation of Gene Expression Pattern of Photoaged and Intrinsically Aged Human Skin by Broadband Light Treatment

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Novel skin photoageing biomarkers of epidermis and dermis revealed by traditional relative quantification in combination with a novel peptide locational fingerprinting MPLF.

Project description:Human skin undergoes profound structural remodelling following chronic exposure to ultraviolet radiation (UVR) – photoageing - that is normally studied by comparing photoexposed and photoprotected skin sites. Whilst it is well established that the abundance and distribution of major dermal extracellular matrix (ECM) proteins (principally collagen I and elastin) are compromised in skin, the influence of UVR exposure on other skin protein constituents, including epidermal proteins, is poorly understood. We used label-free LC-MS/MS proteomics to characterise the proteomic profiles of intrinsically aged buttock and photoaged forearm epidermis and dermis. Besides traditional shotgun proteomics we have also developed and used novel proteomics analysis approach to reveal locational changes in peptide yields from proteins named Manchester Peptide Locational Fingerprinting (MPLF) which is based on spectral counting. MPLF is a new proteomic analysis tool that can identify structural modification-associated differences within proteins from label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) datasets generated from biological samples. We have identified a total of 174 dermal proteins and 146 epidermal proteins with MPLF while relative quantification revealed a total of 635 dermal proteins and 926 epidermal proteins significantly different between photoaged forearm and intrinsically-aged buttock according to peak area intensity.

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Downregulation of miR-15b is associated with increased SIRT4 expression in premature senescence and photoaging of the skin

Project description:Sirtuins are deacetylases or ADP-ribosyltransferases which are implicated in multiple pathways involved in metabolism and life-span regulation. Here, we link the mitochondrial sirtuin SIRT4, which overexpression negatively impacts on mitochondrial oxidative capacity, with premature senescence and skin aging. Accordingly, SIRT4 mRNA levels were significantly increased in vitro in human dermal fibroblasts after repetitive UVB exposure or in senescence triggered by mitotic spindle stress or ionizing radiation. Similarly, analysis of SIRT4 expression in vivo in human skin revealed upregulation of SIRT4 mRNA levels in the dermal compartment of photaged skin as compared with the dermis of intrinsically aged skin. In all our in vitro models, upregulation of SIRT4 expression was associated with decreased levels of miR-15b. Also, in human skin, highest copy numbers of miR-15b mRNA were detected in the epidermis, and epidermal expression was significantly reduced in photoaged skin as compared with intrinsically aged skin. Reduced miR-15b expression is most likely causally linked to increased SIRT4 expression because we found that (i) miR-15b displays a conserved and direct binding site within the 3'-untranslated region of the SIRT4 gene as demonstrated by luciferase reporter assays and (ii) transfection of oligonucleotides mimicking miR-15b function was sufficient to prevent SIRT4 upregulation in senescent cells in vitro. Thus, we propose that miR-15b acts as a negative regulator of SIRT4 expression to antagonize mitochondrial dysfunction and hence cellular senescence as well as tissue aging, in particular photoaging of the skin.

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Project description:Proliferative and replicative senescent fibroblasts from aged human donors were reprogrammed towards pluripotency and re-differentiated in fibroblasts and then further analyzed for rejuvenation assessment. Comparison of microarrays were performed by non hierarchical clustering visualized in with Treeview software

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Transcriptomic Analysis of Wound Healing and Skin Rejuvenation Following Ablative Fractional Laser Treatment of Human Skin

Project description:Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment.

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