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Transcriptional Profile of Aging in Healthy Human Skin

ABSTRACT: Gene expression changes were assessed from the non sun-exposed skin of the lower back of 98 healthy males aged 19-86. We show that contrary to previous thought, genome wide transcriptional activity does not display an exclusively linear correlation with ageing, but rather, in human skin, undergoes a period of significant transient change between 30 and 45 years of age. The identified transient transcriptional changes suggest a period of heightened metabolic activity and cellular damage mediated primarily through the actions of TP53 (tumour protein 53) and TNF (tumour necrosis factor). We also identified a subgroup of the population characterised by increased expression of a large group of hair follicle genes that correlates strongly with a younger age of onset and increasing severity of androgenetic alopecia. Skin was collected from the lower back at the level of the belt, aproximately 5cm lateral to midline from healthy males, (defined as; non-smoking, no hospital admissions in the previous 5 years, no significant medical conditions or medications). Each sample was individually hybridised to an exon 1.0 ST array.

ORGANISM(S): Homo sapiens

SUBMITTER: Daniel Haustead

PROVIDER: E-GEOD-18876 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptional Profile of Aging in Healthy Human Skin

Project description:Gene expression changes were assessed from the non sun-exposed skin of the lower back of 98 healthy males aged 19-86. We show that contrary to previous thought, genome wide transcriptional activity does not display an exclusively linear correlation with ageing, but rather, in human skin, undergoes a period of significant transient change between 30 and 45 years of age. The identified transient transcriptional changes suggest a period of heightened metabolic activity and cellular damage mediated primarily through the actions of TP53 (tumour protein 53) and TNF (tumour necrosis factor). We also identified a subgroup of the population characterised by increased expression of a large group of hair follicle genes that correlates strongly with a younger age of onset and increasing severity of androgenetic alopecia.

2011-11-01 | GSE18876 | GEO

Gene expression patterns induced by a transient switch-on of ROS production in mouse skin

Project description:Gene expression signatures induced by transient ROS production were characterized in both mouse back skin and tail epidermis samples. A transient in situ ROS production in the tissue was activated by an adapted photodynamic treatment, using methyl aminolevulinate as a metabolic precursor of endogenous Protoporphyrin IX. Gene expression in skin samples was measured 48 h after the photodynamic treatment. Experimental groups included: [1] Back skin control group (n=3 animals); [2] Back skin treated group (n=3 animals); [3] Tail skin control group (n=3 animals); and [4] Tail skin treated group (n=3 animals).

2014-02-25 | E-GEOD-55135 | biostudies-arrayexpress

Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (carcinomas)

Project description:Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence. Skin tumors were induced on dorsal back skin from a Mus spretus / Mus musculus backcross ([SPRET/Ei X FVB/N] X FVB/N) mice by treatment of dorsal back skin with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). This treatment induced multiple benign papillomas as well as malignant squamous cell carcinomas (SCC) and spindle cell carcinomas. 60 carcinomas were harvested from 55 mice; five mice provided two carcinomas each.

2010-12-22 | E-GEOD-21247 | biostudies-arrayexpress

Gene expression patterns induced by a transient switch-on of ROS production in mouse skin

2014-02-25 | GSE55135 | GEO

Network Analysis of Skin Tumor Progression Identifies a Rewired Genetic Architecture Affecting Inflammation and Tumor Susceptibility (papillomas)

Project description:Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence. Skin tumors were induced on dorsal back skin from a Mus spretus / Mus musculus backcross ([SPRET/Ei X FVB/N] X FVB/N) mice by treatment of dorsal back skin with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). This treatment induced multiple benign papillomas as well as malignant squamous cell carcinomas (SCC) and spindle cell carcinomas. Gene expression analysis was performed on mRNA extracted from 68 papillomas: two papillomas from each of 31 FVBBX mice and a single papilloma from six additional FVBBX mice. Papillomas were harvested when mice were sacrificed due to presence of a carcinoma or termination of the experiment.

2010-12-22 | E-GEOD-21263 | biostudies-arrayexpress

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Project description:Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor NRL. The loss of Nrl in mice (Nrl-/-) results in a retina with predominantly S-opsin containing cones that exhibit molecular and functional characteristics of WT cones. Here we report that Nrl-/- retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by four months of age, resulting in a thinned but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic ERG. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of stress response and inflammation genes, implying their involvement in cone death. The Nrl-/- retina illustrates the long-term viability of cones in the absence of rods and may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula. Targets were generated from a pair of retinas (one Nrl-/- mouse) per biological replicate. Four biological replicates were generated for each of the five aging timepoints (1, 2, 4, 6, and 10 months post natal).

2011-11-15 | E-GEOD-33674 | biostudies-arrayexpress

PTHR1 knock-down in osteosarcoma cells

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2021-11-14 | GSE122598 | GEO

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