Search

Additional file 12: Figure S10. Regulation of genes of TGF-beta signaling pathway during senescence induction in MRC-5 strains. Genes of the “TGF-beta signaling” pathway which are significantly up- (green) and down- (red) regulated (log2 fold change >1) during irradiation induced senescence (120 h after 20 Gy irradiation) in MRC-5 fibroblast strains. Blue color signifies genes which are commonly down-regulated during both, irradiation induced and replicative senescence.

Growth curve and percentage of SA β-Gal positive cells in WI-38 fibroblasts +/− rotenone treatment. (A) Growth curve of WI-38 fibroblasts supplemented with 0.1 μM rotenone (green), compared to DMSO-treated controls (black). (B) Percentage of SA β-Gal positive cells in 0.1 μM rotenone-treated WI-38 fibroblasts (green), compared to DMSO-treated controls (black). The bars indicate the mean ± S.D. n = 3. (DOCX 26 kb)

Up-regulated pathways in human foreskin fibroblasts on low dose rotenone treatment. Pathways significantly (p

Down-regulated pathways in human foreskin fibroblasts on low dose rotenone treatment. Pathways significantly (p

The most significant commonly up- and down-regulated genes in primary human fibroblast strains independent of their cell origin. The common genes most significantly differentially regulated at transcript levels in low dose rotenone treated MRC-5 (PDs 42, 48) and HFFs (PDs 26, 30, 34) compared to untreated controls. These genes were selected according to the statistical stringency criteria of p

Common significantly up- and down-regulated pathways in primary human fibroblast strains independent of their cell origin. Pathways significantly (p

Apoptosis induction by higher concentrations of rotenone treatment in MRC-5 fibroblasts. Numbers of days MRC-5 fibroblasts were maintained in culture before induction of apoptosis (as detected by phosphorylation of p38) in response to different concentrations of rotenone. (DOCX 15 kb)

Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing based on gene expression data from four vertebrate species across four tissues. We find that ageing-associated transcriptomic changes follow trajectories similar to the transcriptional alterations observed in degenerative ageing diseases but are in opposite direction to the transcriptomic alterations observed in cancer. We confirm the existence of a similar antagonism on the genomic level, where a majority of shared risk alleles which increase the risk of cancer decrease the risk of chronic degenerative disorders and vice versa. These results reveal a fundamental trade-off between cancer and degenerative ageing diseases that sheds light on the pronounced shift in their epidemiology during ageing., Nature Communications, 9, ISSN:2041-1723

Summary The killifish Nothobranchius furzeri is the shortest-lived vertebrate that can be bred in the laboratory. Its rapid growth, early sexual maturation, fast aging, and arrested embryonic development (diapause) make it an attractive model organism in biomedical research. Here, we report a draft sequence of its genome that allowed us to uncover an intra-species Y chromosome polymorphism representing—in real time—different stages of sex chromosome formation that display features of early mammalian XY evolution "in action." Our data suggest that gdf6Y , encoding a TGF-β family growth factor, is the master sex-determining gene in N. furzeri . Moreover, we observed genomic clustering of aging-related genes, identified genes under positive selection, and revealed significant similarities of gene expression profiles between diapause and aging, particularly for genes controlling cell cycle and translation. The annotated genome sequence is provided as an online resource (http://www.nothobranchius.info/NFINgb).

Replicative senescence is of fundamental importance for the process of cellular aging, since it is a property of most of our somatic cells. Here, we elucidated this process by comparing gene expression changes, measured by RNA-seq, in fibroblasts originating from two different tissues, embryonic lung (MRC-5) and foreskin (HFF), at five different time points during their transition into senescence. Although the expression patterns of both fibroblast cell lines can be clearly distinguished, the similar differential expression of an ensemble of genes was found to correlate well with their transition into senescence, with only a minority of genes being cell line specific. Clustering-based approaches further revealed common signatures between the cell lines. Investigation of the mRNA expression levels at various time points during the lifespan of either of the fibroblasts resulted in a number of monotonically up- and downregulated genes which clearly showed a novel strong link to aging and senescence related processes which might be functional. In terms of expression profiles of differentially expressed genes with age, common genes identified here have the potential to rule the transition into senescence of embryonic lung and foreskin fibroblasts irrespective of their different cellular origin.