Distribution of the slope parameter <i>b</i> of simulated distributions by different simulation settings.

<p>sim. = simulations, repl. = replicates.</p

Comparison of , and .

<p>Comparison of , and .</p

Five empirical evaluations of the −log₁₀(<i>P</i>)-distribution of the statistic, each obtained by simulating 2 × 10⁹ replicates.

<p>The theoretical distribution was obtained by fitting a straight line. The grey shaded area reflects the 95% Clopper-Pearson confidence interval [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154872#pone.0154872.ref007" target="_blank">7</a>].</p

Metabolomics profiling reveals novel markers for leukocyte telomere length

Leukocyte telomere length (LTL) is considered one of the most predictive markers of biological aging. The aim of this study was to identify novel pathways regulating LTL using a metabolomics approach. To this end, we tested associations between 280 blood metabolites and LTL in 3511 females from TwinsUK and replicated our results in the KORA cohort. We furthermore tested significant metabolites for associations with several aging-related phenotypes, gene expression markers and epigenetic markers to investigate potential underlying pathways. Five metabolites were associated with LTL: Two lysolipids, 1-stearoylglycerophosphoinositol (P=1.6×10-5) and 1-palmitoylglycerophosphoinositol (P=1.6×10-5), were found to be negatively associated with LTL and positively associated with phospholipase A2 expression levels suggesting an involvement of fatty acid metabolism and particularly membrane composition in biological aging. Moreover, two gamma-glutamylamino acids, gamma-glutamyltyrosine (P=2.5×10-6) and gamma-glutamylphenylalanine (P=1.7×10-5), were negatively correlated with LTL. Both are products of the glutathione cycle and markers for increased oxidative stress. Metabolites were also correlated with functional measures of aging, i.e. higher blood pressure and HDL cholesterol levels and poorer lung, liver and kidney function. Our results suggest an involvement of altered fatty acid metabolism and increased oxidative stress in human biological aging, reflected by LTL and age-related phenotypes of vital organ systems

<i>TGM1</i>, <i>TGM3</i> and <i>TGM5</i> gene expression in the skin of AD patients and healthy controls.

<p>TGM transcript levels (A, E and I) of healthy controls (HC, n = 10) non lesional skin of AD patients (NL, n = 7) and lesional skin from AD patients (L, n = 10). Horizontal bars represent median values in each group and data is presented on a logaritmic scale. For IHC analysis of the TG protein expression, skin sections from nine AD patients and ten healthy controls were stained. Representative staining from one healthy control and one patient is shown in the figure for TG1 (B–D), TG3 (F–H) and TG5 (J–L) expression. Scale bar represents 50 µm.</p