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. 2015 Oct 19:5:15145.
doi: 10.1038/srep15145.

Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

Jialiang Yang  1   2 , Tao Huang  1   2 , Francesca Petralia  1   2 , Quan Long  1   2 , Bin Zhang  1   2 , Carmen Argmann  1   2 , Yong Zhao  1   2 , Charles V Mobbs  3   4   5 , Eric E Schadt  1   2 , Jun Zhu  1   2 , Zhidong Tu  1   2 ; GTEx Consortium
Collaborators, Affiliations

Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

Jialiang Yang et al. Sci Rep. .

Erratum in

Abstract

Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger "co-aging" than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Age distribution of donors in nine tissues.
The histograms of donor age distribution for all samples, females only, and males only.
Figure 2
Figure 2. Age-associated gene expression in subcutaneous adipose tissue.
(a) Heatmap of 1,134 age-associated genes (row) on 94 samples (column). Colors represent normalized gene expression values with blue for low expression and red for high expression. The age of each individual is displayed at the bottom and also illustrated in color bar at the top with dark green for young and yellow for old. (b) Scatter plot of 2 representative age-associated gene expression patterns PYH1N1 and EIF5AL1 in adipose tissue. Pearson-R value in the title represents the Pearson correlation coefficient between gene expression and age across all samples. The solid blue triangles plot male samples and solid red circle female samples. Similarly, the blue and red lines denote the regression lines for male and female samples, respectively.
Figure 3
Figure 3. Aging synchronization in multiple tissues.
(a) Heatmap of tissue co-aging in adipose, artery, heat, lung, muscle, nerve, and blood tissues. The number in each square in the lower triangle indicates the co-aging coefficient between a tissue pair; and the sample number for each tissue is also presented in the top of the sample column. (b) Scatter plot of age rank correlation for two highly correlated tissues lung and blood and the regression line. Spearman-R value represents the Spearman correlation coefficient between the ranks defined by the two tissues across all samples. (c) Scatter plot of age rank correlation for two relatively uncorrelated tissues muscle and blood and the regression line. (d) Scatter plot of age rank correlation for heart, lung, and blood; the axis ranges from 0 to 60 indicating the rank of each sample (in total 59 donors with data in all these 3 tissues); the chronological ages are marked for some representative samples and the outliers are highlighted in red. (e) Correlation between age rank deviation and age in artery and nerve. The shaded area indicates the confidence interval of the regression line. “p-value” indicates the p-value for regression coefficient being deviated from 0. (f) Correlation between rank deviation and age in lung and blood.
Figure 4
Figure 4. Correlation between age and common diseases in multiple tissues.
(a) Overlap enrichment between up-regulated aging genes and disease genes in GTEx tissues and (b) Overlap enrichment between down-regulated aging genes and disease genes in GTEx tissues. The color depth indicates the normalized negative logarithm of the p-value of the Fisher’s exact test for overlapping between disease and aging genes in specific tissue.
See this image and copyright information in PMC

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