Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases
Authors: Yang Jialiang , Huang Tao , Petralia Francesca , Long Quan , Zhang Bin , Argmann Carmen , Zhao Yong , Mobbs Charles V. , Schadt Eric E. , Zhu Jun , Tu Zhidong ,   The GTEx Consortium, Ardlie Kristin G. , Deluca David S. , Segrè Ayellet V. , Sullivan Timothy J. , Young Taylor R. , Gelfand Ellen T. , Trowbridge Casandra A. , Maller Julian B. , Tukiainen Taru , Lek Monkol , Ward Lucas D. , Kheradpour Pouya , Iriarte Benjamin , Meng Yan , Palmer Cameron D. , Winckler Wendy , Hirschhorn Joel , Kellis Manolis , MacArthur Daniel G. , Getz Gad , Shablin Andrey A. , Li Gen , Zhou Yi-Hui , Nobel Andrew B. , Rusyn Ivan , Wright Fred A. , Lappalainen Tuuli , Ferreira Pedro G. , Ongen Halit , Rivas Manuel A. , Battle Alexis , Mostafavi Sara , Monlong Jean , Sammeth Michael , Mele Marta , Reverter Ferran , Goldmann Jakob , Koller Daphne , Guigo Roderic , McCarthy Mark I. , Dermitzakis Emmanouil T. , Gamazon Eric R. , Konkashbaev Anuar , Nicolae Dan L. , Cox Nancy J. , Flutre Timothée , Wen Xiaoquan , Stephens Matthew , Pritchard Jonathan K. , Lin Luan , Liu Jun , Brown Amanda , Mestichelli Bernadette , Tidwell Denee , Lo Edmund , Salvatore Mike , Shad Saboor , Thomas Jeffrey A. , Lonsdale John T. , Choi Christopher , Karasik Ellen , Ramsey Kimberly , Moser Michael T. , Foster Barbara A. , Gillard Bryan M. , Syron John , Fleming Johnelle , Magazine Harold , Hasz Rick , Walters Gary D. , Bridge Jason P. , Miklos Mark , Sullivan Susan , Barker Laura K. , Traino Heather , Mosavel Magboeba , Siminoff Laura A. , Valley Dana R. , Rohrer Daniel C. , Jewel Scott , Branton Philip , Sobin Leslie H. , Qi Liqun , Hariharan Pushpa , Wu Shenpei , Tabor David , Shive Charles , Smith Anna M. , Buia Stephen A. , Undale Anita H. , Robinson Karna L. , Roche Nancy , Valentino Kimberly M. , Britton Angela , Burges Robin , Bradbury Debra , Hambright Kenneth W. , Seleski John , Korzeniewski Greg E. , Erickson Kenyon , Marcus Yvonne , Tejada Jorge , Taherian Mehran , Lu Chunrong , Robles Barnaby E. , Basile Margaret , Mash Deborah C. , Volpi Simona , Struewing Jeff , Temple Gary F. , Boyer Joy , Colantuoni Deborah , Little Roger , Koester Susan , Carithers NCI Latarsha J. , Moore Helen M. , Guan Ping , Compton Carolyn , Sawyer Sherilyn J. , Demchok Joanne P. , Vaught Jimmie B. , Rabiner Chana A. , Lockhart Nicole C. 
Published: October 2015

AbstractAging 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.