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

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

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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.

Original languageEnglish (US)
Article number15145
JournalScientific reports
Volume5
DOIs
StatePublished - Oct 19 2015

ASJC Scopus subject areas

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    Yang, J., Huang, T., Petralia, F., Long, Q., Zhang, B., Argmann, C., Zhao, Y., Mobbs, C. V., Schadt, E. E., Zhu, J., Tu, Z., Ardlie, K. G., Deluca, D. S., Segrè, A. V., Sullivan, T. J., Young, T. R., Gelfand, E. T., Trowbridge, C. A., Maller, J. B., ... Lockhart, N. C. (2015). Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases. Scientific reports, 5, [15145]. https://doi.org/10.1038/srep15145