MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain
- Mehmet Somel1,2,7,8,
- Song Guo1,7,
- Ning Fu3,7,
- Zheng Yan1,
- Hai Yang Hu1,
- Ying Xu1,
- Yuan Yuan1,4,
- Zhibin Ning3,
- Yuhui Hu5,
- Corinna Menzel6,
- Hao Hu6,
- Michael Lachmann2,
- Rong Zeng3,
- Wei Chen5,6,8 and
- Philipp Khaitovich1,2,8
- 1 Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
- 2 Max Planck Institute for Evolutionary Anthropology, Leipzig 04103, Germany;
- 3 Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;
- 4 Faculty of Science, Technology and Engineering, La Trobe University, Melbourne, VIC 3086, Australia;
- 5 Max Delbrück Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Berlin-Buch 13092, Germany;
- 6 Max Planck Institute for Molecular Genetics, Berlin 14195, Germany
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↵7 These authors contributed equally to this work.
Abstract
Changes in gene expression levels determine differentiation of tissues involved in development and are associated with functional decline in aging. Although development is tightly regulated, the transition between development and aging, as well as regulation of post-developmental changes, are not well understood. Here, we measured messenger RNA (mRNA), microRNA (miRNA), and protein expression in the prefrontal cortex of humans and rhesus macaques over the species' life spans. We find that few gene expression changes are unique to aging. Instead, the vast majority of miRNA and gene expression changes that occur in aging represent reversals or extensions of developmental patterns. Surprisingly, many gene expression changes previously attributed to aging, such as down-regulation of neural genes, initiate in early childhood. Our results indicate that miRNA and transcription factors regulate not only developmental but also post-developmental expression changes, with a number of regulatory processes continuing throughout the entire life span. Differential evolutionary conservation of the corresponding genomic regions implies that these regulatory processes, although beneficial in development, might be detrimental in aging. These results suggest a direct link between developmental regulation and expression changes taking place in aging.
Footnotes
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↵8 Corresponding authors.
E-mail somel{at}eva.mpg.de.
E-mail wei.chen{at}mdc-berlin.de.
E-mail khaitovich{at}eva.mpg.de.
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[Supplemental material is available online at http://www.genome.org. All mRNA, miRNA, and protein expression data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under series accession no. GSE18069.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.106849.110.
- Received February 22, 2010.
- Accepted June 9, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.