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

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.JY is supported through Berg postdoc fellowship. ZT receives financial support from Berg Pharma as a consultant. ZT JZ ES receive support from Fondation Leducq Understanding coronary artery disease genes grant. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI/SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by supplements to University of Miami grants DA006227 & DA033684 and to contract N01MH000028. Statistical Methods development grants were made to the University of Geneva (MH090941 & MH101814), the University of Chicago (MH090951, MH090937, MH101820, MH101825), the University of North Carolina - Chapel Hill (MH090936 & MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St Louis (MH101810), and the University of Pennsylvania (MH101822)

DESA1002 'Continuous City' <Danielle Gardner>

My familiarity of the design process has been extended and I have found this semester to be a rewarding and worthwhile experience where I have been challenged and have begun to have a clearer understanding of the different approaches and techniques used in design and architecture. The exercises have been valuable with ongoing weekly research benefiting us with our independence in following up queries on our own and improving our critical thinking. The experience of presenting in front of a group of people in the design classes is an area that I needed to improve on and something that I have appreciated. At times I have found myself to be nervous and uncomfortable about having to express my opinions although doing this repetitively has enhanced my capabilities and given me confidence. I have enjoyed the experience of seeing a project through from the beginning, starting with the selection of an appropriate site and balancing up the options of orientation, site size, accessibility in order to come to an appropriate resolution. As I have progressed through I have changed my design in accordance with feedback and formed new ideas and concepts that eventuated through this design process