Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics

Rowland, Joshua, Akbarov, Artur, Eales, James, Xu, Xiaoguang, Dormer, John P., Guo, Hui, Denniff, Matthew, Jiang, Xiao, Ranjzad, Parisa, Nazgiewicz, Alicja, Ribeiro Prestes, Prescilla, Antczak, Andrzej, Szulinska, Monika, Wise, Ingrid A., Zukowska-Szczechowska, Ewa, Bogdanski, Pawel, Woolf, Adrian S., Samani, Nilesh J., Charchar, Fadi J., and Tomaszewski, Maciej (2019) Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics. Kidney International, 95 (3). pp. 624-635.

[img]
Preview
PDF (Published Version) - Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview
View at Publisher Website: https://doi.org/10.1016/j.kint.2018.10.0...
 
51


Abstract

Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype–Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1, PPP1R3C, LTF and TSPYL5, correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.

Item ID: 57216
Item Type: Article (Research - C1)
ISSN: 1523-1755
Keywords: aging; epigenome; genetics; kidney; transcriptome
Copyright Information: Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc.
Funders: British Heart Foundation (BHF), Kidney Research UK (KRUK), National Health and Medical Research Council Australia (NHMRC)
Projects and Grants: BHF PG/17/35/33001, KRUK RP_021_20170302, KRUK RP_017_20180302, NHMRC APP1123472
Date Deposited: 26 Feb 2019 00:32
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060404 Epigenetics (incl Genome Methylation and Epigenomics) @ 50%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060408 Genomics @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
Downloads: Total: 51
Last 12 Months: 37
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page