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

Adult Aged Aged, 80 and over Aging / genetics Computational Biology DNA Methylation / genetics Epigenomics Female Gene Expression Profiling Genetic Variation Glomerular Filtration Rate / physiology Humans Intracellular Signaling Peptides and Proteins / genetics Lactoferrin / genetics Male Middle Aged Muramidase / genetics Nephrons / pathology Nuclear Proteins / genetics RNA-Seq Renal Insufficiency, Chronic / genetics Transcriptome / genetics

aging epigenome genetics kidney transcriptome

Journal

Kidney international

ISSN: 1523-1755

Titre abrégé: Kidney Int

Pays: United States

ID NLM: 0323470

Informations de publication

Date de publication:
03 2019

Historique:

received: 02 04 2018

revised: 15 10 2018

accepted: 18 10 2018

entrez: 21 2 2019

pubmed: 21 2 2019

medline: 15 2 2020

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.kint.2018.10.029 PMID: 30784661 PMC: PMC6390171

pubmed: 30784661

pii: S0085-2538(18)30837-8

doi: 10.1016/j.kint.2018.10.029

pmc: PMC6390171

pii:

doi:

Substances chimiques

Intracellular Signaling Peptides and Proteins 0

LTF protein, human 0

Nuclear Proteins 0

PPP1R3C protein, human 0

TSPYL5 protein, human 0

Muramidase EC 3.2.1.17

Lactoferrin EC 3.4.21.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

624-635

Subventions

Organisme : British Heart Foundation

ID : PG/17/35/33001

Pays : United Kingdom

Organisme : British Heart Foundation

ID : PG/17/35/33001

Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

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