Proteomic and transcriptomic profiling reveal different aspects of aging in the kidney
Abstract
Little is known about the molecular changes that take place in the kidney during the aging process. In order to better understand these changes, we measured mRNA and protein levels in genetically diverse mice at different ages. We observed distinctive change in mRNA and protein levels as a function of age. Changes in both mRNA and protein are associated with increased immune infiltration and decreases in mitochondrial function. Proteins show a greater extent of change and reveal changes in a wide array of biological processes including unique, organ-specific features of aging in kidney. Most importantly, we observed functionally important age-related changes in protein that occur in the absence of corresponding changes in mRNA. Our findings suggest that mRNA profiling alone provides an incomplete picture of molecular aging in the kidney and that examination of changes in proteins is essential to understand aging processes that are not transcriptionally regulated.
Data availability
Source data and analysis scripts have been deposited with FigShare (10.6084/m9.figshare. 12894146). In addition, the transcript and protein data are available in an online tool that supports genetic mapping analysis (https://churchilllab.jax.org/qtlviewer/JAC/DOKidney).The RNA-seq data have been deposited in NCBI's Gene Expression Omnibus, accession number GSE121330 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE121330). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD023823.
-
Transcriptomic profiling reveals distinct modes of aging in the kidneyNCBI Gene Expression Omnibus, GSE121330.
Article and author information
Author details
Funding
National Institutes of Health (AG038070)
- Ron Korstanje
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The Jackson Laboratory's Institutional Animal Care and Use Committee approved all reported mouse studies.(AUS#06005).
Copyright
© 2021, Takemon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 8,532
- views
-
- 1,014
- downloads
-
- 81
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Computational and Systems Biology
- Physics of Living Systems
Explaining biodiversity is a fundamental issue in ecology. A long-standing puzzle lies in the paradox of the plankton: many species of plankton feeding on a limited variety of resources coexist, apparently flouting the competitive exclusion principle (CEP), which holds that the number of predator (consumer) species cannot exceed that of the resources at a steady state. Here, we present a mechanistic model and demonstrate that intraspecific interference among the consumers enables a plethora of consumer species to coexist at constant population densities with only one or a handful of resource species. This facilitated biodiversity is resistant to stochasticity, either with the stochastic simulation algorithm or individual-based modeling. Our model naturally explains the classical experiments that invalidate the CEP, quantitatively illustrates the universal S-shaped pattern of the rank-abundance curves across a wide range of ecological communities, and can be broadly used to resolve the mystery of biodiversity in many natural ecosystems.
-
- Chromosomes and Gene Expression
- Computational and Systems Biology
Genes are often regulated by multiple enhancers. It is poorly understood how the individual enhancer activities are combined to control promoter activity. Anecdotal evidence has shown that enhancers can combine sub-additively, additively, synergistically, or redundantly. However, it is not clear which of these modes are more frequent in mammalian genomes. Here, we systematically tested how pairs of enhancers activate promoters using a three-way combinatorial reporter assay in mouse embryonic stem cells. By assaying about 69,000 enhancer-enhancer-promoter combinations we found that enhancer pairs generally combine near-additively. This behaviour was conserved across seven developmental promoters tested. Surprisingly, these promoters scale the enhancer signals in a non-linear manner that depends on promoter strength. A housekeeping promoter showed an overall different response to enhancer pairs, and a smaller dynamic range. Thus, our data indicate that enhancers mostly act additively, but promoters transform their collective effect non-linearly.