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.

Genome-wide transcript and protein analysis reveals distinct features of aging in the mouse heart

“…By analyzing both transcripts and proteins in the mouse heart we were able to detect distinct biological processes that are altered through the course of natural aging. We and others have found that age-related transcriptional changes are not necessarily followed by a change in their proteins and likewise, age-related changes in proteins are not preceded by transcriptional changes (12,13,62,80). We found that transcripts decreasing in expression with age are associated with cardiomyocyte contraction and survival, and fatty-acid metabolism.…”

“…Age-related dysregulation of transcripts is offset by selective translation, and post-transcriptional mechanisms become crucial for achieving cellular homeostasis (11). The investigation of molecular mechanisms involved in aging is further complicated by the uncoupling of age-related changes between transcripts and their corresponding proteins (12). Waldera-Lupa et al (2014) found that 77% of the proteins that change with age in human fibroblasts showed no corresponding change in their transcripts (13).…”

Misexpression of genes lacking CpG islands drives degenerative changes during aging

“…To understand how expression of CGI + and CGI − genes (table S2) changes during aging, we performed RNA sequencing (RNA-seq) of kidneys and hearts from diversity outbred (DO) mice. DO mice are a genetically diverse mouse resource that mimics the complexity of the human population with variable rates of physiological aging ( 12 , 13 ). Figure 1B shows an example of gene expression in kidneys from 18- and 6-month-old mice, where 33.71% of CGI − genes were up-regulated over twofold in the aged kidney compared to the young kidney.…”

Single-nuclear transcriptomics reveals diversity of proximal tubule cell states in a dynamic response to acute kidney injury

“…Since the phenotype of a senescent cell is dynamic and heterogeneous depending on the type of senescence inducer, and on the cell and tissue type, we compared our data with transcriptomic signatures characteristic of the aging kidney and senescent cells and/or SASP, in various cell types subjected to different methods of senescence induction (Fig. 4E) (58)(59)(60)(61)(62)(63)(64). The "senescence core signatures" identified by Hernandez-Segura et al (62) in fibroblasts, keratinocytes, melanocytes and astrocytes and by Casella et al (63) in fibroblasts and endothelial cells were not enriched in late injured cells.…”