Proteomic and transcriptomic profiling reveal different aspects of aging in the kidney

Abstract

The kidney is an excellent model for studying organ aging. Kidney function shows steady decline with age and is easy to assay using urine or blood samples. However, little is known about the molecular changes that take place in the kidney during the aging process. In order to better understand the molecular changes that occur with age, we measured mRNA and protein levels in 188 genetically diverse mice at ages 6, 12, and 18 months. 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 highlights the role of protein homeostasis in the aging mouse heart

“…Increase in immune cell composition across multiple tissues (Moro-García et al 2013;Müller-Werdan 2007) and up-regulation of immune response genes in the aging murine heart are well documented (Bartling et al 2019;Greenig et al 2020). We observe a marked increase in complement factor genes that is also seen in our previous study of aging kidney on the same mice (Takemon et al 2021) and in the proteome of human plasma (Johnson et al 2020). Complement factor 4B (C4b) is one of the transcripts with the highest change with age in our data.…”

“…To determine if the change in correlation of proteins with age is specific to the heart we repeated this analysis on data from kidney of the same DO mice (Takemon et al 2021). In kidney, there is a modest trend of increased correlation with age for proteins (Supplemental Figure S7A), suggesting that these age-related declines in protein complex correlations are tissue-specific.…”

“…Age-related dysregulation of transcripts is offset by selective translation, and post-transcriptional mechanisms become crucial for achieving cellular homeostasis (Gonskikh and Polacek 2017). The investigation of molecular mechanisms involved in aging is further complicated by discordant age-related changes between transcripts and their corresponding proteins (Takemon et al 2021). 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 (Waldera-Lupa et al 2014).…”

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).…”