Project description:To identify novel aging-related miRNAs, we initially established a physiological aging mouse model (20-month old male C57BL/6 mouse), compared with 2-month old male C57BL/6 mouse. Then, the Agilent miRNA microarray was performed to profile miRNA expression levels in kidney from 20-month old male C57BL/6 mouse (designated as Aging) and 2-month old male C57BL/6 mouse (designated as Young).
Project description:To monitor the mRNA expression profiling in aging process, we initially established a physiological aging mouse model (20-month old male C57BL/6 mouse), compared with 2-month old male C57BL/6 mouse. Then, the Agilent mRNA microarray was performed to profile the gene expression levels in kidney from 20-month old male C57BL/6 mouse (designated as Aging) and 2-month old male C57BL/6 mouse (designated as Young).
Project description:Studies on aging have largely included one or two OMICS layers, which may not necessarily reflect the signatures of other layers. Moreover, most aging studies have often compared very young (4-5 wks) mice with old (24 months) mice which does not reflect the aging transition after the attainment of adulthood. Therefore, we aimed to study and compared muti-OMICS aging signatures across key metabolic tissues of mature adults (6 months) and old (24 months) C57BL/6J mice (the most commonly used mouse strain). Here we compared the differentially regulated genes and enriched pathways for transcriptome, proteome and epigenome (H3K27ac, H3K4me3, H3K27me3, DNA methylation) across liver, heart, and quadriceps muscle. The major aging associated pathways cross multiple layers and tissues are decreased RNA metabolism, transcription, and translation at transcript and protein levels however increased potential of transcription at DNA methylation and H3K27ac levels.
Project description:Total ribosome-depleted RNA sequencing was performed on the left cardiac ventricle, skeletal muscle (quadriceps femoris), and kidney of young adult (16.5 wk) and early aging (86 wk) C57BL/6J mice.
Project description:Aging is accompanied by a gradual loss of systemic metabolic homeostasis, which is maintained by multiple-organs, especially the kidney and kidney. However, a systematic study of the regulatory networks and regulatory transcription factors (TFs) of aging in the kidney and kidney remains lacking. Here, we performed an integrated analysis of multi-omics datasets in the kidney and kidney from young and aged mice, including RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets, which indicated that enhanced inflammation and dysregulated metabolism were conserved signatures in aged kidney and kidney in both the transcriptome and epigenome. Transcription factor and regulatory network analysis indicated that activation of AP-1 and SPI1 was responsible for enhanced inflammation, and down-regulation of HNFs and PPARs contributed to dysregulated metabolism in aged kidney and kidney. Importantly, we found that the activation of AP-1 was cellular autonomous in aged hepatic and renal cells. However, enhanced SPI1 was caused by elevated infiltration of macrophages. Importantly, inhibition of AP-1 with small molecule combination attenuated inflammation phenotypes of aging in vivo and in vitro. Taken together, our analysis revealed common signatures and regulatory TFs of aging in the kidney and kidney, providing novel targets for the development of anti-aging interventions.
Project description:Aging is a major risk factor for chronic kidney disease. Aged mice (21 months old) exhibited enriched transcriptomic signatures of fibrosis and cellular senescence in their kidneys compared to young mice (4 months old), and dietary supplementation with nicotinamide (NAM) was insufficient to reverse these disease signatures.
Project description:Aging is a key risk factor for disease in mammals, yet its molecular basis across organs remains unclear. Here, we performed bulk RNA sequencing on eight organs (brain, heart, kidney, liver, lung, skeletal muscle, spleen, testis) from male C57BL/6J mice at distinct life stages. Our analysis revealed that age-related transcriptomic shifts vary in timing and magnitude: early in lung, spleen, testis; mid-life in heart, kidney, skeletal muscle; and late in brain and liver. Magnitude ranged from very low (testis), low (brain, heart), moderate (lungs, skeletal muscle) to high (kidneys, liver, spleen). We uncovered organ-specific aging signatures, for instance, mitochondrial and epigenetic regulation in the kidney, metabolic/detoxification in the lung, and angiogenesis as well as ribosome biogenesis in the spleen). We also identified shared transcriptomic signatures, such as cellular senescence in the kidney and skeletal muscle, ECM remodeling in the heart, skeletal muscle and spleen), or inflammation in the heart, kidney, liver and lungs. These findings highlight unique and overlapping transcriptomic aging signatures, informing future therapeutic strategies to improve healthspan.