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Aging-associated gene expression profiling in adipose tissue derived mesenchymal stem cells.

ABSTRACT: Background & Aims: Recently, energy metabolism in adipose tissue has been the subject of renewed interest, because significant energy expenditure can be induced in cells derived from white adipose tissue derived mesenchymal stem cells (Ad-MSCs) as beige adipocytes (BA), in addition to brown adipose tissue. Here we evaluated whether age-related changes in Ad-MSCs affect on impaired energy homeostasis and progressive obesity-related diseases. Materials and Methods: We isolated Ad-MSCs from subcutaneous murine fat tissues fed with control chow (C) or high-fat diet (60% fat; HF) for 12 or 24 weeks (younger or older groups, respectively). After two to three times passage, we performed the cellular characteristics analyses, which included differentiation property, flow cytometric and microarray analyses. Results: Ad-MSCs from older mice showed impaired differentiation capacity into BAs compared to the cells from younger mice. Global gene expression analysis by microarray revealed several genes involved with the browning of white adipose tissue were down-regulated according to aging. Additionally, HF feeding promoted aging-associated characteristic changes in Ad-MSCs. Conclusion: These results indicate the compensation potential of Ad-MSCs on energy homeostasis is affected by aging and dietary factors. A new approach targeting Ad-MSCs might represent a potential strategy for the prevention of obesity-related diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE115068 | GEO | 2019/07/17

REPOSITORIES: GEO

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Project description:Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan; however, the mosaic of molecular changes responsible CR benefits remain unclear, particularly in brain regions susceptible to deterioration throughout aging. Thus, we examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimerâs disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses an age-dependent signature of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger- (5 months) and older-adult (15 months) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa proteins 1b and 5 (Hspa1b and Hspa5), protein disulfide isomerase family A members 4 and 6 (Pdia4 and Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR throughout adulthood, although the global CR-specific expression profiles at young and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within hippocampal CA1 throughout aging. Hippocampal CA1 region mRNA profiles of younger- (5 months) and older-adult (15 months) mice on calorie-restricted (CR) and normal (AD) diets were generated by deep sequencing using Illumina HiSeq 2500.

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Aging-associated gene expression profiling in adipose tissue derived mesenchymal stem cells.

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