Abstract：
Aging significantly influences cellular activity and metabolism in glucose-responsive tissues, yet a comprehensive evaluation of the impacts of aging and associated cell-type responses has been lacking. This study integrates transcriptomic, methylomic, single-cell RNA sequencing, and metabolomic data to investigate aging-related regulations in adipose and muscle tissues. Through coexpression network analysis of the adipose tissue, we identified aging-associated network modules specific to certain cell types, including adipocytes and immune cells. Aging upregulates the metabolic functions of lysosomes and downregulates the branched-chain amino acids (BCAAs) degradation pathway. Additionally, aging-associated changes in cell proportions, methylation profiles, and single-cell expressions were observed in the adipose. In the muscle tissue, aging was found to repress the metabolic processes of glycolysis and oxidative phosphorylation, along with reduced gene activity of fast-twitch type II muscle fibers. Metabolomic profiling linked aging-related alterations in plasma metabolites to gene expression in glucose-responsive tissues, particularly in tRNA modifications, BCAA metabolism, and sex hormone signaling. Together, our multi-omic analyses provide a comprehensive understanding of the impacts of aging on glucose-responsive tissues and identify potential plasma biomarkers for these effects.
摘要：
衰老显着影响葡萄糖响应组织的细胞活性和代谢，然而，缺乏对衰老和相关细胞类型反应的影响的全面评估。这项研究整合了转录组学，甲基，单细胞RNA测序，和代谢组学数据来研究脂肪和肌肉组织中与衰老相关的规律。通过对脂肪组织的共表达网络分析,我们确定了特定于某些细胞类型的老化相关网络模块，包括脂肪细胞和免疫细胞。老化上调溶酶体的代谢功能并下调支链氨基酸(BCAAs)降解途径。此外,细胞比例的衰老相关变化，甲基化谱，在脂肪中观察到单细胞表达。在肌肉组织中，发现衰老抑制糖酵解和氧化磷酸化的代谢过程，随着快速抽搐II型肌纤维的基因活性降低。代谢组学分析将血浆代谢物的衰老相关改变与葡萄糖反应性组织中的基因表达联系起来，特别是在tRNA修饰中，BCAA代谢，和性激素信号。一起,我们的多组学分析提供了对衰老对葡萄糖反应性组织的影响的全面理解,并确定了这些影响的潜在血浆生物标志物.
