Project description:Aging causes a functional decline in tissues throughout the body that may be delayed by caloric restriction (CR). However, the cellular profiles and signatures of aging, as well as those ameliorated by CR, remain unclear. Here, we built comprehensive single-cell and single-nucleus transcriptomic atlases across various rat tissues undergoing aging and CR. CR attenuated aging-related changes in cell type composition, gene expression, and core transcriptional regulatory networks. Immune cells were increased during aging, and CR favorably reversed the aging-disturbed immune ecosystem. Computational prediction revealed that the abnormal cell-cell communication patterns observed during aging, including the excessive proinflammatory ligand-receptor interplay, were reversed by CR. Our work provides multi-tissue single-cell transcriptional landscapes associated with aging and CR in a mammal, enhances our understanding of the robustness of CR as a geroprotective intervention, and uncovers how metabolic intervention can act upon the immune system to modify the process of aging.
Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes
Project description:Sarcopenia is the decreased muscle mass and weakness associated with aging and a major cause of morbidity and mortality in the elderly. To what extent non-locomotive muscles are susceptible to this condition is unclear. For example, age affects laryngeal function (ventilation, airway protective reflexes, swallowing and phonation). Age-related laryngeal dysfunction may be due to effects on its intrinsic muscles that have a unique phenotype: very small, mostly fast oxidative muscle fibers. For this study, we examined how age alters the functional characteristics and gene expression profile of posterior cricoarytenoid (PCA), an intrinsic laryngeal muscle. PCA muscles from Fischer 344-Brown Norway F1 hybrid rats (6 and 30 months of age) were used for cDNA microarrays, light and electron (EM) microscopy, and in vitro contractile function. Histological analyses demonstrated a ~40% increase in mean PCA fiber size and in the number of fibers with low myosin ATPase activity. There was also evidence of ragged-red fibers, a hallmark of mitochondrial dysfunction. In turn, mitochondrial volume density, determined by EM, was significantly higher in PCA muscles at 30 months (43% vs. 21% at 6 months). In vitro function showed a decrease in velocity of unloaded shortening at 30 months. Finally, cDNA microarrays demonstrated a transcriptome shift in PCA muscle with age. Gene classes with the largest changes were: signal transduction, transcription factors, and metabolic enzymes. These data demonstrate that PCA muscles are significantly altered by age. Moreover, the observed changes in muscle fiber size, mitochondrial content and gene expression profile suggest that the PCA response to age diverges from that seen in more typical skeletal muscles. Keywords: aging, time course