Project description:Background Aging is characterized by the gradual loss of physiological integrity, resulting in impaired function and easier death. This deterioration is a major risk factor for major human pathological diseases, including cancer, diabetes, cardiovascular disease and neurodegenerative diseases. It is very important to find biomarkers that can prevent aging. Methods Q-Exactive-MS was used for proteomic detection of young and senescence fibroblast. The key senescence-related molecules (SRMs) were identified by integrating transcriptome and proteomics from aging tissue/cells, and the correlation between these differentially expressed genes and well-known aging-related pathways. Next, we validated the expression of these molecules using qPCR, and explored the correlation between them and immune infiltrating cells. Finally, the enriched pathways of the genes significantly related to the four differential genes were identified using the single cell transcriptome. Results we first combined proteomics and transcriptome to identified four SRMs. Data sets including GSE63577, GSE64553, GSE18876, GSE85358 and qPCR confirmed that ETF1, PLBD2, ASAH1, and MOXD1 were identified as SRMs. Then the correlation between SRMs and aging-related pathways was excavated and verified. Next, we verified the expression of SRMs at the tissue level and qPCR, and explored the correlation between them and immune infiltrating cells. Finally, at the single-cell transcriptome level, we verified their expression and explored the possible pathway by which they lead to aging. Briefly, ETF1 may affect the changes of inflammatory factors such as IL-17, IL-6, and NFKB1 by indirectly regulating the enrichment and differentiation of immune cells. MOXD1 may regulate senescence by affecting the WNT pathway and changing the cell cycle. ASAH1 may affect development and regulate the phenotype of aging by affecting cell cycle-related genes. Conclusion In general, based on the analysis of proteomics and transcriptome, we identified four SRMs that may affect aging and speculated their possible mechanisms, which provides a new target for preventing aging, especially skin aging.
Project description:The evolutionarily conserved circadian system allows organisms to synchronize internal processes with 24-h cycling environmental timing cues, ensuring optimal adaptation. Like other organs, the pancreas function is under circadian control. Recent evidence suggests that aging by itself is associated with altered circadian homeostasis in different tissues which could affect the organ’s resiliency to aging-related pathologies. Pancreas pathologies of either endocrine or exocrine components are age-related. Whether pancreas circadian transcriptome output is affected by age is still unknown. To address this, here we profiled the impact of age on the pancreatic transcriptome over a full circadian cycle and elucidated a circadian transcriptome reorganization of pancreas by aging. Our study highlights gain of rhythms in the extrinsic cellular pathways in the aged pancreas and extends a potential role to fibroblast-associated mechanisms.
Project description:Cognitive decline is a common occurrence of the natural aging process in animals, and studying age-related changes in gene expression in the brain might shed light on disrupted molecular pathways that play a role in this decline. The fruit fly is a useful neurobiological model for studying aging due to its short generational time and relatively small brain size. We investigated age-dependent changes in the Drosophila melanogaster whole-brain transcriptome by comparing 5-, 20-, 30- and 40-day-old flies of both sexes. We used RNA-Sequencing of dissected brain samples followed by differential expression, temporal clustering, co-expression network and gene ontology enrichment analyses. Our study provides the first transcriptome profile of aging brains from fruit flies of both sexes, and it will serve as an important resource for those who study aging and cognitive decline in this model.
Project description:Learning and memory capability always decline with age in healthy people, and synapse loss may be an important factor contributing to this reduction. The complement pathway plays a crucial role in synaptic pruning during normal brain development, and the abnormal activation of the classical complement cascade is involved in the pathogenesis of certain neurological disorders. However, none of the past studies elucidated the effects of complement proteins in the aging of the nervous system. Here, we performed transcriptome sequencing in multiple tissues of mice at different ages in an attempt to find important regulators during aging. Our results show that the expression of complement protein C4 in the mouse brain increases with aging. In addition, we constructed different neuronal aging models for transcriptome analysis to identify the regulatory pathways upstream of complement C4, and explored the possible mechanism of complement C4 involved in synapse pruning by co-culture or immunofluorescence methods. This further demonstrates that complement C4 is a potential marker of aging. These findings suggest that NF-κB signaling pathway may contribute to age dependent complement C4 increase, which in turn affect learning and memory function via neuronal synaptic pruning regulation.
Project description:Learning and memory capability always decline with age in healthy people, and synapse loss may be an important factor contributing to this reduction. The complement pathway plays a crucial role in synaptic pruning during normal brain development, and the abnormal activation of the classical complement cascade is involved in the pathogenesis of certain neurological disorders. However, none of the past studies elucidated the effects of complement proteins in the aging of the nervous system. Here, we performed transcriptome sequencing in multiple tissues of mice at different ages in an attempt to find important regulators during aging. Our results show that the expression of complement protein C4 in the mouse brain increases with aging. In addition, we constructed different neuronal aging models for transcriptome analysis to identify the regulatory pathways upstream of complement C4, and explored the possible mechanism of complement C4 involved in synapse pruning by co-culture or immunofluorescence methods. This further demonstrates that complement C4 is a potential marker of aging. These findings suggest that NF-κB signaling pathway may contribute to age dependent complement C4 increase, which in turn affect learning and memory function via neuronal synaptic pruning regulation.