Project description:Colon cancer is one of the leading causes of death within the western world and is linked to the aging of the colon. The disease presents differently between men and women, developing in different parts of the colon and often with a different morphology. The colonic epithelium is a rapidly renewing tissue, tasked with absorption of water and nutrients, interacting with a wide array of intestinal microbes. The gut-associated lymphoid tissue houses the majority of all immune cells. These immune cells interact with and help regulate the activity of epithelial cells. However, not much is known whether compartment-specific changes occur during aging and how said changes could impact the epithelium. Here we show that both epithelial and immune cells differ significantly between colonic compartments and experience age-related changes, with the possible causal interactions. We found a shift in the absorptive-secretory cell balance, the decrease in colonocytes possibly linked to age-associated malabsorption and intestinal disturbances. We demonstrate marked changes in the aging of the immune cells with regard to populations and interactions with epithelial cells, linking aged immune cell produced cytokines (Ifn-γ, Il1B) and the aging of colonic epithelium, which lines up with observations of inflammation causing or exacerbating age-associated gut disfunctions, such as colon cancer. Our results provide new insights into the normal and age-associated states of the colon. We anticipate our work will provide a foundation for further inquiry not only into diseases of the colon (even outside the realm of aging research) but developmental research as well.
Project description:Single-cell mRNA sequencing (mRNA-seq) technologies are reshaping the current cell-type classification system. In previous studies, we built a comprehensive mouse cell atlas to catalog all cell types by collecting scRNA-seq data in the fetal and adult stages. Howerver, systematically study for organism-level dynamic changes of cellular states across mouse life span are still lacking. Here, We made an updated version of mouse cell atlas (MCA) by adding scRNA-seq data covering 14 major mouse organs during different mouse development period. We revealed aging related regulatory networks and pathways that have not been well characterized previously. We found that the expressions of immune-related genes, such as antigen-presenting genes and immunoglobulin genes, appeared in non-immune cell types in aging process. We also focused on the expression of lung epithelial immunoglobulin genes and revealed their related transcriptional regulation mechanisms. The updated MCA resource provides a valuable resource for studying mammalian development, maturation and aging.
Project description:Aging is accompanied by the functional decline of all tissues, but it is still largely unknown how aging impacts different tissues in a cell type-specific manner. Here, we present the Aging Fly Cell Atlas (AFCA) that includes single-nucleus transcriptomes of the entire Drosophila head and body from both males and females at four different ages. We characterize 162 distinct cell types and present an in-depth analysis of cell type-specific aging features, including changes of cell composition, gene expression, number of expressed genes, transcriptome noise, and cell identity. By combining all aging features, including aging clock models predicting a cell’s age, we find cell-type specific aging patterns. Adipose tissues showed the highest aging score, followed by two cell types from the reproductive system. This transcriptomic atlas provides a valuable resource for the community to study fundamental principles of aging in complex organisms.
Project description:<p>The metabolome includes not just known but also unknown metabolites; however, metabolite annotation remains the bottleneck in untargeted metabolomics. Ion mobility – mass spectrometry (IM-MS) has emerged as a promising technology by providing multi-dimensional characterizations of metabolites. Here, we curated an ion mobility CCS atlas, namely AllCCS, and developed an integrated strategy for metabolite annotation using known or unknown chemical structures. The AllCCS atlas covers vast chemical structures with >5000 experimental CCS records and ~12 million calculated CCS values for >1.6 million small molecules. We demonstrated the high accuracy and wide applicability of AllCCS with medium relative errors of 0.5-2% for a broad spectrum of small molecules. AllCCS combined with in-silico MS/MS spectra facilitated multi-dimensional match and substantially improved the accuracy and coverage of both known and unknown metabolite annotation from biological samples. Together, AllCCS is a versatile resource that enables confident metabolite annotation, revealing comprehensive chemical and metabolic insights towards biological processes.</p><p><br></p><p><strong>Unknown Metabolite Annotation in Mouse Aging assay</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS1622' rel='noopener noreferrer' target='_blank'><strong>MTBLS1622</strong></a>.</p><p><strong>Known Metabolite Annotation in Different Biological Samples assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1693' rel='noopener noreferrer' target='_blank'><strong>MTBLS1693</strong></a>.</p>
Project description:The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remains poorly understood. To start bridging this gap, we generated a metabolome atlas of the aging mouse brain from 10 anatomical regions spanning from adolescence to late adulthood. We combined data from three chromatography-based mass spectrometry assays and structurally annotated 1,709 metabolites to reveal the underlying architecture of aging-induced changes in the brain metabolome. Overall differences between sexes were minimal. We found 94% of all metabolites to significantly differ between brain sections in at least one age group. We also discovered that 90% of the metabolome showed significant changes with respect to age groups. For example, we identified a shift in sphingolipid patterns during aging that is related to myelin remodeling in the transition from adolescent to adult brains. This shift was accompanied by large changes in overall signature in a range of other metabolic pathways. We found clear metabolic similarities in brain sections that were functionally related such as brain stem, cerebrum and cerebellum. In cerebrum, metabolic correlation patterns got markedly weaker in the transition from adolescent to ear adults, whereas correlation patterns between cerebrum and brainstem regions decreased from early to late adulthood. We were also able to map metabolic changes to gene and protein brain atlases to link molecular changes to metabolic brain phenotypes. Metabolic profiles can be investigated via https://atlas.metabolomics.us/. This new resource enables brain researchers to link new metabolomic studies to a foundation data set.
Project description:Aging is a multifactorial process with significant functional alterations of the human body including endocrinal systems which control the whole-body physiology and metabolism. In this vein, aging-induced decline of endocrine function are associated with multiple physiological and metabolic diseases. However, aging-associated molecular shifts in the pituitary gland, the central organ of the endocrine system, have not been dissected systemically. In this study, we conducted single-cell transcriptomic analysis of the anterior pituitary gland by comparing old and young male mice. Single-cell transcriptomics not only increased the resolution for clustering of various cell types in the pituitary gland, but also enabled detailed analysis of differential expression and intercellular communication caused by aging. In summary, our study constructed the first single-cell transcriptomic atlas of pituitary aging and identified associated features of in a single-cell level, providing resources to develop novel potential therapeutic targets for aging-associated endocrine dysfunction.
Project description:The airways conduct gases to and from the gas-exchanging alveoli of the lung and are the site of age-related diseases, such as chronic obstructive pulmonary disease, asthma, and bronchogenic carcinoma. Here we set out to study the effects of aging on the cellular composition and gene expression of murine airway. We present a comprehensive single-cell RNA-sequencing atlas of tracheas from young (2 month) and aged (24 month) mice, comprising diverse populations of cells, including epithelial, endothelial, immune, fibroblast, and cartilage cells.