Atlas of the aging mouse colon

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-gamma, 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. Single-cell RNA seq on epithelial and immune cells from the mouse colon结肠癌是西方世界主要致死病因之一，且与结肠衰老密切相关。该疾病在男女群体中表现存在差异，可发生于结肠的不同部位，且通常具有不同的形态学特征。 结肠上皮是一类快速更新的组织，负责水分与营养物质的吸收，并与多样的肠道微生物群相互作用。肠道相关淋巴组织（gut-associated lymphoid tissue）容纳了体内绝大多数免疫细胞，这些免疫细胞可与上皮细胞互动并协助调控其功能。然而，目前学界对衰老过程中是否存在组织分区特异性的改变，以及此类改变如何影响上皮细胞的机制仍知之甚少。 本研究证实，结肠不同分区的上皮细胞与免疫细胞均存在显著差异，并随衰老发生特征性改变，且二者间可能存在因果互作关系。我们发现吸收-分泌细胞的平衡发生偏移，结肠上皮细胞数量减少可能与衰老相关的吸收不良及肠道功能紊乱存在关联。本研究还揭示了免疫细胞衰老在细胞群组成及与上皮细胞互作方面的显著变化，将衰老免疫细胞分泌的细胞因子（干扰素-γ（Ifn-gamma）、白细胞介素1β（Il1B））与结肠上皮衰老联系起来，这与“炎症可诱发或加重衰老相关肠道功能障碍（如结肠癌）”的已有研究结果相符。 本研究结果为结肠的正常生理状态及衰老相关病理状态提供了全新的认知。我们期望本研究不仅可为结肠疾病（甚至超出衰老研究范畴的结肠疾病）的后续探究，也可为发育相关研究奠定基础。 本研究针对小鼠结肠的上皮细胞与免疫细胞开展了单细胞RNA测序（single-cell RNA seq）。