Department of Geriatrics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China.
JCI Insight. 2024 Mar 8;9(5):e167676. doi: 10.1172/jci.insight.167676.
Colon cancer affects people of all ages. However, its frequency, as well as the related morbidity and mortality, are high among older adults. The complex physiological changes in the aging gut substantially limit the development of cancer therapies. Here, we identify a potentially unique intestinal microenvironment that is linked with an increased risk of colon cancer in older adults. Our findings show that aging markedly influenced persistent fucosylation of the apical surfaces of intestinal epithelial cells, which resulted in a favorable environment for tumor growth. Furthermore, our findings shed light on the importance of the host-commensal interaction, which facilitates the dysregulation of fucosylation and promotes tumor growth as people get older. We analyzed colonic microbial populations at the species level to find changes associated with aging that could contribute to the development of colon cancer. Analysis of single-cell RNA-sequencing data from previous publications identified distinct epithelial cell subtypes involved in dysregulated fucosylation in older adults. Overall, our study provides compelling evidence that excessive fucosylation is associated with the development of colon cancer, that age-related changes increase vulnerability to colon cancer, and that a dysbiosis in microbial diversity and metabolic changes in the homeostasis of older mice dysregulate fucosylation levels with age.
结肠癌影响所有年龄段的人。然而，其发病率以及相关的发病率和死亡率在老年人中较高。衰老肠道的复杂生理变化极大地限制了癌症治疗的发展。在这里，我们确定了一个潜在的独特的肠道微环境，与老年人中结肠癌风险的增加有关。我们的研究结果表明，衰老显著影响了肠道上皮细胞顶表面的持续性岩藻糖基化，从而为肿瘤生长创造了有利的环境。此外，我们的研究结果揭示了宿主-共生相互作用的重要性，它促进了岩藻糖基化的失调，并随着年龄的增长促进肿瘤的生长。我们分析了结肠微生物种群的物种水平，以找到与衰老相关的变化，这些变化可能导致结肠癌的发生。对以前发表的单细胞 RNA 测序数据的分析确定了在老年人中涉及失调岩藻糖基化的不同上皮细胞亚型。总的来说，我们的研究提供了令人信服的证据，表明过度岩藻糖基化与结肠癌的发生有关，与年龄相关的变化增加了结肠癌的易感性，并且老年小鼠的微生物多样性失调和内稳态中的代谢变化导致了岩藻糖基化水平随年龄的变化。
