College of Animal Science, Guangdong Laboratory for Lingnan Modern Agriculture/Guangdong Provincial Key Laboratory of Animal Nutrition Control/National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, 510642, Guangdong, China.
Stem Cell Rev Rep. 2021 Jun;17(3):842-849. doi: 10.1007/s12015-020-10073-y. Epub 2020 Nov 17.
The intestine integrates the function of digestion, absorption, and barrier, which is easily damaged by the external factors upon ageing. The intestinal stem cells (ISCs) exist at the intestinal crypt base and play an indispensable role in intestinal homeostasis and regeneration. The intestine ageing contributes to malabsorption and other associated illnesses, which were considered to be related to ISCs. Here, we summarize the current research progress of mammalian ISCs ageing and pay more attention to the central regulatory role of the mTORC1 signaling pathway in regulating mammalian ISCs ageing, and its related AMPK, FOXO, Wnt signaling pathways. Furthermore, we also discuss the interventions aimed at mTORC1 and its associated signaling pathways, which may provide potential strategies for rejuvenating aged ISCs and the therapy of age-related intestinal diseases. Graphical abstract Many signaling pathways are altered in the ageing ISCs, thereby inducing the decrease of ISC self-renewal, differentiation, and regeneration, an increasing of oxidative stress may contribute to damage to the ISCs. Interventions such as calorie restriction, fasting and so on can effectively alleviate these adverse effects.
肠道整合了消化、吸收和屏障功能，容易在衰老过程中受到外部因素的损害。肠道干细胞（ISCs）存在于肠隐窝底部，在肠道稳态和再生中发挥着不可或缺的作用。肠道衰老导致吸收不良和其他相关疾病，这些疾病被认为与 ISCs 有关。在这里，我们总结了哺乳动物 ISCs 衰老的最新研究进展，并更加关注 mTORC1 信号通路在调节哺乳动物 ISCs 衰老及其相关 AMPK、FOXO、Wnt 信号通路中的核心调控作用。此外，我们还讨论了针对 mTORC1 及其相关信号通路的干预措施，这可能为恢复衰老的 ISCs 和治疗与年龄相关的肠道疾病提供潜在的策略。 图表摘要 在衰老的 ISCs 中，许多信号通路发生改变，从而导致 ISC 自我更新、分化和再生减少，氧化应激增加可能导致 ISCs 损伤。热量限制、禁食等干预措施可以有效缓解这些不利影响。
