Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Department of Life Science and Chemistry, Graduate School of Natural Science and Technology, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Exp Gerontol. 2020 Dec;142:111099. doi: 10.1016/j.exger.2020.111099. Epub 2020 Oct 1.
Impairment of gastrointestinal function and reduction of nutrient absorption associated with aging contribute to increased risk of malnutrition in the elderly population, resulting in physical weakness and vulnerability to disease. The present study was performed to examine the relationships between aging-associated morphological changes of the small intestine and nutrient malabsorption using senescence-accelerated mouse prone 8 (SAMP8) mice. Comparison of the morphology of the small intestine of young (22-week-old) and senescent (43-week-old) SAMP8 mice showed no significant changes in villus length, while the mRNA expression levels of secretory cell marker genes were significantly reduced in senescent mice. In addition, crypts recovered from the small intestine of senescent mice showed a good capacity to form intestinal organoids ex vivo, suggesting that the regenerative capacity of intestinal stem cells (ISCs) was unaffected by accelerated senescence. These results indicated that changes induced by accelerated senescence in the small intestine of SAMP8 mice are different from changes reported previously in normal aging mouse models. Biochemical analyses of serum before and during senescence also indicated that senescent SAMP8 mice are not in a malabsorption state. Furthermore, a diet supplemented with persimmon pectin had a mild effect on the small intestine of senescent SAMP8 mice. Intestinal villus length was slightly increased in the medial part of the small intestine of pectin-fed mice. In contrast, intestinal crypt formation capacity was enhanced by the pectin diet. Organoid culture derived from the small intestine of mice fed pectin exhibited a greater number of lobes per organoid compared with those from mice fed a control diet, and Lyz1 and Olfm4 mRNA levels were significantly increased. In conclusion, accelerated senescence induced exclusive changes in the small intestine, which were not related to nutrient malabsorption. Therefore, the SAMP8 strain may not be a suitable model to evaluate the effects of aging on intestinal homeostasis and nutrient absorption impairment.
与衰老相关的胃肠道功能障碍和营养吸收减少导致老年人群营养风险增加，使他们身体虚弱，易患疾病。本研究旨在使用快速老化模型小鼠（SAMP8）研究与衰老相关的小肠形态变化与营养吸收不良之间的关系。比较年轻（22 周龄）和衰老（43 周龄）SAMP8 小鼠的小肠形态，发现绒毛长度没有明显变化，而衰老小鼠的分泌细胞标记基因的 mRNA 表达水平显著降低。此外，从衰老小鼠小肠中回收的隐窝在体外具有良好的形成肠类器官的能力，这表明肠干细胞（ISCs）的再生能力不受加速衰老的影响。这些结果表明，SAMP8 小鼠小肠中加速衰老引起的变化与以前在正常衰老小鼠模型中报道的变化不同。衰老前后血清的生化分析也表明衰老的 SAMP8 小鼠没有处于吸收不良状态。此外，柿子果胶饮食对衰老 SAMP8 小鼠的小肠有轻微作用。果胶喂养的小鼠小肠中段的肠绒毛长度略有增加。相比之下，果胶饮食增强了肠隐窝形成能力。来自喂食果胶的小鼠小肠的类器官培养物每个类器官的小叶数量明显多于喂食对照饮食的小鼠，并且 Lyz1 和 Olfm4 的 mRNA 水平显著增加。总之，加速衰老诱导了小肠的独特变化，这些变化与营养吸收不良无关。因此，SAMP8 品系可能不是评估衰老对肠道内稳态和营养吸收障碍影响的合适模型。
