Uddin Mohammad Nizam, Nishio Naomi, Ito Sachiko, Suzuki Haruhiko, Isobe Ken-ichi
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya University, 65 Turumai-cho, Showa-ku, Nagoya, Aichi, 466-8520, Japan.
Age (Dordr). 2012 Feb;34(1):75-85. doi: 10.1007/s11357-011-9221-9. Epub 2011 Mar 9.
Impaired or deficient autophagy is believed to cause or contribute to aging, as well as several age-related pathologies. Thymic epithelial cells had a high constitutive level of autophagy. The autophagic process may play a supporting role or even a crucial role in the presentation of self-Ags in the thymus to shape the T-cell repertoires. Autophagic activity in the liver is important for the balance of energy and nutrients for basic cell functions. The abundance of autophagic structure in both cortical and medullary thymic epithelial cells and liver with mouse age has not been examined in detail. Here, we demonstrated that the architecture of mouse thymus and liver markedly changed with age. We found that the expression of LC3 detected by immunofluorescence and Western blot analysis was greatly decreased in thymus and liver of 12-month-old mice. The same level of reduction was observed in thymus and liver of 24-month-old mice. Ultrastructure analysis by an electron microscope revealed that the number of autophagic structure/vacuole in total thymic epithelial cells and hepatocytes decrease with age. The age-related decrease of autophagic structure in thymic epithelial cells may cause the reduction of immunocompetent T-cell pool in aged mice. The age-related decrease of autophagy in liver may induce accumulation of cellular materials in liver of aged mice.
自噬受损或不足被认为会导致衰老或促使衰老,以及引发一些与年龄相关的病理状况。胸腺上皮细胞具有较高的基础自噬水平。自噬过程可能在胸腺中自身抗原的呈递以塑造T细胞库方面发挥支持作用甚至关键作用。肝脏中的自噬活性对于维持基本细胞功能所需的能量和营养平衡至关重要。随着小鼠年龄增长,皮质和髓质胸腺上皮细胞以及肝脏中自噬结构的丰度尚未得到详细研究。在此,我们证明小鼠胸腺和肝脏的结构随年龄显著改变。我们发现,通过免疫荧光和蛋白质印迹分析检测到的LC3表达在12月龄小鼠的胸腺和肝脏中大幅下降。在24月龄小鼠的胸腺和肝脏中也观察到了相同程度的下降。电子显微镜超微结构分析显示,总胸腺上皮细胞和肝细胞中自噬结构/空泡的数量随年龄减少。胸腺上皮细胞中自噬结构随年龄的减少可能导致老年小鼠免疫活性T细胞库的减少。肝脏中自噬随年龄减少可能会诱导老年小鼠肝脏中细胞物质的积累。