Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea.
Aging Cell. 2010 Apr;9(2):243-51. doi: 10.1111/j.1474-9726.2010.00554.x. Epub 2010 Jan 20.
Elderly individuals have an increased susceptibility to microbial infections because of age-related anatomical, physiological, and environmental factors. However, the mechanism of aging-dependent susceptibility to infection is not fully understood. Here, we found that caveolae-dependent endocytosis is elevated in senescent cells. Thus, we focused on the implications of caveolae-dependent endocytosis using Salmonella typhimurium, which causes a variety of diseases in humans and animals by invading the eukaryotic host cell. Salmonella invasion increased in nonphagocytotic senescent host cells in which caveolin-1 was also increased. When caveolae structures were disrupted by methyl-beta-cyclodextrin or siRNA of caveolin-1 in the senescent cells, Salmonellae invasion was reduced markedly compared to that in nonsenescent cells. In contrast, the over-expression of caveolin-1 led to increased Salmonellae invasion in nonsenescent cells. Moreover, in aged mice, caveolin-1 was found to be highly expressed in Peyer's patch and spleen, which are targets for infection by Salmonellae. These results suggest that high levels of caveolae and caveolin-1 in senescent host cells might be related to the increased susceptibility of elderly individuals to microbial infections.
老年人由于与年龄相关的解剖学、生理学和环境因素，易受到微生物感染。然而，衰老相关易感性感染的机制尚未完全阐明。在这里，我们发现衰老细胞中依赖于 caveolae 的内吞作用升高。因此，我们使用沙门氏菌（Salmonella typhimurium）专注于依赖于 caveolae 的内吞作用的意义，沙门氏菌通过入侵真核宿主细胞而在人类和动物中引起多种疾病。沙门氏菌入侵在非吞噬性衰老宿主细胞中增加，其中 caveolin-1 也增加。当 caveolae 结构在衰老细胞中被甲基-β-环糊精或 caveolin-1 的 siRNA 破坏时，沙门氏菌的入侵明显低于非衰老细胞。相比之下，caveolin-1 的过表达导致非衰老细胞中沙门氏菌的入侵增加。此外，在老年小鼠中，发现 caveolin-1 在派尔集合淋巴结（Peyer's patch）和脾脏中高度表达，这是沙门氏菌感染的靶标。这些结果表明，衰老宿主细胞中高水平的 caveolae 和 caveolin-1 可能与老年人易受微生物感染有关。
