Fernandes Sheryl Erica, Alakesh Alakesh, Rajmani R S, Jhunjhunwala Siddharth, Saini Deepak Kumar
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
Center For BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
Biochim Biophys Acta Mol Cell Res. 2021 Aug;1868(9):119063. doi: 10.1016/j.bbamcr.2021.119063. Epub 2021 May 20.
The effects of senescence on geriatric disorders are well explored, but how it influences infections in the elderly is poorly addressed. Here, we show that several anti-microbial responses are elevated in senescent epithelial cells and old mice, which results in decreased bacterial survival in the host after infection. We identify higher levels of iNOS as a crucial host response and show that p38 MAPK in senescent epithelial cells acts as a negative regulator of iNOS transcription. However, in older mice, the ability to impede bacterial infection does not result in enhanced survival, possibly because elevated pro-inflammatory responses are not countered by a robust host protective anti-inflammatory response. Overall, while addressing an alternate advantage of senescent cells, our study demonstrates that infection-associated morbidity in the elderly may not be the sole outcome of pathogen loads but may also be influenced by the host's ability to resolve inflammation-induced damage.
衰老对老年疾病的影响已得到充分研究，但衰老如何影响老年人的感染情况却鲜有涉及。在此，我们表明，衰老的上皮细胞和老年小鼠体内的几种抗菌反应有所增强，这导致感染后宿主体内细菌存活率降低。我们确定较高水平的诱导型一氧化氮合酶（iNOS）是关键的宿主反应，并表明衰老上皮细胞中的p38丝裂原活化蛋白激酶（p38 MAPK）作为iNOS转录的负调节因子发挥作用。然而，在老年小鼠中，阻止细菌感染的能力并未导致存活率提高，这可能是因为升高的促炎反应未被强大的宿主保护性抗炎反应所抵消。总体而言，在探讨衰老细胞的另一个优势时，我们的研究表明，老年人感染相关的发病率可能并非病原体负荷的唯一结果，还可能受到宿主解决炎症诱导损伤能力的影响。
