Lee Eun-Mi, Kim Hyun-Jung, Park Yelin, Kang Jihee Lee, Park Eun-Mi
Department of Pharmacology, College of Medicine, Ewha Womans University, Seoul 07084, Korea.
Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07084, Korea.
Korean J Physiol Pharmacol. 2025 Sep 1;29(5):559-570. doi: 10.4196/kjpp.24.372. Epub 2025 Jul 25.
Several molecules in human body exhibit light-dependent diurnal expression rhythms, and their disruption impairs physiological functions and health. Normal aging alters these rhythms, contributing to aging processes and age-related brain disorders. Chronic low-grade inflammation is a hallmark of aging (inflammaging), and age-related changes in the diurnal expression of proinflammatory cytokines have been reported in the suprachiasmatic nucleus (SCN) and peripheral blood. However, it remains unclear which genes show diurnal expression changes in brain with the SCN regions removed (extra-SCN) and whether these changes are reflected in peripheral blood. To address this, we analyzed the diurnal expression of genes in extra-SCN brain regions and cytokines in the peripheral blood of young and aged male and female mice. Samples were collected during the light (10 AM) and the dark (10 PM) phases and analyzed using RNA sequencing and cytokine array analysis. In the aged brain, the number of genes displaying diurnal variation in expression was reduced, whereas genes related to inflammation and immune responses, especially , were upregulated regardless of phase, suggesting age-associated immune dysregulation. However, peripheral blood levels of CCL21 protein did not differ between age groups. Instead, CXCL13 and IGFBP1 showed age-related diurnal alterations in the blood, but their expression patterns in the aged brain differed from those in the blood. These findings indicate that diurnal expression of inflammation-related molecules is altered with aging in both the brain and blood, with differences observed. These diurnal changes may contribute to the underlying mechanism of inflammaging and age-related diseases.
人体中的几种分子表现出光依赖性昼夜表达节律，其破坏会损害生理功能和健康。正常衰老会改变这些节律，促进衰老过程和与年龄相关的脑部疾病。慢性低度炎症是衰老（炎症衰老）的一个标志，并且在视交叉上核（SCN）和外周血中已报道促炎细胞因子的昼夜表达存在与年龄相关的变化。然而，尚不清楚在去除SCN区域的脑区（SCN外）中哪些基因显示出昼夜表达变化，以及这些变化是否在外周血中有所体现。为了解决这个问题，我们分析了年轻和老年雄性及雌性小鼠SCN外脑区基因的昼夜表达以及外周血中细胞因子的表达。在光照期（上午10点）和黑暗期（晚上10点）采集样本，并使用RNA测序和细胞因子阵列分析进行分析。在老年大脑中，表现出昼夜表达变化的基因数量减少，而与炎症和免疫反应相关的基因，尤其是 ，无论在哪个阶段均上调，这表明与年龄相关的免疫失调。然而，CCL21蛋白的外周血水平在不同年龄组之间没有差异。相反，CXCL13和IGFBP1在血液中显示出与年龄相关的昼夜变化，但其在老年大脑中的表达模式与血液中的不同。这些发现表明，炎症相关分子的昼夜表达在大脑和血液中均随衰老而改变，且存在差异。这些昼夜变化可能有助于炎症衰老和与年龄相关疾病的潜在机制。
