Receptor Biology Lab, University of Antwerp, 2610 Antwerpen, Belgium.
Moffitt Cancer Center, Department of Metabolism & Physiology, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Int J Mol Sci. 2023 May 9;24(10):8499. doi: 10.3390/ijms24108499.
G protein-coupled receptors (GPCRs) play a significant role in controlling biological paradigms such as aging and aging-related disease. We have previously identified receptor signaling systems that are specifically associated with controlling molecular pathologies associated with the aging process. Here, we have identified a pseudo-orphan GPCR, G protein-coupled receptor 19 (GPR19), that is sensitive to many molecular aspects of the aging process. Through an in-depth molecular investigation process that involved proteomic, molecular biological, and advanced informatic experimentation, this study found that the functionality of GPR19 is specifically linked to sensory, protective, and remedial signaling systems associated with aging-related pathology. This study suggests that the activity of this receptor may play a role in mitigating the effects of aging-related pathology by promoting protective and remedial signaling systems. GPR19 expression variation demonstrates variability in the molecular activity in this larger process. At low expression levels in HEK293 cells, GPR19 expression regulates signaling paradigms linked with stress responses and metabolic responses to these. At higher expression levels, GPR19 expression co-regulates systems involved in sensing and repairing DNA damage, while at the highest levels of GPR19 expression, a functional link to processes of cellular senescence is seen. In this manner, GPR19 may function as a coordinator of aging-associated metabolic dysfunction, stress response, DNA integrity management, and eventual senescence.
G 蛋白偶联受体（GPCRs）在控制衰老和与衰老相关的疾病等生物学范式方面发挥着重要作用。我们之前已经确定了与控制与衰老过程相关的分子病理学相关的受体信号系统。在这里，我们已经确定了一种伪孤儿 GPCR，G 蛋白偶联受体 19（GPR19），它对衰老过程的许多分子方面都很敏感。通过涉及蛋白质组学、分子生物学和先进信息学实验的深入分子研究过程，这项研究发现 GPR19 的功能与与衰老相关的病理学相关的感觉、保护和补救信号系统特别相关。这项研究表明，该受体的活性可能通过促进保护和补救信号系统在减轻与衰老相关的病理学的影响方面发挥作用。GPR19 表达的变化表明在这个更大的过程中分子活性的可变性。在 HEK293 细胞中的低表达水平下，GPR19 表达调节与应激反应和对这些反应的代谢反应相关的信号范式。在更高的表达水平下，GPR19 表达共同调节参与感知和修复 DNA 损伤的系统，而在 GPR19 表达的最高水平下，观察到与细胞衰老过程的功能联系。以这种方式，GPR19 可以作为与衰老相关的代谢功能障碍、应激反应、DNA 完整性管理和最终衰老的协调者。
