Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania.
Department of Psycho-Neurosciences and Rehabilitation, University of Oradea, 410087 Oradea, Romania.
Int J Mol Sci. 2024 Sep 30;25(19):10535. doi: 10.3390/ijms251910535.
Progress made by the medical community in increasing lifespans comes with the costs of increasing the incidence and prevalence of age-related diseases, neurodegenerative ones included. Aging is associated with a series of morphological changes at the tissue and cellular levels in the brain, as well as impairments in signaling pathways and gene transcription, which lead to synaptic dysfunction and cognitive decline. Although we are not able to pinpoint the exact differences between healthy aging and neurodegeneration, research increasingly highlights the involvement of neuroinflammation and chronic systemic inflammation (inflammaging) in the development of age-associated impairments via a series of pathogenic cascades, triggered by dysfunctions of the circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender differences in the susceptibility and course of neurodegeneration that appear to be mediated by glial cells emphasize the need for future research in this area and an individualized therapeutic approach. Although rejuvenation research is still in its very early infancy, accumulated knowledge on the various signaling pathways involved in promoting cellular senescence opens the perspective of interfering with these pathways and preventing or delaying senescence.
医学界在延长寿命方面取得的进展伴随着与年龄相关的疾病(包括神经退行性疾病)发病率和患病率上升的代价。衰老与大脑组织和细胞水平的一系列形态变化以及信号通路和基因转录的损伤有关,这些变化导致突触功能障碍和认知能力下降。尽管我们无法准确指出健康衰老和神经退行性变之间的确切区别,但越来越多的研究强调了神经炎症和慢性系统性炎症(炎症衰老)通过一系列致病级联反应在与年龄相关的损伤发展中的作用,这些级联反应是由生物钟功能障碍、肠道菌群失调、免疫衰老或胆碱能信号转导受损引发的。此外,神经退行性变易感性和病程中的性别差异似乎是由神经胶质细胞介导的,这强调了未来在这一领域进行研究和采取个体化治疗方法的必要性。尽管衰老研究仍处于起步阶段,但关于促进细胞衰老的各种信号通路的知识积累为干预这些通路以及预防或延缓衰老提供了新的视角。