Pesce Mirko, Tatangelo Raffaella, La Fratta Irene, Rizzuto Alessia, Campagna Giovanna, Turli Cinzia, Ferrone Alessio, Franceschelli Sara, Speranza Lorenza, Verrocchio Maria C, De Lutiis Maria A, Felaco Mario, Grilli Alfredo
School of Medicine and Health Science, University G. D'AnnunzioChieti, Italy.
Front Mol Neurosci. 2017 Jul 24;10:233. doi: 10.3389/fnmol.2017.00233. eCollection 2017.
Aging cognitive decline has been associated to impairment of the Hypothalamus Pituitary Adrenals (HPA) axis activity and a higher level of the systemic inflammation. However, little is known about the molecules driving this process at peripheral level. In addition, the cognitive function is to some extent modifiable with Memory Training (MT) programs, even among older adults and beyond. The study aims to evaluate whether MT could contribute to ameliorate cognitive performance and modulate the HPA axis activity as well the low level inflammation in the aging phenotype. Whether the phosphatase WIP-1, a negative regulator for inflammation, is involved in this process was also investigated. We recruited 31 young adults (19-28, years of age) and 62 older adults aged over 60. Thirty-two older adults were submitted to 6-months of MT program (EG), and 28 older adults were no treated and used as Control Group (CG). Global cognitive functioning (MMSE score), verbal and visual memory, and attention were assessed at baseline (T0) and after 6-months (T1). At the same time, plasmatic level of Cortisol (C), IL-1β, IL-18, IL-6, and the expression of WIP-1 mRNA and protein in Peripheral Blood Mononuclear Cells were analyzed in young adults at T0, as well in older adults at T0 and T1. Together, the results suggest that MT improves the global cognitive functionality, verbal and visual memory, as well as the level of attention. At the same time we observed a decrease of the plasmatic level of C, of the cytokines, and an increase of the expression of mRNA and protein of WIP-1. The analysis of correlations highlighted that the level of the mRNA of WIP-1 was positively associated to the MMSE score, and negatively to the C and cytokine levels. In conclusion, we purpose the MT as tool that could help support successful aging through the improving of memory, attention and global cognitive function performance. Furthermore, this approach could participate to maintain lower the peripheral levels of the C and pro-inflammatory cytokines. The WIP-1 as a potential new target of the pathophysiology of aging is theorized.
衰老认知衰退与下丘脑 - 垂体 - 肾上腺（HPA）轴活动受损及全身炎症水平升高有关。然而，关于在外周水平驱动这一过程的分子却知之甚少。此外，认知功能在一定程度上可通过记忆训练（MT）计划得到改善，即使是在老年人及以上人群中。该研究旨在评估MT是否有助于改善认知表现，并调节衰老表型中的HPA轴活动以及低水平炎症。还研究了磷酸酶WIP - 1（一种炎症负调节因子）是否参与此过程。我们招募了31名年轻成年人（19 - 28岁）和62名60岁以上的老年人。32名老年人接受了为期6个月的MT计划（实验组，EG），28名老年人未接受治疗并用作对照组（CG）。在基线（T0）和6个月后（T1）评估整体认知功能（MMSE评分）、言语和视觉记忆以及注意力。同时，分析了年轻成年人在T0时以及老年人在T0和T1时外周血单核细胞中皮质醇（C）、IL - 1β、IL - 18、IL - 6的血浆水平以及WIP - 1 mRNA和蛋白的表达。总之，结果表明MT改善了整体认知功能、言语和视觉记忆以及注意力水平。同时，我们观察到血浆C水平、细胞因子水平下降，WIP - 1的mRNA和蛋白表达增加。相关性分析突出显示，WIP - 1的mRNA水平与MMSE评分呈正相关，与C和细胞因子水平呈负相关。总之，我们提出MT作为一种工具，可通过改善记忆、注意力和整体认知功能表现来帮助支持成功衰老。此外，这种方法可能有助于维持较低的外周C和促炎细胞因子水平。理论上认为WIP - 1是衰老病理生理学的一个潜在新靶点。
