Department of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
J Alzheimers Dis. 2018;62(3):1319-1335. doi: 10.3233/JAD-170732.
The Editors of the Journal of Alzheimer's Disease invited Professor Patrizia Mecocci to contribute a review article focused on the importance and implications of her research on aging, brain aging, and senile dementias over the last years. This invitation was based on an assessment that she was one of the journal's top authors and a strong supporter of the concept that oxidative stress is a major contributor to several alterations observed in age-related conditions (sarcopenia, osteoporosis) and, more significantly, in brain aging suggesting a pivotal role in the pathogenesis and progression of one of the most dramatic age-related diseases, Alzheimer's disease (AD). Her first pioneering research was on the discovery of high level of 8-hydroxy-2'-deoxyguanosine (OH8dG), a marker of oxidation in nucleic acids, in mitochondrial DNA isolated from cerebral cortex. This molecule increases progressively with aging and more in AD brain, supporting the hypothesis that oxidative stress, a condition of unbalance between the production of reactive oxygen species and antioxidants, gives a strong contribution to the high incidence of AD in old age subjects. OH8dG also increases in peripheral lymphocyte from AD subjects, suggesting that AD is not only a cerebral but also a systemic disease. The role of antioxidants, particularly vitamin E and zinc, were also studied in longevity and in cognitive decline and dementia. This review shows the main findings from Mecocci's laboratory related to oxidative stress in aging, brain aging, and AD and discusses the importance and implications of some of the major achievements in this field of research.
《阿尔茨海默病杂志》的编辑邀请帕特里齐亚·梅科奇教授撰写一篇综述文章，重点介绍她过去几年在衰老、大脑衰老和老年痴呆症研究方面的重要意义和影响。这一邀请是基于对她作为该杂志顶级作者之一的评估，以及对氧化应激是与衰老相关条件（如肌肉减少症、骨质疏松症）以及更显著的大脑衰老相关的几种变化的主要贡献的概念的强烈支持。这表明氧化应激在发病机制和进展中起着关键作用，其中最显著的与年龄相关的疾病之一是阿尔茨海默病（AD）。她的第一项开创性研究是发现 8-羟基-2'-脱氧鸟苷（OH8dG），一种核酸氧化标记物，在大脑皮层分离的线粒体 DNA 中含量较高。这种分子随着年龄的增长而逐渐增加，在 AD 大脑中增加得更多，支持了氧化应激是一种活性氧和抗氧化剂之间失衡的状态，这对老年人群中 AD 高发率有很强的贡献的假设。AD 患者外周淋巴细胞中的 OH8dG 也增加，这表明 AD 不仅是一种大脑疾病，也是一种系统性疾病。抗氧化剂，特别是维生素 E 和锌，在长寿和认知能力下降及痴呆症中的作用也得到了研究。这篇综述展示了梅科奇实验室在衰老、大脑衰老和 AD 中的氧化应激方面的主要发现，并讨论了该领域一些重大成就的重要意义和影响。
