Department of Computer Science, University of Bath, Bath, United Kingdom; Department of Psychology, University of Bath, Bath, United Kingdom.
Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Prog Brain Res. 2023;275:165-215. doi: 10.1016/bs.pbr.2022.10.004. Epub 2023 Feb 3.
This chapter utilizes genomic concepts and evolutionary perspectives to further understand the possible links between typical brain aging and neurodegenerative diseases, focusing on the two most prevalent of these: Alzheimer's disease and Parkinson's disease. Aging is the major risk factor for these neurodegenerative diseases. Researching the evolutionary and molecular underpinnings of aging helps to reveal elements of the typical aging process that leave individuals more vulnerable to neurodegenerative pathologies. Very little is known about the prevalence and susceptibility of neurodegenerative diseases in nonhuman species, as only a few individuals have been observed with these neuropathologies. However, several studies have investigated the evolution of lifespan, which is closely connected with brain size in mammals, and insights can be drawn from these to enrich our understanding of neurodegeneration. This chapter explores the relationship between the typical aging process and the events in neurodegeneration. First, we examined how age-related processes can increase susceptibility to neurodegenerative diseases. Second, we assessed to what extent neurodegeneration is an accelerated form of aging. We found that while at the phenotypic level both neurodegenerative diseases and the typical aging process share some characteristics, at the molecular level they show some distinctions in their profiles, such as variation in genes and gene expression. Furthermore, neurodegeneration of the brain is associated with an earlier onset of cellular, molecular, and structural age-related changes. In conclusion, a more integrative view of the aging process, both from a molecular and an evolutionary perspective, may increase our understanding of neurodegenerative diseases.
这一章利用基因组学概念和进化观点,进一步探讨了典型脑衰老与神经退行性疾病之间可能存在的联系,重点关注其中两种最常见的疾病:阿尔茨海默病和帕金森病。衰老时这些神经退行性疾病的主要风险因素。研究衰老的进化和分子基础有助于揭示个体更容易受到神经退行性病理影响的典型衰老过程的要素。由于只有少数个体出现这些神经病理学变化,因此对于非人类物种中神经退行性疾病的流行率和易感性知之甚少。然而,已有一些研究调查了与脑大小密切相关的寿命进化,从中可以得出一些关于神经退行性变的见解。本章探讨了典型衰老过程与神经退行性事件之间的关系。首先,我们研究了与年龄相关的过程如何增加对神经退行性疾病的易感性。其次,我们评估了神经退行性变在多大程度上是衰老的加速形式。我们发现,虽然在表型水平上,神经退行性疾病和典型衰老过程具有一些共同特征,但在分子水平上,它们在其特征谱上存在一些差异,例如基因和基因表达的变化。此外,大脑的神经退行性变与更早出现与年龄相关的细胞、分子和结构变化有关。总之,从分子和进化的角度更综合地看待衰老过程,可能会增进我们对神经退行性疾病的理解。
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