A comprehensive multiomics approach toward understanding the relationship between aging and dementia.
A comprehensive multiomics approach toward understanding the relationship between aging and dementia.
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DOI：
10.18632/aging.100838
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Schubert D
中科院分区：
文献类型：
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作者：
Currais A;Goldberg J;Farrokhi C;Chang M;Prior M;Dargusch R;Daugherty D;Armando A;Quehenberger O;Maher P;Schubert D
由于年龄是散发性阿尔茨海默病（AD）的最大风险因素，基于老年相关脑毒性的表型筛选被用于开发有效的神经营养药物J147。由于衰老的某些方面可能是AD的主要原因，我们假设J147对快速衰老的SAMP8小鼠中的AD相关病理学有效，并且可以用于鉴定衰老对AD的一些分子贡献。采用包容性和整合性多组学方法研究老年和年轻SAMP8小鼠的蛋白质和基因表达、代谢物水平和认知。J147减少了老年SAMP8小鼠的认知缺陷，同时恢复了与人类AD，血管病理学，突触功能受损和炎症相关的多种分子标志物，使其接近年轻表型。本研究中使用的广泛测定确定了与衰老相关的分子变化的子集，这可能是AD发展所必需的。
Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD-associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD. An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD.