A comprehensive multiomics approach toward understanding the relationship between aging and dementia

被引：67

作者：

Currais, Antonio ^{[1
]}

Goldberg, Joshua ^{[1
]}

Farrokhi, Catherine ^{[1
]}

Chang, Max ^{[1
]}

Prior, Marguerite ^{[1
]}

Dargusch, Richard ^{[1
]}

Daugherty, Daniel ^{[1
]}

Armando, Aaron ^{[2
]}

Quehenberger, Oswald ^{[2
]}

Maher, Pamela ^{[1
]}

Schubert, David ^{[1
]}

机构：

[1] Salk Inst Biol Studies, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

来源：

AGING-US | 2015年 / 7卷 / 11期

关键词：

aging; Alzheimer's disease; multiomics; SAMP8; mice; inflammation; J147; ALZHEIMERS-DISEASE; DOCOSAHEXAENOIC ACID; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE STRESS; GLUTAMATE LEVELS; TAU; PHOSPHORYLATION; MOUSE; PATHOLOGY; MODEL;

D O I：

10.18632/aging.100838

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：937 / 955

页数：19

共 49 条

[1] An integrated omics analysis of eicosanoid biology [J].