title: A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.
abstract: Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.
authors.affiliation: Computational Modeling Sciences, Platform Technologies and Science, GlaxoSmithKline Research & Development, Shanghai, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Meng
authors.affiliation: Neurodegeneration DPU, GlaxoSmithKline Research & Development, Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Computational Modeling Sciences, Platform Technologies and Science, GlaxoSmithKline Research & Development, Shanghai, China.
authors.forename: Hongkang
authors.initials: H
authors.lastname: Mei
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C506096:DEPP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C493729:Runx3 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human