Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants

被引:105
作者
Park, Sang-Kyu [1 ]
Kim, Kyoungmi [2 ,3 ]
Page, Grier P. [2 ,3 ]
Allison, David B. [2 ,3 ]
Weindruch, Richard [4 ,5 ]
Prolla, Tomas A. [1 ]
机构
[1] Univ Wisconsin, Dept Genet & Med Genet, Madison, WI 53706 USA
[2] Univ Alabama Birmingham, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA
[3] Univ Alabama Birmingham, Clin Nutr Res Ctr, Birmingham, AL 35294 USA
[4] Univ Wisconsin, Vet Adm Hosp, Dept Med, Madison, WI 53706 USA
[5] Univ Wisconsin, Vet Adm Hosp, Wisconsin Primate Res Ctr, Madison, WI 53706 USA
来源
AGING CELL | 2009年 / 8卷 / 04期
关键词
aging; antioxidants; biomarkers; caloric restriction; microarray; mouse; ACETYL-L-CARNITINE; CALORIC RESTRICTION; IN-VIVO; COMPLEMENT ACTIVATION; CATHEPSIN-S; MATRIX METALLOPROTEINASE-2; ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; ACIDIC PROTEIN; SKAP-HOM;
D O I
10.1111/j.1474-9726.2009.00496.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
P>We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5 month) and old (25 month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H and B6C3F(1)). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein and cathepsin S. Caloric restriction (CR) inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl-l-carnitine and tempol were as effective as CR in the heart, and alpha-lipoic acid and coenzyme Q(10) were as effective as CR in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis.
引用
收藏
页码:484 / 495
页数:12
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