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. 2009 Aug;8(4):484-95.
doi: 10.1111/j.1474-9726.2009.00496.x. Epub 2009 Jun 25.

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

Sang-Kyu Park  1 , Kyoungmi Kim, Grier P Page, David B Allison, Richard Weindruch, Tomas A Prolla
Affiliations

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

Sang-Kyu Park et al. Aging Cell. 2009 Aug.

Abstract

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.

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Figures

Fig. 1
Fig. 1
Time-course quantitative RT-PCR of biomarkers of heart aging in B6 mice. The effect of aging and CR on the expression of selected biomarkers of heart aging is measued. Relative amount of mRNA compared to young control is shown for each sample. (A) C4, (B) Csprs, (C) Pah, (D) Cxcl14; (E) Scap2. C5, 5-month-old control grouop. Lines above/below bars indicate standard error.
Fig. 2
Fig. 2
Time-course quantitative RT-PCR of biomarkers of cerebellum aging in B6 mice. The effect of aging and CR on the expression of selected biomarkers of cerebellum aging is measued. Relative amount of mRNA compared to young control is shown for each sample. (A) C4, (B) C1qa, (C) Ctss, (D) Lzp-s, (E) Gfap. C5, 5-month-old control grouop. Lines above/below bars indicate standard error.
Fig. 3
Fig. 3
Common pathways of heart aging in multiple mouse strains. Parametric analysis of gene set enrichment (PAGE) identified gene sets significantly enriched (P < 0.05) in heart aging among at least 6 strains out of 7 tested. Each row corresponds to the transcriptional alteration of each gene set with aging. Gene sets up-regulated with aging are shown in red, while gene sets down-regulated with aging are shown in blue. Labels indicate the GO numbers and GO term of each pathway.
Fig. 4
Fig. 4
Common pathways of cerebellum aging in multiple mouse strains. Parametric analysis of gene set enrichment (PAGE) identified gene sets significantly enriched (P < 0.05) in cerebellum aging among at least 5 strains out of 6 tested. Each row corresponds to the transcriptional alteration of each gene set with aging. Gene sets up-regulated with aging are shown in red, while gene sets down-regulated with aging are shown in blue. Labels indicate the GO numbers and GO term of each pathway.
Fig. 5
Fig. 5
The effect of middle age-onset CR and antioxidant supplementation on the expression of biomarkers of heart aging. Relative amount of mRNA compared to young control is shown for each group. (A) C4, (B) Csprs, (C) Pah, (D) Cxcl14, (E) Scap2. C5, 5-month-old control; C30, 30-month-old control; CR, caloric restriction; LA, α-lipoic acid; CQ, coenzyme Q10; RE, resveratrol; CU, curcumin; LY, lycopene; AC, acetyl-L-carnitine; AS, astaxanthin; TP, tempol. Lines above/below bars indicate standard error. The one-way ANOVA test showed significant p-value (P < 0.01) in all genes tested. * Significantly different from C30 (P < 0.05).
Fig. 6
Fig. 6
The effect of middle age-onset CR and antioxidant supplementation on the expression of biomarkers of cerebellum aging. Relative amount of mRNA compared to young control is shown for each group. (A) C4, (B) C1qa, (C) Ctss, (D) Lzp-s, (E) Gfap. C5, 5-month-old control; C30, 30-month-old control; CR, caloric restriction; LA, α-lipoic acid; CQ, coenzyme Q10; RE, resveratrol; CU, curcumin; LY, lycopene; AC, acetyl-L-carnitine; AS, astaxanthin; TP, tempol. Lines above/below bars indicate standard error. The one-way ANOVA test showed significant p-value (P < 0.01) in all genes tested. * Significantly different from C30 (P < 0.05).
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