Mevalonate increased the lifespan and alleviated aging-related phenomena in C. elegans. (A) Schematic of mevalonate in C. elegans. (B) Lifespan analysis of N2 and mevalonate (0.5 M, 1 M, 2 M, and 5 M). Lifespan was calculated using the log-rank (Kaplan–Meier) method. (C) Mean lifespan of Fig. 6B (n = 4 biological replicates). (D) Fluorescence of lipofuscin (scale bar, 100 μm). Lipofuscin accumulation was measured by blue excitation light (from left to right are N2, 0.5 M, 1 M, 2 M, and 5 M of mevalonate). (E) Pharyngeal pumping assay (n = 10/groups for 3 biological replicates). (F) Body bending assay (n = 10/groups for 3 biological replicates). (G) Lipofuscin accumulation assay (n = 3 biological replicates). Statistical comparisons were performed t-test (Fig. 6C, 6E, 6F and 6G). P-values of < 0.05, < 0.01, and < 0.001 are represented by *, **, and ***, respectively. ns indicates not significant in t-test. (H) Volcano plot of gene expression profiles after mevalonate administration. Up-regulated and down-regulated genes (|log2FC| > 0.58 and FDR < 0.05) are colored red and blue, respectively. (I) Gene set enrichment analysis (GSEA) after mevalonate administration. Top 15 up-regulated and down-regulated enrichment pathways are shown. (J) Enrichment plot of FATTY_ACID_METABOLISM in KEGG database. (K) Heatmap of gene expression of significantly changed genes in fatty acid metabolism.
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