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. 2024 Jan 26;27(2):108999.
doi: 10.1016/j.isci.2024.108999. eCollection 2024 Feb 16.

Time-resolved map of serum metabolome profiling in D-galactose-induced aging rats with exercise intervention

Xue Li  1 , Changling Wei  1 , Yu Jin  1 , Jinmei Zhang  1 , Pei Zhong  2 , Deman Zhang  1 , Xiaohan Huang  1
Affiliations

Time-resolved map of serum metabolome profiling in D-galactose-induced aging rats with exercise intervention

Xue Li et al. iScience. .

Abstract

Exercise, an intervention with wide-ranging effects on the whole body, has been shown to delay aging. Due to aging and exercise as modulator of metabolism, a picture of how exercise delayed D-galactose (D-gal)-induced aging in a time-resolved manner was presented in this paper. The mapping of molecular changes in response to exercise has become increasingly accessible with the development of omics techniques. To explore the dynamic changes during exercise, the serum of rats and D-gal-induced aging rats before, during, and after exercise was analyzed by un_targeted metabolomics. The variation of metabolites was monitored to reveal the specific response to D-gal-induced senescence and exercise in multiple pathways, especially the basal amino acid metabolism, including glycine serine and threonine metabolism, cysteine and methionine metabolism, and tryptophan metabolism. The homeostasis was disturbed by D-gal and maintained by exercise. The paper was expected to provide a theoretical basis for the study of anti-aging exercise.

Keywords: Biological sciences; Metabolomics; Omics; Physiology.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Exercise alleviated the spatial learning and memory ability of rats damaged by D-gal, which were detected by MWM test (A), (B), and (C) were tested before exercise intervention. (D), (E), and (F) were tested after exercise intervention (n = 5, Data were represented as mean ± standard deviation and were analyzed by one-way ANOVA analysis of GraphPad Prism 9. ∗∗p < 0.01 and ∗p < 0.05 indicate significant difference compared with C group, respectively; #p < 0.05 indicates a significant difference compared with A group. The comparison of (A), (B), (D), and (E) was done with the average of data for the entire period during the navigation phase.(A) and (D) Escape latency of rats on 1st–6th days in the navigation phase (B) and (E) Escape latency distance of rats on 1st–6th days in the navigation phase (C) and (F) The times of crossing platform of rats on the 7th day in the spatial exploration phase. See also Figure S1.
Figure 2
Figure 2
Exercise and aging regulated the homeostasis of serum metabolites in rats (A) Venn diagram of metabolites with significant change compared the 63rd day with the 0th day. (B) PCA of C, A, and AE groups on the fourth 63rd day (confidence interval = 0.9). (C), (D), and (E) were the volcano plots metabolites in the positive ion model. (F), (G), and (H) were the volcano plots metabolites in the negative ion model. The horizontal dashed line represents the threshold for p value of 0.05, and the vertical dashed lines represent thresholds for ± 2-fold changes. Both the 63rd day and the 0th day of the three groups were analyzed using paired tests. See also Figure S2.
Figure 3
Figure 3
Cluster analysis reveals similar and different metabolites in aging and exercise (A), (B), and (C) were analysis of individual behavior and pattern of metabolite (positive). (A), (B), and (C) were C, A, and AE groups, respectively. See also Figure S3.
Figure 4
Figure 4
Analysis of individual behavior and cluster of metabolite (negative) (A), (B), and (C) were the C, A, and AE groups, respectively. See also Figure S4.
Figure 5
Figure 5
Changes in the pattern of core metabolites and the enrichment of metabolites changed in the pattern of the core (A) and (E) The changes in patterns and the cluster score of positive and negative metabolites compared C with A group, respectively. (B) and (F) The changes in patterns and the cluster score of positive and negative metabolites compared A with AE group, respectively (The different colors indicate the pattern of the metabolites over time. The “core” in the third column indicates the metabolites with membership score > 0.7.). (C) and (G) The enrichment of positive and negative metabolites changed in patterns and the cluster score compared C with A group, respectively. (D) and (H) The enrichment of positive and negative metabolites changed in patterns and the cluster score compared A with the AE group, respectively. See also Figure S5 and Table S1.
Figure 6
Figure 6
Metabolic pathways regulated by aging and exercise (A) The main class of metabolites. (B) The KEGG enrichment of metabolites with the same trend between groups C and AE and that was opposite to group A. (C) The metabolites of glycine serine and threonine metabolism. (D) Schematic representation of selected metabolism of glycine, serine, and threonine metabolism; cysteine and methionine metabolism; tryptophan metabolism; and vitamin B6 metabolism. (E) The metabolites of vitamin B6 metabolism. (F) The metabolites of tryptophan metabolism. (G) The metabolites of cysteine methionine metabolism (Data of (C), (E), (F), and (G) were represented as median ± interquartile range). See also Figures S6, S7 Tables S2 and S3.
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