Nutrigenomics explores the relationship between diet and gene expression, as well as how genetic variations affect dietary responses. The consumption of vegetables and fruits is associated with a reduction in disease risk. These health benefits are mainly due to the presence of phytochemicals. Grapes contain over 1,600 phytochemicals that influence health through various factors such as absorption, growth condition, and digestion.
Grape phytochemicals influence digestion, heart, cognition, and more. Grapes prevent various diseases through nutrigenomic pathways rather than direct chemical effects. The current study published in Foods Journal examined the effect of long-term grape consumption on skeletal muscle aging and sex-based nutrigenomics variations in mice models.
A subset of the parent study included 480 C57BL/6J mice (age = 4 weeks, male = 240, female = 240) were included. After reaching 1 year of age, mice were randomized into four groups, each consisting of 120 mice. Half of the mice continued with a standard diet (SD), whereas the remaining half had a grape-enriched diet. At 2.5 years of age, five mice were randomly chosen from SD male (SDM), SD with grape powder male (SDGM), SD female (SDF), and SD with grape powder female (SDGF) groups. RNA was extracted from the muscle samples of 4 groups. The gene expression was conducted using the principal component and heatmaps analysis, whereas the mechanism used the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO).
There was no statistically significant difference observed in the muscle/weight ratios for SDM compared to SDGM (0.013 ± 0.003 vs 0.014 ± 0.004) with a P value of 0.85. Also, non-significance was reported between SDF and SDGF (0.050 ± 0.071 and 0.046 ± 0.067) with a P value of 0.93. Additionally, no significant differences were observed for SDM vs SDF (P = 0.28) and SDGM vs SDGF (P = 0.32). Furthermore, no significant differences were found in histopathological examinations among the four groups.
In the comparison between SDM and SDGM, 21,200 genes were identified, with 193 genes up-regulated and 104 down-regulated. Similarly, 23,016 genes were observed, with 157 genes up-regulated and 419 down-regulated in between SDF and SDGF groups. In differential gene expression analysis, the comparison between SDM and SDGM resulted in a net difference of 4.7 units, while SDF versus SDGF showed a difference of 2.7 units, and the sum of these differences was 7.4 units. These variations were observed between SDGM and SDGF with a net difference of 1.4 units.
In the KEGG pathway, 20 mechanisms were identified in comparison to SDM with SDF groups, in which SDF was significantly enriched compared to SDM with an adjusted P value (Padj) of <0.05. Grape-diet animals also showed 20 pathways, of which five were the same as in SD animals.
In GO domain analysis (cellular component [CC], biological process [BP], molecular function [MF] domains), there was a significant difference found in muscle features (function and structure) between 3 domains between SDGF and SDF (up-regulated, Padj < 0.05) or SDGM and SDM (up- or down-regulated, Padj < 0.05) groups. SDGM animals exhibited non-significance in carbon and carbon-carbon lyase activities of the MF domain compared to SGDF animals.
Finally, 25 differential gene expressions were identified related to muscle health including up-regulated genes like alpha-2-Heremans–Schmid glycoprotein (Ahsg), albumin (Alb), apolipoprotein 1 (Apoa1), and arginase 1 (Arg1) and down-regulated genes like cathelicidin antimicrobial peptide (Camp), lipocalin 2 (Lcn2), and interferon regulatory factor 4 (Irf4). The increased apolipoprotein 4 (Apoa4), apolipoprotein B mRNA editing enzyme, catalytic peptide 3 (Apobec3), Camp, Calsyntenin 3b (Clstn3b), Irf4,  Lcn2, lactotransferrin (Ltf), neutrophilic granule protein (Ngp), neuronatin (Nnat), secretory leukocyte protease inhibitor (Slpi) genes were observed in grape-fed groups (SDGF, SDGM) compared to SD-fed groups (SDF, SDM).
In conclusion, long-term consumption of grapes leads to an increase in female muscle traits similar to male muscle, which suggests potential health benefits. Future research and clinical trials are necessary to confirm its physiological mechanism in humans. However, this animal study investigates the importance of nutrigenomics in understanding gene expression and sex-based differences in aging.
Reference: Dave A, Park E-J, Piya S, Pezzuto JM. Long-Term Dietary Consumption of Grapes Alters Phenotypic Expression in Skeletal Muscle of Aged Male and Female Mice. Foods. 2025; 14(4):695. https://doi.org/10.3390/foods14040695
