Long-Term Dietary Consumption of Grapes Alters Phenotypic Expression in Skeletal Muscle of Aged Male and Female Mice

(1) Background: Nutrigenomics investigates how diet influences gene expression and how genetic variation impacts dietary responses. Grapes, rich in phytochemicals, exhibit potential disease-preventive properties through nutrigenomic mechanisms rather than direct chemical interactions. This study aimed to explore the modulation of gene expression in muscle tissue resulting from long-term grape consumption. (2) Methods: A mouse model was employed to assess gene expression in the skeletal muscles of males and females fed a grape-enriched diet versus a bland diet over 2.5 years. Heatmaps and principal component analyses were performed to identify patterns, and pathway analyses using KEGG, GO, and Reactome were conducted. (3) Results: Significant sex-specific gene expression changes were observed, with female phenotypes showing greater alterations and converging toward male-like characteristics. Twenty-five differentially expressed genes associated with muscle health were identified. Up-regulated genes such as <i>Ahsg</i>, <i>Alb</i>, <i>Apoa1</i>, and <i>Arg1</i>, and down-regulated genes including <i>Camp</i>, <i>Lcn2</i>, and <i>Irf4</i>, suggest improved muscle function. (4) Conclusions: Long-term grape consumption appears to enhance female muscle traits toward a male-like phenotype, potentially indicating broader health benefits. Further studies and clinical trials are needed to confirm human applicability and the physiological implications of these findings. Nonetheless, this research underscores the role of nutrigenomics in understanding dietary influences on gene expression and sex-specific responses.