Further studies in a prenatal X-ray exposure-induced MDD model showed that resveratrol, by activating SIRT1, reverses the transcriptional repression of tryptophan hydroxylase (TPH) 2, restores 5-HT synthesis, downregulates aging-associated epigenetic markers (p16/p21), and upregulates BDNF, thereby alleviating depression-like symptoms (Zhang et al., 2025). This evidence concerns the gene SIRT1 and major depressive disorder.