As the brain ages, it undergoes significant cellular changes that reflect compromised bioenergetics, impaired neuroplasticity, reduced resilience and aberrant neuronal network activity, and increased inflammation. These alterations render the aging brain more vulnerable to neurodegenerative diseases, including Alzheimer's diseases, vascular dementia, and stroke. Recent research has illuminated how sedentary and overindulgent lifestyles accelerate brain aging, while intermittent bioenergetic challenges promote healthier aging. Intermittent fasting (IF), a dietary regimen that alternates between periods of unrestricted food intake and fasting without compromising nutritional quality, has been extensively studied in animal models. Prophylactic IF has shown promise in mitigating the development of age-related dementia and protecting against stroke. Despite substantial experimental evidence supporting the benefits of IF for age-related brain diseases, our understanding of the underlying molecular and cellular mechanisms remains limited. Here, we demonstrate that IF induces significant changes in chromatin accessibility, the epigenetic landscape, gene expression, and the proteome, which in turn affect key biological pathways. Through comprehensive analysis, we identify novel regulatory mechanisms activated by IF. Integrative analyses reveal a strong correlation between epigenetic changes, chromatin accessibility, gene expression, and the proteomic landscape in response to IF. We also pinpoint several key transcription factors that are associated with the beneficial effects of IF. Our results provide new insights into how IF-induced changes in chromatin dynamics influence gene expression, offering a mechanistic understanding of its health benefits. This study not only advances our understanding of dietary restriction but also opens new avenues for exploring IF as a therapeutic strategy for age-related diseases.