Over the past few decades, the global average life expectancy has considerably increased, reaching approximately 60 years. Recent estimates predict that by 2050, the number of individuals aged 60 and above will double compared to the present population [1]. Age is a progressive accumulation of irreversible cellular and molecular damage, including free radicals, significantly resulting in various age-associated diseases [2]. In different organisms, the changes in diet are related to the decrease in the production of free radicals and can extend the lifespan [3]. The composition of a person's gut microbiota is influenced throughout their life by a combination of factors such as diet, physical activity, work activity, socio-economic status, and other environmental elements. These factors collectively shape the individual's intestinal microbiota, which undergoes changes corresponding to age and individual characteristics [4,5]. Dietary restriction has been shown to extend lifespan and postpone the onset of age-related diseases, possibly by controlling epigenetic changes [6]. Further examination has been dedicated to exploring potential epigenetic mechanisms that could explain the benefits of dietary restriction and dietary therapies. This review article delves into the potential role of polyphenols, a group of bioactive compounds in various plant-based diets, in influencing cellular and molecular pathways associated with aging and disease. The article suggests that polyphenols could serve as intermediaries for the observed effects of dietary restriction and dietary interventions [7]. Earlier studies demonstrated that taking omega-3 supplements caused changes in DNA methylation patterns at multiple gene sites, including some involved with inflammation and glucose metabolism [8]. Despite the promising outcomes, numerous uncertainties remain regarding the optimal types, dosages, and timing of dietary restriction and interventions for inducing epigenetic modifications. Furthermore, it remains unclear whether specific nutritional interventions may produce varying effects based on factors such as age, sex, or genetic characteristics of individuals [9]. Furthermore, by utilizing systems biology and computational methodologies, combined with acknowledging the influence of gut microbiota, researchers have gained significant knowledge to create effective dietary interventions [10]. To enhance the benefits of calorie restriction and intermittent fasting, scientists have started utilizing systems biology and computational techniques. Using system biology researchers can explore interconnected networks of genes, proteins, and metabolites in complex biological systems, facilitating a comprehensive comprehension of the effects of dietary interventions on various physiological processes [11]. Through computational modelling and analysis of these interconnected systems, researchers can gain valuable knowledge about the underlying mechanisms of calorie restriction and intermittent fasting, aiding in identifying crucial molecular targets and pathways implicated in these effects [12]. Studies have provided valuable insights into the significant involvement of gut microbiota in modulating the impacts of dietary interventions on human well-being, which in turn impacts metabolic health and the way the host responds to nutritional interventions [13].