Interplay between aging and metabolic diseases: from molecular mechanisms to therapeutic horizons

Aging and metabolic diseases are intricately linked through bidirectional molecular mechanisms that foster a harmful cycle of physiological decline. This cycle is driven by several key factors, including altered nutrient sensing, mitochondrial dysfunction, cellular senescence, chronic inflammation, epigenetic modifications, circadian rhythm disruptions, and imbalances in the gut microbiota. Emerging interventions targeting this aging-metabolism axis hold significant promise for extending healthspan. These approaches include the use of pharmacological mimetics, senolytics, multi-omics strategies, and microbiome modulation, all of which aim to restore metabolic homeostasis and mitigate age-related pathologies. However, several challenges remain in translating these strategies into clinical practice. These include the need for tissue-specific targeting, ensuring the long-term safety of interventions, and addressing socioeconomic disparities in healthcare access. Future research efforts are focusing on integrating multi-omic technologies, organoid and human cellular models, and developing equitable precision medicine frameworks. These initiatives aim to extend healthspan and reduce the global impact of aging-related metabolic diseases.