The Power of Environment: A Comprehensive Review of the Exposome’s Role in Healthy Aging, Longevity, and Preventive Medicine—Lessons from Blue Zones and Cilento

Aging and longevity are shaped by the exposome, a dynamic network of environmental, social, and biological factors. Understanding how these exposures interact with biological mechanisms can inform strategies for healthier aging. Background/Objectives: This review explores the exposome as a dynamic system encompassing both protective and risk factors, with a specific focus on how beneficial environmental exposures, microbiome diversity, lifestyle behaviors, and resilience mechanisms contribute to successful aging. By analyzing high-longevity populations, such as the Blue Zones and Cilento, it aims to identify common determinants of successful aging. Methods: A mixed-method study was conducted, combining a systematic review of the English literature (2003-2024) with a comparative analysis of longevity regions. A structured search was performed in PubMed, Scopus, and Google Scholar using keywords such as "longevity", "Blue Zones", "Cilento", "microbiome", "environmental factors", and related terms. Additionally, qualitative and quantitative analysis were applied to assess key protective factors across different aging models. Results: This study identified key factors contributing to successful aging in longevity hotspots, including sustained exposure to biodiverse natural environments, adherence to Mediterranean or plant-based diet rich in polyphenols and probiotics, regular physical activity, strong social networks, and psychological resilience. A novel aspect of this review is the role of the gut microbiome as a mediator between environmental exposures and immune-metabolic health, influencing inflammation modulation and cellular aging. Despite geographic and cultural differences, case studies reveal a shared pattern of protective factors that collectively enhance lifespan and healthspan. Conclusions: The exposome is a critical determinant of aging trajectories, acting through complex interactions between environmental and biological mechanisms. By integrating insights from high-longevity populations, this mixed-method study proposes a comprehensive framework for optimizing microbiome health, enhancing resilience, and promoting protective environmental exposures. These findings provide a translational perspective to guide future interventions in aging research and global health initiatives.