International Journal of Clinical Drug Practice & Pharmacotherapy

Abstract

Aging is a complex, multifactorial process shaped by the interplay between genetic makeup and dynamic regulatory systems, with epigenetic and epitranscriptomic mechanisms playing a central role in integrating environmental, metabolic, and lifestyle influences across the lifespan. This review examines how these regulatory layers govern biological aging, lifespan, and healthspan, their modulation by environmental and nutritional factors, and their potential as therapeutic targets. With advancing age, alterations in DNA methylation, chromatin organization, histone post-translational modifications, and RNA chemical marks disrupt gene regulatory networks, driving genomic instability, chronic inflammation, and metabolic dysfunction that collectively impact lifespan and healthspan. Emerging evidence highlights the role of RNA modifications in fine-tuning cellular homeostasis and protein synthesis.

Nutritional interventions and microbiota-derived metabolites, such as short-chain fatty acids, modulate these processes through nutrient-sensing pathways and metabolic cofactors, underscoring their dynamic and potentially reversible nature. Advances in high-throughput and multi-omics technologies reveal substantial inter-individual variability in biological aging trajectories and lifespan outcomes. Together, these findings position epigenetic and epitranscriptomic alterations as key mediators linking environmental exposures to disease risk and longevity. Integrating longitudinal human studies with multi-omics and computational approaches will be critical to refine biological age estimation and develop precision strategies to extend lifespan and health span.