RECENT UNDERSTANDING OF EPIGENETIC AGING, REJUVENATION, AND LONGEVITY PRINCIPLES FOR REVERSE AGING

Abstract

Aging is an intricate biological phenomenon driven by the progressive erosion of epigenetic landscapes, manifesting as widespread DNA methylation drift, histone modification imbalances, and large-scale chromatin reorganization. These molecular alterations collectively compromise gene regulatory networks and precipitate cellular functional decline. This review synthesizes contemporary evidence on how epigenetic dysregulation orchestrates aging and age-associated neurodegenerative conditions, evaluates the diagnostic utility of epigenetic clock technologies spanning four generations, and examines the mechanistic basis of cellular reprogramming using Yamanaka factors (OSKM) as a strategy for partial epigenetic age reversal. Key Interventions Covered: Therapeutic strategies reviewed include CRISPR-based epigenome editing, senolytic pharmacology, NAD⁺ supplementation, sirtuin modulation, mTOR pathway inhibition, and AMPK activation. Epigenetic modifications are fundamentally reversible, positioning the epigenome as a therapeutically actionable substrate for anti-aging interventions. Converging advances in precision genome editing, artificial intelligence, and multi-omics profiling are establishing a scientific foundation for extending human healthspan.