Yundong Peng, Rui Li, Huan Li, Jun Zhou, Xuanshi Liu, Guilherme Targino Valente, Tatiana de Campos Melo, Sifan Chen, Lei Gu
ABSTRACT Aging is orchestrated by interconnected hallmarks such as genomic instability, mitochondrial dysfunction, cellular senescence, and disrupted intercellular communication, which collectively drive chronic disease progression. Recent advances have expanded therapeutic opportunities to include pharmacological agents, gene and epigenome editing, stem cell based interventions, microbiome modulation, and nanomedicine. Artificial intelligence and multi‐omics integration are further accelerating target discovery and patient stratification. This review synthesizes these modalities within a unified framework that explicitly links hallmarks to biomarkers and therapeutic strategies, critically evaluates preclinical versus clinical outcomes, and examines why promising interventions often fail to translate. We propose an integrative model emphasizing biomarker alignment, phenotype stratification, and regulatory adaptation. By embedding mechanistic insights into clinically predictive and patient‐centered designs, this review outlines a roadmap for advancing gerotherapeutics to extend healthspan.