Non-Human Primates as a Comprehensive Model for Studying Epigenetic Markers of Aging

Non-human primates (NHPs) serve as indispensable models for aging research due to their evolutionary proximity to humans, conserved epigenetic mechanisms, and lifespans amenable to longitudinal investigation. This review synthesizes age-related epigenetic modifications in NHPs, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulation, and evaluates their alignment with human epigenetic markers. Epigenetic clocks developed on human data demonstrate robust predictive capacity in NHPs, and numerous age-associated methylation patterns are evolutionarily conserved. However, most epigenetic changes exhibit pronounced tissue specificity, with only a limited number of markers showing cross-tissue and cross-species consistency. Critical modulating factors such as sexual dimorphism, social hierarchy, environmental stressors, and early-life adversity significantly influence epigenetic aging trajectories. Current research remains restricted to a narrow subset of NHP taxa, predominantly macaques and baboons; expanding to include great apes would deepen our understanding of primate epigenetic aging. Advancing the field requires integrating multi-tissue, multi-species, and multi-omics approaches, including single-cell resolution analyses, to distinguish conserved mechanisms from lineage-specific adaptations. Such an integrative framework is essential for translating epigenetic discoveries into clinical interventions. By leveraging the unique advantages of NHPs, controlled interventional studies, longitudinal multi-tissue sampling, and causal mechanistic dissection, researchers can bridge basic discovery and therapeutic development. This approach promises to refine our understanding of aging biology and guide the rational design of next-generation therapeutics, from epigenetic modulators to lifestyle interventions, ultimately paving the way for personalized strategies that extend both lifespan and healthspan.