Exploring NAD+ Dynamics and Interventions in Aging and Age-related Pathology

Nicotinamide adenine dinucleotide (NAD+) is a pivotal molecule in biochemistry and cellular physiology, renowned for its dual roles as a redox cofactor and a substrate for a range of signaling enzymes. Over recent years, research has highlighted the pervasive decline of NAD+ levels across multiple tissues as a hallmark of aging, intricately linking this depletion to the development and progression of age-related diseases. Key proteins such as sirtuins, poly(ADP-ribose) polymerases, and cyclic ADP-ribose synthases depend on NAD+ for their regulatory functions in DNA repair, chromatin remodeling, metabolic homeostasis, and the control of cellular senescence. Despite significant advances, central questions remain as to the mechanisms underlying NAD+ decline, its direct and indirect roles in driving the hallmarks of aging, and the bidirectional relationship between NAD+ dynamics and systemic health over time.Recent studies have strengthened the causal association between decreasing NAD+ concentrations and age-associated conditions including neurodegenerative disorders, sarcopenia, and insulin resistance. Experimental evidence indicates that restoring NAD+ levels through dietary or pharmacological interventions may mitigate certain aspects of biological aging and attenuate the progression of chronic disease. Nonetheless, the field still faces substantial gaps in translating these findings into clinically effective strategies, as the diversity of NAD+ repletion approaches, variability in disease outcomes, and long-term safety profiles remain incompletely defined. There is an ongoing debate regarding the best biomarkers of NAD+ status, its systemic versus tissue-specific effects, and optimal intervention windows.This Research Topic aims to advance our understanding of NAD+ biology in aging by assembling cutting-edge research and balanced perspectives on its functional roles, the mechanistic basis of its decline, and the emerging therapeutic landscape targeting NAD+ metabolism. By drawing together foundational, translational, and clinical studies, the goal is to clarify the multifaceted relevance of NAD+ in aging processes and to guide future discovery toward practical interventions for age-related diseases.The scope of this Research Topic encompasses mechanistic, preclinical, and clinical investigations into NAD+ in aging and age-related disease, while excluding unrelated aspects of metabolism and aging unrelated to NAD+-dependent pathways. To gather further insights into this rapidly evolving area, we welcome articles addressing, but not limited to, the following themes:o Mechanistic drivers of NAD+ decline during aging and their interplay with hallmarks of agingo Role of NAD+ metabolism in age-related pathologieso Strategies and therapeutic agents to modulate NAD+ levelso Preclinical and clinical evaluation of NAD+ repletion therapieso Biomarker development and assessment of NAD+ status in health and diseaseo Regulatory and safety considerations for NAD+-targeted therapiesWe welcome a range of article types, including original research, reviews, perspectives, and clinical studies. Topic editors: Jonas Thue Treebak, Rubén Zapata-Pérez, Ruben Rabadan Ros Source: https://www.frontiersin.org/research-topics/79108/exploring-nad-dynamics-and-interventions-in-aging-and-age-related-pathology