NAD+ in Aging: Molecular Mechanisms and Translational Implications. Issue 10 (October 2017)

• Record Type: Journal Article
• Authors: Fang, Evandro F.; Lautrup, Sofie; Hou, Yujun; Demarest, Tyler G.; Croteau, Deborah L.; Mattson, Mark P.; Bohr, Vilhelm A.
• Is Part Of: Trends in molecular medicine. Volume 23:Issue 10(2017)
• Page Start: 899
• Page End: 916
• Publication Date: 2017-10
• Subjects: NAD+ -- metabolism -- autophagy -- neurodegenerative disorder -- mitophagy -- aging -- stem cell -- DNA repair -- clinical application; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2017.08.001
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : The coenzyme NAD + is critical in cellular bioenergetics and adaptive stress responses. Its depletion has emerged as a fundamental feature of aging that may predispose to a wide range of chronic diseases. Maintenance of NAD + levels is important for cells with high energy demands and for proficient neuronal function. NAD + depletion is detected in major neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, cardiovascular disease and muscle atrophy. Emerging evidence suggests that NAD + decrements occur in various tissues during aging, and that physiological and pharmacological interventions bolstering cellular NAD + levels might retard aspects of aging and forestall some age-related diseases. Here, we discuss aspects of NAD + biosynthesis, together with putative mechanisms of NAD + action against aging, including recent preclinical and clinical trials. Trends: Recent discoveries have demonstrated an age-dependent decrease in cellular and/or tissue NAD + levels in laboratory animal models. Moreover, NAD + depletion has been linked to multiple hallmarks of aging. In premature aging animal models, NAD + levels are decreased, while NAD + replenishment can improve lifespan and healthspan through DNA repair and mitochondrial maintenance. Mitochondrial autophagy (mitophagy) has a major role in clearance of damaged and/or dysfunctional mitochondria, and compromised mitophagy has been linked to metabolic disorders, neurodegeneration [including Alzheimer's disease (AD) and Parkinson's disease (PD)] in addition to aging, and other age-related diseases. New evidence suggests that NAD + precursors, such as nicotinamide and nicotinamide riboside, forestall pathology and cognitive decline in mouse models of AD. NAD + supplementation can inhibit multiple aging features in animal models. This highlights essential roles for NAD + in maintaining healthy aging, and suggests that NAD + repletion may have broad benefits in humans.