NAD+ in Aging: Molecular Mechanisms and Translational Implications
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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NAD+ in Aging : Molecular Mechanisms and Translational Implications. / Fang, Evandro F.; Lautrup, Sofie; Hou, Yujun; Demarest, Tyler G.; Croteau, Deborah L.; Mattson, Mark P.; Bohr, Vilhelm A.
I: Trends in Molecular Medicine, Bind 23, Nr. 10, 2017, s. 899-916.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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TY - JOUR
T1 - NAD+ in Aging
T2 - Molecular Mechanisms and Translational Implications
AU - Fang, Evandro F.
AU - Lautrup, Sofie
AU - Hou, Yujun
AU - Demarest, Tyler G.
AU - Croteau, Deborah L.
AU - Mattson, Mark P.
AU - Bohr, Vilhelm A.
PY - 2017
Y1 - 2017
N2 - 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. 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.
AB - 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. 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.
KW - aging
KW - autophagy
KW - clinical application
KW - DNA repair
KW - metabolism
KW - mitophagy
KW - NAD
KW - neurodegenerative disorder
KW - stem cell
U2 - 10.1016/j.molmed.2017.08.001
DO - 10.1016/j.molmed.2017.08.001
M3 - Review
C2 - 28899755
AN - SCOPUS:85028926903
VL - 23
SP - 899
EP - 916
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
SN - 1471-4914
IS - 10
ER -
ID: 184772429