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Proper NAD levels are necessary to sustain circadian rhythms. But the opposite also appears true, that disrupting circadian rhythms also disrupts NAD levels.


Here are the studies:

Mar 30, 2023

Circadian Rhythm

Proceedings of the National Academy of Sciences

NAMPT-dependent NAD+ biosynthesis controls circadian metabolism in a tissue-specific manner

Basse, Astrid L.


Here, we show that NAMPT-dependent control over the molecular clock varies substantially between tissues...our findings reveal that peripheral molecular clocks and metabolic biorhythms are shaped in a highly tissue-specific manner by NAMPT-dependent NAD+ synthesis.

Mar 27, 2023

Circadian Rhythm

Nature Communications

Time-of-day defines NAD+ efficacy to treat diet-induced metabolic disease by synchronizing the hepatic clock in mice

Escalante-Covarrubias, Quetzalcoatl


Here, we demonstrate that time-of-day determines the efficacy of NAD+ treatment for diet-induced metabolic disease in mice. Increasing NAD+ prior to the active phase in obese male mice ameliorated metabolic markers including body weight, glucose and insulin tolerance, hepatic inflammation and nutrient sensing pathways. However, raising NAD+ immediately before the rest phase selectively compromised these responses....In humans, clinical trials aiming to boost endogenous NAD+ for treatment of metabolic diseases are increasing, showing promising results... However, all these studies mostly overlook the time of drug intake, which is selected based on practicalities or attempting to displace side effects from the patient’s active phase. Considering our results, we propose that time of treatment dictates the amplitude of metabolic benefits from rising NAD+ levels, which ideally outlines the basic strategy of chronobiology-based NAD+ therapy.

Oct 11, 2022

Circadian Rhythm - Aging - Heart

American Journal of Physiology - Cell Physiology

Circadian cardiac NAD+ metabolism, from transcriptional regulation to healthy aging

Carpenter, Bryce J.


...Recent studies have expanded on the role of circadian rhythms and the core clock factors that maintain them in the regulation of NAD+ levels in the heart. This has revealed that NAD+ pools and their use are tightly linked to cardiac function, but also heart failure. The convergence of these fields, namely, clock regulation, heart disease, and NAD+ metabolism present a complex network ripe with potential scientific and clinical discoveries, given the growing number of animal models, recently developed technology, and opportunity for safe and accessible precursor supplementation...

Aug 15, 2022

Circadian Rhythm - Metabolism


Time-of-day defines the efficacy of NAD+ to treat diet-induced metabolic disease by adjusting oscillations of the hepatic circadian clock

Escalante-Covarrubias, Q


The circadian clock is a time-tracking endogenous system which anticipates and coordinates adaptation to daily environmental fluctuations. Circadian misalignment leads to obesity, which is accompanied by reduced levels of the clock-controlled metabolite NAD+. Concomitantly, increasing NAD+ levels is emerging as a therapy for diet-induced obesity and type 2 diabetes; however, the impact of daily fluctuations of NAD+ on these therapies remains unknown. Here, we demonstrate that time-of-day determines the efficacy of NAD+ as a therapy for diet-induced metabolic disease in mice...

Jun 1, 2022

Circadian Rhythm

Seminars and Cell and Development Biology

Circadian NAD(P)(H) cycles in cell metabolism

Levine, Daniel


In this review, we focus on the role of the nucleotide NAD(P)(H) and NAD+-dependent sirtuin deacetylases as integrators of circadian and metabolic cycles, as well as the implications for this interrelationship in healthful aging.

May 9, 2022

Heart - Vascular - Circadian Rhythm - Aging

Frontiers in Molecular Medicine

Nicotinamide Riboside Improves Cardiac Function and Prolongs Survival After Disruption of the Cardiomyocyte Clock

Dierickx, Pieterjan


Here, we show that supplementation with the NAD+ precursor NR as a dietary supplement improves heart function and extends the lifespan of female mice lacking cardiac REV-ERBs. Thus, boosting NAD+ levels can improve cardiac function in a setting of heart failure caused by disruption of circadian clock factors, providing new insights into the links between the circadian clock, energy metabolism, and cardiac function.

Jun 4, 2020

Circadian Rhythm

Molecular Cell

NAD+ Controls Circadian Reprogramming through PER2 Nuclear Translocation to Counter Aging

Levine, Daniel


Disrupted sleep-wake and molecular circadian rhythms are a feature of aging associated with metabolic disease and reduced levels of NAD+, yet whether changes in nucleotide metabolism control circadian behavioral and genomic rhythms remains unknown. Here, we reveal that supplementation with the NAD+ precursor nicotinamide riboside (NR) markedly reprograms metabolic and stress-response pathways that decline with aging through inhibition of the clock repressor PER2. NR enhances BMAL1 chromatin binding genome-wide through PER2K680 deacetylation, which in turn primes PER2 phosphorylation within a domain that controls nuclear transport and stability and that is mutated in human advanced sleep phase syndrome. In old mice, dampened BMAL1 chromatin binding, transcriptional oscillations, mitochondrial respiration rhythms, and late evening activity are restored by NAD+ repletion to youthful levels with NR. These results reveal effects of NAD+ on metabolism and the circadian system with aging through the spatiotemporal control of the molecular clock.

Aug 10, 2017

Circadian Rhythm - Aging - Liver


Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging

Sato, Shogo


Our findings reveal that aging operates by reprogramming the circadian transcriptome. We show that these age-dependent changes in circadian gene expression occur in a highly tissue-specific manner, as demonstrated by a comparative analysis of the liver transcriptional landscape versus epidermal and skeletal muscle stem cells...Remarkable circadian changes take place during aging and calorie restriction in the liver...This oscillatory acetylation signature is drastically dampened in old mice whereas calorie restriction serves to rescue the age-dependent loss of global protein acetylation. These changes in protein acetylation are likely due to improved NAD+ availability, enhanced SIRT1 activity, and increased levels of acetate and acetyl-coA ...Our results centrally place the circadian NAD+ salvage pathway in mediating the beneficial effects of calorie restriction ...

Oct 8, 2015

Circadian Rhythm


Shifting eating to the circadian rest phase misaligns the peripheral clocks with the master SCN clock and leads to a metabolic syndrome

Mukherji, Atish


The light-entrained master central circadian clock (CC) located in the suprachiasmatic nucleus (SCN) not only controls the diurnal alternance of the active phase (the light period of the human light-dark cycle, but the mouse dark period) and the rest phase (the human dark period, but the mouse light period), but also synchronizes the ubiquitous peripheral CCs (PCCs) with these phases to maintain homeostasis. We recently elucidated in mice the molecular signals through which metabolic alterations induced on an unusual feeding schedule, taking place during the rest phase [i.e., restricted feeding (RF)], creates a 12-h PCC shift. Importantly, a previous study showed that the SCN CC is unaltered during RF, which creates a misalignment between the RF-shifted PCCs and the SCN CC-controlled phases of activity and rest. However, the molecular basis of SCN CC insensitivity to RF and its possible pathological consequences are mostly unknown. Here we deciphered, at the molecular level, how RF creates this misalignment. We demonstrate that the PPARα and glucagon receptors, the two instrumental transducers in the RF-induced shift of PCCs, are not expressed in the SCN, thereby preventing on RF a shift of the master SCN CC and creating the misalignment. Most importantly, this RF-induced misalignment leads to a misexpression (with respect to their normal physiological phase of expression) of numerous CC-controlled homeostatic genes, which in the long term generates in RF mice a number of metabolic pathologies including diabetes, obesity, and metabolic syndrome, which have been reported in humans engaged in shift work schedules.

NAD Research - Circadian

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