Age-Dependent Decline of NAD+—Universal Truth or Confounded Consensus?

Peluso, Augusto; Damgaard, Mads V.; Mori, Marcelo A.; Treebak, Jonas T.

doi:10.3390/nu14010101

Cited by 22 publications

(14 citation statements)

References 103 publications

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“…Thus, to the best of our knowledge, declines in the blood levels of NAD + in the neurological and cardiological patients, shown in our work ( Figure 1 and Supplementary Figure 2 ), have not been demonstrated before, although decreased NAD levels are known in healthy aging ( 16 – 18 ). Our data support this finding, as we also observe a slight decline in the blood NAD + content in healthy subjects with age ( Supplementary Figure 3 ).…”

Section: Discussionsupporting

confidence: 42%

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Efficient Assay and Marker Significance of NAD+ in Human Blood

et al. 2022

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Oxidized nicotinamide adenine dinucleotide (NAD+) is a biological molecule of systemic importance. Essential role of NAD+ in cellular metabolism relies on the substrate action in various redox reactions and cellular signaling. This work introduces an efficient enzymatic assay of NAD+ content in human blood using recombinant formate dehydrogenase (FDH, EC 1.2.1.2), and demonstrates its diagnostic potential, comparing NAD+ content in the whole blood of control subjects and patients with cardiac or neurological pathologies. In the control group (n = 22, 25–70 years old), our quantification of the blood concentration of NAD+ (18 μM, minimum 15, max 23) corresponds well to NAD+ quantifications reported in literature. In patients with demyelinating neurological diseases (n = 10, 18–55 years old), the NAD+ levels significantly (p < 0.0001) decrease (to 14 μM, min 13, max 16), compared to the control group. In cardiac patients with the heart failure of stage II and III according to the New York Heart Association (NYHA) functional classification (n = 24, 42–83 years old), the blood levels of NAD+ (13 μM, min 9, max 18) are lower than those in the control subjects (p < 0.0001) or neurological patients (p = 0.1). A better discrimination of the cardiac and neurological patients is achieved when the ratios of NAD+ to the blood creatinine levels, mean corpuscular volume or potassium ions are compared. The proposed NAD+ assay provides an easy and robust tool for clinical analyses of an important metabolic indicator in the human blood.

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Section: Discussionsupporting

confidence: 42%

“…The correlation between the concentrations of NAD + in blood/plasma and tissues has been studied in aging ( 16 – 18 ). The reduction in NAD + level with age is observed in healthy human brain ( 19 , 20 ), liver ( 21 ), red blood cells ( 22 ) and macrophages ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Efficient Assay and Marker Significance of NAD+ in Human Blood

et al. 2022

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“…This might partly explain the failure to observe a significant association between NAD + contents and aging in other male age groups. In addition, the association of NAD + with aging might varied across organs and tissues ( 28 ). We only tested the NAD + level in whole blood samples so that it could reflect the association of aging and NAD + contents in human whole blood.…”

Section: Discussionmentioning

confidence: 99%

Association of Human Whole Blood NAD+ Contents With Aging

Yang

Luo

et al. 2022

Front. Endocrinol.

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BackgroundNAD+, nicotinamide adenine dinucleotide, is mostly described to associate with the aging process. We aimed to investigate the association between human whole blood NAD+ contents and aging in a relative large-scale community-based population and further to address the gender impact on this association.MethodsWe recruited 1,518 participants aged over 18 years old and free of cardiovascular and any type of cancer from the Jidong community from 2019 to 2020. Whole blood NAD+ level was measured by cycling assay and LC-mass spectroscopy assay. The chronological age and clinical data were collected using standard questionnaires. The participants were divided into five groups according to their chronological age. General liner regression model was performed to analyze the association between NAD+ contents and aging. In addition, we also conducted subgroup analysis by gender.ResultsThe mean age of included 1,518 participants was 43.0 years, and 52.6% of them were men. The average levels of whole blood NAD+ of total participants was 33.0 ± 5.5 μmol/L. The whole blood NAD+ contents in men were significantly higher than that in women (34.5 vs. 31.3 μmol/L). There was significant difference in the meat diet among NAD+ quartile groups (p = 0.01). We observed a decline trend of NAD+ contents with aging before 50 years in total participants with significant level in 40–49 years old group (β coefficients with 95% confidence interval (95% CI): −1.12 (−2.18, −0.06)), while this trend disappeared after the 50 years. In addition, this association was significantly altered by gender (p for interaction = 0.003). In men, as compared with ≤29 years group, adjusted β coefficient decreased with aging but was only significant in the ≥60 year group (β,−2.16; 95% CI, −4.16 to −0.15). In females, the level of whole blood NAD+ did not significantly differ among five age groups and without the trend as males.ConclusionsAssociation of whole blood NAD+ contents with aging significantly differed in males and females. The loss of blood NAD+ with aging only was observed in males, especially in the male middle-aged population. It is crucial to consider the gender difference in further NAD+ related studies in the future.

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“…Because NAD + levels decline with aging in most tissues and this leads to decreased metabolic function, there is much clinical interest in the use of NAD + precursors as compounds to increase cellular NAD + levels to rejuvenate aged and diseased tissues [ 162 ]. Decreased cellular NAD + levels also blunt beneficial signaling through sirtuin NAD + -dependent protein deacetylases [ 163 ].…”

Section: Interventional Strategies To Correct Dysfunctional Mqc and D...mentioning

confidence: 99%

NADPH and Mitochondrial Quality Control as Targets for a Circadian-Based Fasting and Exercise Therapy for the Treatment of Parkinson’s Disease

Curtis

Seeds²,

Mattson

et al. 2022

Cells

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Dysfunctional mitochondrial quality control (MQC) is implicated in the pathogenesis of Parkinson’s disease (PD). The improper selection of mitochondria for mitophagy increases reactive oxygen species (ROS) levels and lowers ATP levels. The downstream effects include oxidative damage, failure to maintain proteostasis and ion gradients, and decreased NAD+ and NADPH levels, resulting in insufficient energy metabolism and neurotransmitter synthesis. A ketosis-based metabolic therapy that increases the levels of (R)-3-hydroxybutyrate (BHB) may reverse the dysfunctional MQC by partially replacing glucose as an energy source, by stimulating mitophagy, and by decreasing inflammation. Fasting can potentially raise cytoplasmic NADPH levels by increasing the mitochondrial export and cytoplasmic metabolism of ketone body-derived citrate that increases flux through isocitrate dehydrogenase 1 (IDH1). NADPH is an essential cofactor for nitric oxide synthase, and the nitric oxide synthesized can diffuse into the mitochondrial matrix and react with electron transport chain-synthesized superoxide to form peroxynitrite. Excessive superoxide and peroxynitrite production can cause the opening of the mitochondrial permeability transition pore (mPTP) to depolarize the mitochondria and activate PINK1-dependent mitophagy. Both fasting and exercise increase ketogenesis and increase the cellular NAD+/NADH ratio, both of which are beneficial for neuronal metabolism. In addition, both fasting and exercise engage the adaptive cellular stress response signaling pathways that protect neurons against the oxidative and proteotoxic stress implicated in PD. Here, we discuss how intermittent fasting from the evening meal through to the next-day lunch together with morning exercise, when circadian NAD+/NADH is most oxidized, circadian NADP+/NADPH is most reduced, and circadian mitophagy gene expression is high, may slow the progression of PD.

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Age-Dependent Decline of NAD+—Universal Truth or Confounded Consensus?

Cited by 22 publications

References 103 publications

Efficient Assay and Marker Significance of NAD+ in Human Blood

Efficient Assay and Marker Significance of NAD+ in Human Blood

Association of Human Whole Blood NAD+ Contents With Aging

NADPH and Mitochondrial Quality Control as Targets for a Circadian-Based Fasting and Exercise Therapy for the Treatment of Parkinson’s Disease

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