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Anti-Aging and Regenerative Medicine
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
Hot in anti-aging news is MIT's Leonard Guarente, who claims to have found the fountain-of-youth in his pill called Basis. One of the pioneers and global champions in anti-aging research, Guarente has discovered the single gene that is concerned with these sirtuins (Wallace 2016). Basis, using precursors for NAD(+), that is, nicotinamide riboside (250 mg) and pterostilbene (50 mg), tricks the body into thinking that it is starving, without the person actually feeling hungry. Anti-aging research already knows that starving or restricted-calorie diets lead to increased lifespans. Pterostilbene has shown reduction in markers of inflammation, cellular stress, and Alzheimer's disease (Chang et al. 2012). Elysium health, the company producing Basis, claims to be heavily evidence backed and is running a trial with 120 participants between the ages of 60 and 80. The firm insists to never make a claim that isn't substantiated by evidence, but the combination of anti-aging substances found in the pill doesn't seem to have any evidence.
Poly (ADP-Ribose) Polymerase — A Nonhistone Nuclear Protein
Published in Lubomir S. Hnilica, Chromosomal Nonhistone Proteins, 2018
The enzyme catalyzes the successive transfer of the ADP-ribose moiety of nicotinamide adenine-dinucleotide (NAD) to generate a covalently bound homopolymer of poly ADP-ribose on nuclear protein acceptors. The enzyme has an absolute requirement for DNA, histone, and the divalent cation, Mg2+ and cleaves the NAD at the nicotinamide-ribose bond (bond energy ~ 34 kJ/mol).
Mitochondrial Dysfunction, Immune Systems, Their Diseases, and Possible Treatments
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Elise Jacquin, Eric Hervouet, Michaël Boyer-Guittaut
Inherited or sporadic mitochondrial diseases linked to mutations or deletions in mitochondrial DNA lead to the impairment of the ETC and decreased energy production. Mitochondrial diseases are considered as rare diseases but the symptoms develop early and there are currently no cures. One way to treat these young patients would be to activate mitochondria biogenesis in order to increase the overall number of mitochondria in the body. Previous studies have shown that Nicotinamide Riboside (NR), a functional B3 vitamin and a NAD+ natural precursor, might be able to activate mitochondrial biogenesis, via the PGC-1α factor, and therefore increase energy production. It has, for example, been shown in a mouse model of mitochondrial myopathy that administration of NR led to the delay of disease progression and that this effect was dependent on mitochondrial biogenesis in skeletal muscle and adipose tissue.86 One clinical trial posted in 2018 (NCT03432871) will target the potential of this compound to increase mitochondrial biogenesis (respiratory chain enzyme analysis and mtDNA quantification) in patients with Progressive External Ophthalmoplegia (PEO), a condition linked to a single deletion of mtDNA. Interestingly, this compound has also be shown to modulate NRLP3 inflammasome and to reduce inflammation in a model of T2DM in rodents.87 In this study, the authors showed that administration of NR rescued mitochondrial integrity in the liver of obese and diabetic mice, inhibited NRLP3 and Caspase 1 activation and decreased pro-inflammatory cytokines levels (TNFα and IL-1) in hepatic cells.
Protective Effects of Nicotinamide Riboside on H2O2-induced Oxidative Damage in Lens Epithelial Cells
Published in Current Eye Research, 2021
Biting Zhou, Guangyu Zhao, Yihua Zhu, Xiaole Chen, Nanwen Zhang, Juhua Yang, Hong Lin
Nicotinamide riboside (NR) is adirect exogenous precursor of NAD+.11 It freely penetrates the cell membrane and enters cells to synthesize NAD+, which enhances retinal metabolism, reduces photoreceptor cell death, improves visual function,12,13 and prolongs the lifespan of model organisms.14 NR has been extensively studied in the fields of ageing and neurodegenerative diseases.15 However, researchers have not clearly determined whether NR reduces oxidative damage in lens epithelial cells and its underlying mechanism. In this study, ahuman lens epithelial cell line was cultured, and hydrogen peroxide (H2O2) was used to induce oxidative damage. NR was used as atherapeutic intervention. We observed changes in cell viability, apoptosis, reactive oxygen species (ROS) levels, antioxidant enzyme activity and the mitochondrial membrane potential (MMP) and explored the possible mechanisms of action of NR.
Oral delivery of carrier-free dual-drug nanocrystal self-assembled microspheres improved NAD+ bioavailability and attenuated cardiac ischemia/reperfusion injury in mice
Published in Drug Delivery, 2021
Hongfei Nie, Yarong Zhang, Haiyang Yu, Hong Xiao, Tao Li, Qian Yang
Nicotinamide riboside (NR) is a pyridine nucleoside form of vitamin B3, which naturally exists in milk and is a candidate of dietary supplement (Trammell et al., 2016; Martens et al., 2018). Normally, NR is converted to nicotinamide mononucleotide (NMN) by the biocatalysis of nicotinamide riboside kinases (NRK1,2), and subsequently converted to NAD+ by nicotinamide mononucleotide adenylyltransferase (NMNAT), serving as a NAD+ precursor (Trammell et al., 2016). Oral supplementation with NR molecules has been proven to increase the NAD+ level in heart, liver and skeletal muscle, as well as oxidative metabolism in high-fat diet-induced obesity (Cantó et al., 2012; Khan et al., 2014; Diguet et al., 2018; Schöndorf et al., 2018; Elhassan et al., 2019). However, oral administrated NR is quickly degraded to nicotinamide (NAM) in the gastrointestinal tract and liver, and is undetectable in blood stream within 1 hour (Liu et al., 2018). Thus, prolonging NAD+ bioavailability is vital in NR-based therapy.
Emerging pharmacological strategies for the management of chemotherapy-induced peripheral neurotoxicity (CIPN), based on novel CIPN mechanisms
Published in Expert Review of Neurotherapeutics, 2020
Andreas A. Argyriou, Jordi Bruna, Susanna B. Park, Guido Cavaletti
Similarly, there are approaches to target the NAD+ pathway. Nicotinamide riboside is a NAD+ precursor which acts to increase NAD+ levels, potentially reducing oxidative stress and promoting mitochondrial function. As discussed, there is evidence that CIPN is linked to reduced NAD+ through activation of the enzyme SARM1 [69] and accordingly nicotinamide riboside may prevent axonal degeneration via SARM1 pathways. There is experimental evidence from animal models that nicotinamide riboside supplementation protects against paclitaxel neurotoxicity [70]. Nicotinamide riboside is currently under trial in a Phase II study for prevention of paclitaxel-induced CIPN (NCT03642990), with the NCI-CTCAE grade as the primary outcome measure, although a composite objective scale and PROs are included as secondary outcomes.