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Coronary Artery Disease
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2022
One of the newer antiaging molecules is referred to NMN (nicotinamide mononucleotide). This metabolite of vitamin B3 is found throughout our bodies and in some healthy foods like broccoli, which is a popular vegetable in the Mediterranean diet. NMN is a precursor to the vitally important molecule NAD+ which not only supports multiple metabolic functions but also healthy aging. The problem is that NAD+ levels decline by as much as 50% as we reach middle age. Several of my colleagues, including myself, have taken NMN in supplemental form to help bolster the natural production of NAD+ which ameliorates the inexorable decline of aging. In the mouse model, the administration of NMN at extremely high doses was found to be safe and well-tolerated while mitigating age-associated physiological decline.42 This is one substance you should keep on your radar as many targeted nutritional supplement suppliers will probably market this vital compound. Such science-based genetic nutraceuticals like NMN and others will be highlighted at future medical symposiums and conferences as targeted genetic supports are gaining momentum in the scientific community.
Food Interactions, Sirtuins, Genes, Homeostasis, and General Discussion
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Other plant polyphenols inducing sirtuin activation include piceatannol, kaempferol, quercetin, fisetin, butein, catechins, and proanthocyanidins. They are found in tea leaves, grapes, galangal, persimmon, apple, orange, berries, cherries, nuts (walnut), beans (soybeans), olive oil, cocoa and its byproduct chocolate, ginkgo, mangosteen, pepper, chili, parsley, kale, and more. Some natural food sources rich in nicotinamide mononucleotide (NMN), a precursor of NAD+, are: edamame (immature soybeans), avocado, broccoli, cabbage, whole cucumber peel and seed, and tomato (81, 101). Vitamin B3 is also a furnisher of NAD+, an essential coenzyme of sirtuins (75).
Adenine Dinucleotide
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Richard F. Mestayer, Hyla Cass
Still other researchers are investigating the role of NAD+ in DNA repair—an ongoing process given the constant onslaught our bodies are subjected to via stress, environmental toxins, EMFs and RFs, poor diet, and more.
A mechanistic overview of spinal cord injury, oxidative DNA damage repair and neuroprotective therapies
Published in International Journal of Neuroscience, 2023
Jaspreet Kaur, Aditya Mojumdar
Oxidative DNA damage triggers multiple signalling pathways leading to apoptosis. PARP1 is the main player in triggering apoptotic cascades and is comprised of an N-terminal DNA binding domain and a catalytic domain that binds nicotinamide adenine dinucleotide (NAD) [114]. PARP1 binds to the SSB and catalyzes the cleavage of NAD+ to generate nicotinamide and ADP-ribose. PARP1 overactivation due to enhanced DNA damage leads to the depletion of NAD+, resulting in mitochondrial disfunction and depletion in cellular energy [115]. The fact that both in-vitro and in-vivo studies have reported reduced levels of oxidative damage and cell death upon the replenishment of NAD+ can be of therapeutic interest [116,117]. Upon PARP1 activation post-DNA damage, AIF translocates from the mitochondria to the nucleus triggering apoptosis. PARP inhibition attenuates AIF migration and protects neurons from apoptotic death [118,119]. Another PARP mediated cascade involves activation of calpains and Bax, however not much is known about this pathway in neuronal cells [120]. Role of proteases like caspases (cystine-aspartate proteases) has been much studied in apoptosis. A recent study reported differences in responses of human neurons to injury and death stimuli compared to other animal neurons in cell culture [121]. These apoptotic cascades have been reviewed in detail by Li and his colleagues [91].
TNB-738, a biparatopic antibody, boosts intracellular NAD+ by inhibiting CD38 ecto-enzyme activity
Published in mAbs, 2022
Harshad S. Ugamraj, Kevin Dang, Laure-Hélène Ouisse, Benjamin Buelow, Eduardo N. Chini, Giulia Castello, James Allison, Starlynn C Clarke, Laura M. Davison, Roland Buelow, Rong Deng, Suhasini Iyer, Ute Schellenberger, Sankar N. Manika, Shipra Bijpuria, Astrid Musnier, Anne Poupon, Maria Cristina Cuturi, Wim van Schooten, Pranjali Dalvi
CD38 is a 45 kDa type II transmembrane protein expressed on immune cells, including macrophages, T cells, B cells, and natural killer (NK) cells, and is prominently upregulated on activated immune cells, thus serving as a biomarker for active infections, inflammatory diseases, autoimmune conditions, and inflammation associated with aging, or “inflammaging”.7,8 CD38 is an ecto-enzyme that hydrolyzes nicotinamide adenine dinucleotide (NAD+) to form adenine diphosphate ribose (ADPR) and nicotinamide (NAM); secondarily, it degrades NAD+ via cyclase activity yielding cyclic adenine dinucleotide (cADPR). Other substrates of CD38 include nicotinamide adenine dinucleotide phosphate (NADP+) and nicotinamide mononucleotide (NMN), a critical precursor of NAD+ in the salvage pathway, preventing its uptake into cells and its conversion to NAD+ intracellularly.4 NAD+ plays a crucial role in several metabolic processes that maintain energy balance, DNA repair, and signaling.9 Decreases in NAD+ are associated with natural aging, and NAD+ boosting is associated with increased life- and health-spans in animals.10 Therefore, TNB-738-mediated inhibition of CD38 represents a promising approach to treat a plethora of acute and chronic conditions associated with NAD+ decline.
Gut associated metabolites and their roles in Clostridioides difficile pathogenesis
Published in Gut Microbes, 2022
Andrea Martinez Aguirre, Joseph A. Sorg
Although Stickland metabolism is well-characterized in Clostridium sticklandii,60 this alternative metabolic pathway in other Clostridial species has just recently been elucidated. Bouillaut et al.59 analyzed the C. difficile glycine and proline reduction operons and their activity in the reductive pathway of Stickland metabolism. A mutation in the prdB subunit of the proline reductase enzyme resulted in a decrease in growth in rich media, but a mutation in a grdA mutant did not affect growth in rich medium.59 Additionally, the authors characterize the sigma-54 dependent activator, PrdR that acts as a mediator for PrdB-dependent activation and proline-dependent toxin repression.59 In addition, given the role the Stickland reductive branch has in regenerating NAD+ for the cell, the redox dependent transcriptional repressor, Rex, has a role in proline-dependent regulation and is controlled by PrdR in C. difficile.61 Using DNA binding assays and qRT-PCR, the authors found that proline seems to be the preferred amino acid for regeneration of NAD+. In presence of excess proline, PrdR stimulates proline reductase expression and simultaneously Rex represses the glycine reductase gene grdE. NADH is then oxidized and, as a result, the ratio of NADH/NAD+ is low. Alternatively, when levels of proline are low, the NADH/NAD+ ratio increases and the high levels of NADH prevents Rex from repressing glycine reductase expression (Figure 2(b,c)).61