The stages in life commence when born, growing, maturing and aging. Unraveling the mysteries of aging, as a person ages they loose the capacity to repair DNA leading to cancer and overall deterioration. The depletion of the coenzyme NAD+ (nicotinamide adenine dinucleotide) is highly important in cellular bioenergetics and adaptive stress response, not to mention IDH1(Isocitrate dehydrogenase 1) gliomas are depends upon the canonical coenzyme NAD+ for survival.5 Depletion of NAD+ may induce to a variety of chronic diseases such as Alzheimer’s, Parkinson’s disease, cardiovascular disease and even muscle atrophy. NAD+ was primarily discovered over 110 years ago as a cozymase needed for fermentation. In 1930 Nobel price winner Dr. Hans von Euler-Chelpin stated that cozymase NAD+ is an important activator for many metabolic pathways, like glycolysis, fatty acid β-oxidation, and tricarboxylic acid cycle.1 In the reduced form of NADH is a primary hydride donor in the production of ATP. Recent studied have shown that NAD+ in autophagy and mitophagy (selective degradation on mitochondria) impairments of lysosome-targeting and recycling mechanism end up in the accumulation of damaged molecules and mitochondria that leads to cell dysfunction or death.2 What are the resolutions? Sir2, a silent information regulator 2 that is a NAD-dependent histone deacetylase involved regulating apoptosis, stress tolerance, insulin resistance and fat metabolism.3 So far this longevity gene product has been proved to work on 10.5 in mice as early as embryonic day.3 The drug is under animal trials, long before it could reach clinical trials. However, the investigation of the effects of Beta-Hydroxy-Beta-Methylbutyrate on Glucose Handling in Older and Younger Men is an ongoing clinical trial that will ne completed by January 2018. The primary outcomes is to intervene of prevent Matsu index of insulin resistance. This is being done with a time frame of 180 minutes after a 75g oral glucose load, assessed from arterialized venous blood. (Cite FDA). The intentions are to examine how a person handles glucose by providing them with a dietary supplement or a placebo. A person aging is associated with reduction in fitness, exercising also determines how well their blood vessels work. Eligibility consist of being within the age group of 18 to 85 years (Adult, Senior), Male and may or may not be a healthy candidate. Exclusions include: current participation in a formal exercise regime, A BMI < 18 or >32 Kg m2, Active cardiovascular disease (uncontrolled hypertension, angina, heart failure, significant arrhythmia, right to left cardiac shunt,or recent cardiac event), intaking beta-adrenergic blocking agents, cerebrovascular disease, respiratory disease, Metabolic disease active inflammatory bowel or renal disease, Malignancy, clotting dysfunction, Musculoskeletal or neurological disorder, and Family history of early death from cardiovascular disease.4 The location of this clinical trial is in the University of Nottingham with the involvement of Philip Herrod, Beth Philiips, and Jon Lund, from the united Kingdom. In this particular clinical trial the ethical implications consist of assurance of the best diagnostic and therapeutic method, however with the placebo-controlled trials not everyone is receiving the best treatment.
In 2017, Harvard scientist have been looking at IDH1-mutant in order to survive depend on the coenzyme of NAD+. In Chemotherapy-induced DNA damage base excision repair (BER) PARP activation consumes NAD+. In order to stop depletion, scientist hypothesized a strategy to combine NAD+ and alkylating chemotherapeutic agent temozolomide, leasing cytotoxiticy in mutant IDH1 cancer cells. For further knowledge on the impact of temozolomide in NAD+ metabolism, patients obtained xenografts and engineered mutant IDH1-expressing cell lines were exposed to temozolomide, in vivo and in vitro. They found that combination regimens targeting non redundant NAD+ pathways yield potent anticancer efficacy in vivo and that IDH1-mutant have a different response metabolic stress responses to chemotherapy induced DNA damage.5 Eventually minimizing treatment toxicity and durability improvement.
NAD+ is a very important coenzyme in the mitochondria function that when a person age its levels decrease it can arise severe health implications. When exercise is constant it boost up NAD+, therefore slowing aging process.