In this paper Sinclair et al demonstrated that when NAD+ ( a product of mitochondrion, Kreb's cycle) is given to old mice it will improve the slowly developed vascular blood flow problems in various organs which were starting to fail one by one (cycle of morbidity in old people). The best way to give more NAD+ is to improve NAD+ production by improving mitochondrion function in these old animals ( and in humans ?). by reducing iron content accumulated in old mitochondria. I am sure Sinclair will repeat this study soon with PBT434. What kind of possibilities there is if PBT434 works as I think !
Cell. 2018 Mar 22;173(1):74-89.e20. doi: 10.1016/j.cell.2018.02.008. Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging.
A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1-SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.
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