Aging syndrome of a hematopoietic stem cell (HSC) and proposed restoration strategy. In old animals, aging may cause an NAD⁺ deficit by activating poly (ADP-ribose) polymerases (PARPs). The NAD⁺ shortage then decreases the activity of sirtuins, which are anti-aging proteins, thereby promoting the aging cycle. Nicotinamide riboside (NR) replenishes NAD⁺ and corrects the cycle to enhance stem cell maintenance, tissue function, and the unfolded protein response (UPR).