Abstract
Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD+, whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD+ precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD+ production through the NAD+ salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD+ is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD+ precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD+ biosynthesis pathways in mammals, the NAD+ salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD+, have been developed so far. In this review, we will focus on the importance of NAD+ and the possible application of an activator of NAMPT to promote successive aging.
Highlights
Aging is linked to deterioration due to loss of tissue homeostasis and function that leads to the occurrence of age-related diseases such as age-related macular degeneration [1], Alzheimer’s disease [2], artherosclerosis [3], immunosenescence [4], as well as cancer [5]
A treatment that consists of an nicotinamide mononucleotide (NMN) dose of 500 mg/kg body weight/day and administered intraperitoneally for 7–10 consecutive days resulted in an increase of NAD+ levels in liver, skeletal muscle, and white adipose tissue in high fat diet (HFD)-induced diabetic mice and rescued
Our group has generated several lines of transgenic mice overexpressing the human Nampt gene (Nampt-Tg) and has reported that intracellular NAD+ levels in mouse embryonic fibroblast (MEF) derived from these transgenic lines were increased approximately 2-fold [46]
Summary
Aging is linked to deterioration due to loss of tissue homeostasis and function that leads to the occurrence of age-related diseases such as age-related macular degeneration [1], Alzheimer’s disease [2], artherosclerosis [3], immunosenescence [4], as well as cancer [5]. Supplementation of NAD+ and its intermediates through diet has showed promising results in the protection against systemic decline of tissue form and function, as evidenced by the increased resistance to age-related pathogenesis and promotion of healthy aging in vivo. A slight NAD+ increase was observed in skeletal muscle and the cortex of the brain 60 min after NMN administration [55] This demonstrated that supplemented NAD+ precursor can immediately perfuse through tissue barriers and rapidly metabolize into NAD+ in different major organs. A treatment that consists of an NMN dose of 500 mg/kg body weight/day and administered intraperitoneally for 7–10 consecutive days resulted in an increase of NAD+ levels in liver, skeletal muscle, and white adipose tissue in high fat diet (HFD)-induced diabetic mice and rescued. Information on the gerobiotic status (composition of probiotic and parabiotic strains that are able to impact fundamental mechanisms of aging; reviewed by Tsai et al [75]) of aging individuals undergoing NAD+ supplementation should be monitored through the course of treatment to ensure that accurate conclusions of the treatment outcome are made
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