The Effects Of Nicotinamide Adenine Dinucleotide On The Aging Process Of Mice

Aging is recognized as an irreversible process that is characterized by progressive tissue degeneration and atrophy,metabolic dysfunction,obesity and the development of other age-related diseases.Many studies have shown that,in humans,the organ nicotinamide adenosine dinucleotide(NAD~+)levels decline with age,which is associated with age-related diseases.NAD~+,a cofactor for hundreds of metabolic reactions in cells,plays an essential role in metabolism,DNA repair,and aging.NAD~+also enables energy generation through glycolysis and mitochondrial respiration to support cell growth and survival.There are three pathways for the NAD~+synthesis in cells to maintain NAD~+balance.Many groups have investigated NAD~+and its precursors for their anti-aging effects and treatment of age-related diseases.In addition,several ongoing clinical trials are evaluating the safety and efficacy of NAD~+and its precursors.Whether NAD~+could delay aging and improve host health remains a controversial issue,mainly due to the lack of a goodbiomarker for aging.However,the DNA methylation clock allows us to accurately calculate the biological age of the host,which should enable us to examine the effectiveness of NAD~+better.In this study,the biological ages of mice treated with NAD~+were calculated based on three methylation sites in Prima 1,Hsf 4 and Kcns 1.Moreover,we also performed the RNA sequencing in heart tissue and 16S r DNA sequencing to assess the effects of NAD~+on age-related gene expression and gut microbiota,which may also affect aging.Although the results showed that there was no statistically significant difference between the treated and untreated group animals,a clearly downward trend of the NAD~+group was noticed.Surprisingly,NAD~+treatment promotes weight loss with darker hair and no humpback in male C57BL/6J mice.In addition,transcriptome analysis show that the expression levels of age-related Creb5,Fn1 and Gck were significantly downregulated.Previous reports showed the low levels of Creb5 expression are associated with weight loss in mice.The expression of Fn1 and Mmp-3 genes associated with inflammation were also significantly down-regulated.Furthermore,gut microbiome analysis with 16S r DNA sequencing showed that the levels of g＿Lactobacillus and g＿Bifidobacterium were significantly increased in NAD~+treated group,suggesting that NAD~+improved the host intestinal microflora,which may improve the health of the host.