The Role of NAD+ in Rejuvenating Human Body

2020 ◽  
Vol 2 (12) ◽  
pp. 5-20
Author(s):  
Shyamasri Biswas ◽  
Keyword(s):  
Stress Responses ◽  
Accelerated Aging ◽  
Research Direction ◽  
Future Research ◽  
Repair Gene ◽  
Nad Metabolism ◽  
Secondary Messenger ◽  
Age Related ◽  
Dna Repair Gene ◽  
Nad Depletion

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme and considered an essential cofactor in cellular bioenergetics and adaptive stress responses. It is present in all living cells and governs fundamental biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signaling and also in immune-regulatory roles. NAD+ depletion has been a subject of intense research due to the reason that it is associated with hallmarks of aging and age-related diseases, such as metabolic disorders, cancer and neurodegenerative diseases. Recent studies have suggested that physiological and pharmacological interventions that elevate cellular NAD+ levels may slow or even reverse the aspects of aging and also delay the progression of age-related diseases. In this min-review, we have described the roles of NAD+ in relationships to aging and major age-related diseases. The emphasis is on the contribution of NAD+ depletion to aging along with strategies to modulate NAD+ metabolism through physiological and pharmacological pathways. Recent human clinical studies on NAD+ boosting are summarized. We have specifically addressed how boosting NAD+ levels could potentially play an important role as a promising therapeutic strategy to counter aging-associated pathologies and accelerated aging. Finally, a brief perspective on the future research direction is presented.

scholarly journals Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Keisuke Yaku ◽  
Keisuke Okabe ◽  
Maryam Gulshan ◽  
Kiyoshi Takatsu ◽  
Hiroshi Okamoto ◽  
...  
Keyword(s):  
Stress Responses ◽  
Nicotinamide Adenine Dinucleotide ◽  
Biochemical Properties ◽  
Nicotinamide Adenine ◽  
Repair Gene ◽  
Nad Metabolism ◽  
Nad Glycohydrolase ◽  
Dna Repair Gene

Abstract Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that regulates various metabolic pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Additionally, NAD serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD glycohydrolase, and it regulates DNA repair, gene expression, energy metabolism, and stress responses. Many studies have demonstrated that NAD metabolism is deeply involved in aging and aging-related diseases. Previously, we demonstrated that nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD), which are analogs of NAD, are significantly increased in Nmnat3-overexpressing mice. However, there is insufficient knowledge about NGD and NHD in vivo. In the present study, we aimed to investigate the metabolism and biochemical properties of these NAD analogs. We demonstrated that endogenous NGD and NHD were found in various murine tissues, and their synthesis and degradation partially rely on Nmnat3 and CD38. We have also shown that NGD and NHD serve as coenzymes for alcohol dehydrogenase (ADH) in vitro, although their affinity is much lower than that of NAD. On the other hand, NGD and NHD cannot be used as substrates for SIRT1, SIRT3, and PARP1. These results reveal the basic metabolism of NGD and NHD and also highlight their biological function as coenzymes.

scholarly journals Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1234
Author(s):  
Jérôme Raffenne ◽  
Fernando A. Martin ◽  
Rémy Nicolle ◽  
Marina Konta ◽  
Yuna Blum ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Protein Identification ◽  
Molecular Profile ◽  
Global Methylation ◽  
Old Patients ◽  
Molecular Features ◽  
Age Related ◽  
Clinical Difference ◽  
Dna Repair Gene

Pancreatic ducal adenocarcinoma is classically diagnosed in the 7th decade, but approximately 10% of patients are diagnosed under 55 years (y.o.). While the genomic and transcriptomic landscapes of late-onset tumors (LOT) have been described, little is known about early-onset tumors (EOT). Ageing is known to impact DNA methylation and proteome integrity through carbonylation-related oxidative damages. We therefore aimed to assess the global molecular features of EOT. We compared 176 EOT (≤55 y.o.) and 316 LOT (≥70 y.o.) from three distinct surgical cohorts at the clinical/genomic/epigenomic/transcriptomic level. Furthermore, we assessed oxidative stress responses and oxidative proteome damages using 2D gel electrophoresis followed by mass spectrometry protein identification. There was no consistent clinical difference between EOT and LOT across the three cohorts. The mutational landscape of key driver genes and the global methylation profile were similar in the two groups. LOT did display age-related features such as enriched DNA repair gene signatures and upregulation of oxidative stress defenses together with increased proteome carbonylation. However, these age-related differences were more preeminent in non-tumor tissues while tumor proteome and proteome damages were fairly comparable. In conclusion, this multi-omics comparison showed that EOT harbor a comparable molecular profile to that of LOT.

scholarly journals NAD+Metabolism in Aging and Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 105-130 ◽  
Author(s):  
Tyler G. Demarest ◽  
Mansi Babbar ◽  
Mustafa N. Okur ◽  
Xiuli Dan ◽  
Deborah L. Croteau ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Accelerated Aging ◽  
Cancer Therapies ◽  
Nad Metabolism ◽  
Cellular Processes ◽  
Cancer Pathogenesis ◽  
Nicotinamide Mononucleotide ◽  
Age Related

Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.

scholarly journals Epigenetic Regulation of Werner Syndrome Gene in Age-Related Cataract

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xi Zhu ◽  
Guowei Zhang ◽  
Lihua Kang ◽  
Huaijin Guan
Keyword(s):  
Dna Repair ◽  
Histone Modification ◽  
Cpg Island ◽  
Werner Syndrome ◽  
Methylation Status ◽  
Human Lens ◽  
Repair Gene ◽  
Age Related ◽  
Dna Repair Gene ◽  
And Control

Purpose. To examine the promoter methylation and histone modification of WRN (Werner syndrome gene), a DNA repair gene, and their relationship with the gene expression in age-related cataract (ARC) lens.Methods. We collected the lenses after cataract surgery from 117ARC patients and 39 age-matched non-ARC. WRN expression, DNA methylation and histone modification around the CpG island were assessed. The methylation status of Human-lens-epithelium cell (HLEB-3) was chemically altered to observe the relationship between methylation and expression of WRN.Results. The WRN expression was significantly decreased in the ARC anterior lens capsules comparing with the control. The CpG island of WRN promoter in the ARC anterior lens capsules displayed hypermethylation comparing with the controls. The WRN promoter was almost fully methylated in the cortex of ARC and control lens. Acetylated H3 was lower while methylated H3-K9 was higher in ARC anterior lens capsules than that of the controls. The expression of WRN in HLEB-3 increased after demethylation of the cells.Conclusions. A hypermethylation in WRN promoter and altered histone modification in anterior lens capsules might contribute to the ARC mechanism. The data suggest an association of altered DNA repair capability in lens with ARC pathogenesis.

Polymorphisms in the DNA repair gene XRCC1 and age-related disease

2003 ◽  
Vol 124 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Warren Ladiges ◽  
Jesse Wiley ◽  
Alasdair MacAuley
Keyword(s):  
Dna Repair ◽  
Repair Gene ◽  
Related Disease ◽  
Age Related ◽  
Dna Repair Gene

scholarly journals Recent developments and future perspectives in aging and macrophage immunometabolism

2021 ◽  
Vol 8 (3) ◽  
pp. 193-201
Author(s):  
Brandt D. Pence ◽  
◽  
Keyword(s):  
Metabolic Reprogramming ◽  
Future Research ◽  
Low Grade ◽  
Future Perspectives ◽  
Nad Metabolism ◽  
Promising Strategy ◽  
Age Related ◽  
Recent Developments ◽  
Monocytes And Macrophages ◽  
Low Grade Inflammation

<abstract> <p>Aging is the strongest contributor to the development and severity of many chronic and infectious diseases, primarily through age-related increases in low-grade inflammation (inflammaging) and decreases in immune function (immunosenescence). Metabolic reprogramming in immune cells is a significant contributor to functional and phenotypic changes in these cells, but little is known about the direct effect of aging on immunometabolism. This review highlights several recent advances in this field, focusing on mitochondrial dysfunction, NAD+ metabolism, and therapeutic reprogramming in aged monocytes and macrophages. Perspectives on opportunities for future research in this area are also provided. Targeting immunometabolism is a promising strategy for designing therapeutics for a wide variety of age-related diseases.</p> </abstract>

ECONOMIC GROWTH ANALYSIS: A STUDY ON MALAYSIAN MARKET

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Suhaily Maizan Abdul Manaf ◽  
Shuhada Mohamed Hamidi ◽  
Nur Shafini Mohd Said ◽  
Siti Rapidah Omar Ali ◽  
Nur Dalila Adenan
Keyword(s):  
Economic Growth ◽  
Foreign Direct Investment ◽  
Direct Investment ◽  
Inflation Rate ◽  
Government Expenditure ◽  
Correlation Method ◽  
Research Direction ◽  
Least Square ◽  
Future Research ◽  
Internal And External Factors

Economic performance of a country is mostly determined by the growth and any other internal and external factors. In this study, researchers purposely focused on Malaysian market by examining the relationship between export, inflation rate, government expenditure and foreign direct investment towards economic growth in Malaysia by applying the yearly data of 47 years from 1970 to 2016 using descriptive statistics, regression model and correlation method analysis. By applying Ordinary Least Square (OLS) method, the result suggests that export, government expenditure and foreign direct investment are positively and significantly correlated with the economic growth. However, inflation rate has negative and insignificant relationship with the economic growth. The outcome of the study is suggested to be useful in providing the future research direction towards the economic growth in Malaysia. Keywords: economic growth; export; inflation rate; government expenditure

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