scholarly journals Emerging Nutritional Interventions for Age-Associated Cellular Decline

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 765-765
Author(s):  
Anurag Singh
Keyword(s):  
Metabolic Demand ◽  
Vitamin B3 ◽  
Double Blind ◽  
Progressive Decline ◽  
Nutritional Interventions ◽  
Nicotinamide Riboside ◽  
Optimal Functioning ◽  
Urolithin A ◽  
Cellular Bioenergetics ◽  
High Metabolic Demand

Abstract Aging is associated with a progressive decline in cellular health leading to dysfunction in organs with a high metabolic demand. A key feature of age associated cellular decline is impairment of mitochondrial quality control pathways such as mitophagy. Deficits in optimal functioning of these pathways results in a compromise in cellular bioenergetics that ultimately leads to mitochondrial dysfunction. Promising nutritional interventions have emerged that boost mitochondrial health such as nicotinamide riboside (vitamin B3 precursor) and Urolithin A (gut metabolite of compounds found in pomegranates), that act via different mechanisms of action to improve overall mitochondrial health. Recent literature on the evidence behind these interventions will be presented and discussed during this symposium. We will also share recent clinical evidence from double-blind placebo-controlled studies with Urolithin A. Our results suggest that nutritional interventions such as Urolithin A are promising approaches that can be employed to manage age associated cellular decline.

scholarly journals Equilibrative Nucleoside Transporters Mediate the Import of Nicotinamide Riboside and Nicotinic Acid Riboside into Human Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1391
Author(s):  
Andrey Kropotov ◽  
Veronika Kulikova ◽  
Kirill Nerinovski ◽  
Alexander Yakimov ◽  
Maria Svetlova ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Mammalian Cells ◽  
Experimental Models ◽  
The Body ◽  
Nucleoside Transporters ◽  
Hek293 Cells ◽  
Nucleoside Transporter ◽  
Vitamin B3 ◽  
Animal Cells ◽  
Nicotinamide Riboside

Nicotinamide riboside (NR), a new form of vitamin B3, is an effective precursor of nicotinamide adenine dinucleotide (NAD+) in human and animal cells. The introduction of NR into the body effectively increases the level of intracellular NAD+ and thereby restores physiological functions that are weakened or lost in experimental models of aging and various pathologies. Despite the active use of NR in applied biomedicine, the mechanism of its transport into mammalian cells is currently not understood. In this study, we used overexpression of proteins in HEK293 cells, and metabolite detection by NMR, to show that extracellular NR can be imported into cells by members of the equilibrative nucleoside transporter (ENT) family ENT1, ENT2, and ENT4. After being imported into cells, NR is readily metabolized resulting in Nam generation. Moreover, the same ENT-dependent mechanism can be used to import the deamidated form of NR, nicotinic acid riboside (NAR). However, NAR uptake into HEK293 cells required the stimulation of its active utilization in the cytosol such as phosphorylation by NR kinase. On the other hand, we did not detect any NR uptake mediated by the concentrative nucleoside transporters (CNT) CNT1, CNT2, or CNT3, while overexpression of CNT3, but not CNT1 or CNT2, moderately stimulated NAR utilization by HEK293 cells.

scholarly journals Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing

2022 ◽  
Vol 23 (2) ◽  
pp. 649
Author(s):  
Siarhei A. Dabravolski ◽  
Vasily N. Sukhorukov ◽  
Vladislav A. Kalmykov ◽  
Nikolay A. Orekhov ◽  
Andrey V. Grechko ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Molecular Chaperones ◽  
Heat Shock Protein 90 ◽  
Misfolded Proteins ◽  
Heart Cells ◽  
Metabolic Demand ◽  
Heart Protection ◽  
High Metabolic Demand

Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.

scholarly journals Optimizing mitochondrial maintenance in extended neuronal projections

2021 ◽  
Vol 17 (6) ◽  
pp. e1009073
Author(s):  
Anamika Agrawal ◽  
Elena F. Koslover
Keyword(s):  
Steady State ◽  
Neurodegenerative Disorders ◽  
Quantitative Model ◽  
Organelle Transport ◽  
Optimal Distribution ◽  
Metabolic Demand ◽  
Mitochondrial Homeostasis ◽  
Fresh Material ◽  
New Material ◽  
High Metabolic Demand

Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mitochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an interplay between a stationary pool localized to sites of high metabolic demand and a motile pool capable of delivering new material. Interchange between these pools can occur via transient fusion / fission events or by halting and restarting entire mitochondria. Our quantitative model of neuronal mitostasis identifies key parameters that govern steady-state mitochondrial health at discrete locations. Very infrequent exchange between stationary and motile pools optimizes this system. Exchange via transient fusion allows for robust maintenance, which can be further improved by selective recycling through mitophagy. These results provide a framework for quantifying how perturbations in organelle transport and interactions affect mitochondrial homeostasis in neurons, a key aspect underlying many neurodegenerative disorders.

STATUS OF OXIDANT (MDA) ANTIOXIDANT (SOD) IN FIRST AND THIRD TRIMESTER OF NORMAL PREGNANCY IN TERTIARY CENTER OF CENTRAL INDIA

2021 ◽  
pp. 12-14
Author(s):  
Tamrakar Seema ◽  
Sachdeva Payasvi ◽  
Tripathi Rashmi
Keyword(s):  
Oxidative Stress ◽  
Pregnant Women ◽  
Central India ◽  
Normal Pregnancy ◽  
Metabolic Demand ◽  
Third Trimester ◽  
Dynamic Changes ◽  
Tertiary Center ◽  
Antioxidant Supplements ◽  
High Metabolic Demand

INTRODUCTION: Pregnancy is associated with high metabolic demand and increased demand for tissue oxygen. Consequently increased production of reactive oxygen species. This leads in increased oxidative stress and decreases antioxidant status during gestational age of normal pregnant women. Aim: Aim of this study was to evaluate the level of oxidant and antioxidant in 1st and 3rd trimester of normal pregnant women. MATERIAL AND METHODS: The present study included total 150 cases attended ANC Clinic at the department of Gynae LNMC & J K Hospital was screened for the study. Level of MDA was estimated by Jean et al and SOD was Marklund and Marklund. RESULTS: Findings were, that there was signicantly increase in Malondialdehyde levels (p<0.001) and signicantly decrease in superoxide dismutase activities (P<0.001) in 1st and 3rd trimester of normal pregnant women. Conclusion: present study concludes that there was difference in oxidative status due to dynamic changes. During pregnancy oxidative stress is increased and antioxidant decreased that can be fatal to the health of the mother and the fetus. Therefore antioxidant supplements should be prescribed in early pregnancy to prevent the overwhelming of oxidative stress in pregnant females.

scholarly journals Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects.

2021 ◽  
Author(s):  
Ekaterina Podyacheva ◽  
Yana Toropova
Keyword(s):  
High Efficiency ◽  
Experimental Models ◽  
Symptomatic Therapy ◽  
Vitamin B3 ◽  
Nicotinamide Riboside ◽  
Independent Form ◽  
Oncological Diseases ◽  
Hematological Tumors ◽  
Late Stages ◽  
Doxorubicin Cardiomyopathy

Abstract Despite the progress in the development of new anticancer strategies, cancer is rapidly spreading around the world and remains one of the most common diseases. At the same time, oncological diseases are detected in patients with late stages of the course in the overwhelming majority of cases. This fact necessitates chemotherapy both as part of a combination and in the view of an independent form of treatment. For more than 40 years, doxorubicin has been widely used in the treatment of solid and hematological tumors. At the same time, the problem of its cardiotoxicity remains unresolved, despite the high efficiency of this drug. Symptomatic therapy is used as a treatment for side-effects of doxorubicin or pathological conditions that have already appeared on their background. To date, there are no treatment methods for doxorubicin cardiomyopathy as such. A drug such as nicotinamide riboside can play an important role in solving this problem. Nicotinamide riboside is a pyridine nucleoside similar to vitamin B3 that acts as a precursor to NAD+. There are no such works in cardiomyopathy, despite the abundance of works devoted to the mechanisms of realization of the effects of nicotinamide riboside in various pathologies. The review analyzes information about the effects of NR on various experimental models of pathologies, its role in the synthesis of NAD+, and also considers the possibility and prospects of its use for the prevention of doxorubicin cardiomyopathy.

scholarly journals Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial

2019 ◽  
Author(s):  
Yasir S Elhassan ◽  
Katarina Kluckova ◽  
Rachel S Fletcher ◽  
Mark Schmidt ◽  
Antje Garten ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Stress ◽  
Human Muscle ◽  
Resonance Spectroscopy ◽  
Metabolic Dysfunction ◽  
Double Blind ◽  
Chronological Aging ◽  
Nicotinamide Riboside ◽  
Anti Inflammatory ◽  
Aged Subjects

SUMMARYNAD+ is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+ levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.

scholarly journals Post-chemotherapy maintenance treatment by nicotinamide riboside, a poly ADP ribose polymerase 1 inhibitor, in BRCA mutated advanced ovarian cancer – A perspective

2021 ◽  
Vol 0 ◽  
pp. 1-4
Author(s):  
Mukul Arvind Gharote ◽  
Amruta Ashok Deshpande
Keyword(s):  
Maintenance Treatment ◽  
Indian Subcontinent ◽  
Advanced Ovarian Cancer ◽  
Current Evidence ◽  
High Dose ◽  
Maintenance Chemotherapy ◽  
Vitamin B3 ◽  
Nicotinamide Riboside ◽  
Toxic Potential ◽  
Parp 1

Poly ADP ribose polymerase 1 (PARP-1) inhibitors are approved for post-chemotherapy maintenance in BRCA mutated ovarian carcinoma. Various PARP-1 inhibitors such as olaparib, rucaparib, niraparib, and veliparib are approved for this indication. These PARP-1 inhibitors are costly as well as having toxic potential, anemia, and neutropenia is the major side effects. Most of the middle-aged women in Indian subcontinent are anemic and prescription of PARP-1 inhibitors is tricky in such conditions, besides their cost is at times unaffordable as maintenance chemotherapy. Hence, we need an affordable yet lesser toxic PARP-1 inhibitor to solve this problem. Nicotinamide, a vitamin B3 amide can be re-purposed as PARP-1 inhibitor. Nicotinamide, albeit at a higher dose, can be efficacious as well as economical in its use as maintenance chemotherapy. It has toxic potential but the toxicity is both rare and manageable. We need a clinical trial for this purpose. Following perspective is on the current evidence on high dose nicotinamide and it is re-purposing as PARP-1 inhibitor.

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