scholarly journals Age-Dependent Decline of NAD+ - Universal Truth or Confounded Consensus?

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 101
Author(s):  
A. Augusto Peluso ◽  
Mads V. Damgaard ◽  
Marcelo A. S. Mori ◽  
Jonas T. Treebak
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Electron Transport Chain ◽  
Cell Type ◽  
Nad Metabolism ◽  
C Elegans ◽  
Age Related ◽  
Transport Chain ◽  
Age Dependent ◽  
Metabolic Reactions ◽  
Universal Truth

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with age. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to increase NAD+ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human), to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that, despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support such claims is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD metabolism during aging and should provide a foundation for better pharmacological targeting of relevant tissues.

scholarly journals Age-Dependent Decline of NAD+ - Universal Truth or Confounded Consensus?

2021 ◽  
Author(s):  
Augusto Peluso ◽  
Mads Vargas Damgaard ◽  
Marcelo Alves Mori ◽  
Jonas Thue Treebak
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Electron Transport Chain ◽  
Cell Type ◽  
Nad Metabolism ◽  
C Elegans ◽  
Age Related ◽  
Transport Chain ◽  
Age Dependent ◽  
Metabolic Reactions ◽  
Universal Truth

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with time. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to boost NAD+ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human) to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support it is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies aimed to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD+ during aging and should provide a foundation for better pharmacological targeting of relevant tissues.

scholarly journals Age-Dependent Loss of Mitochondrial Function in Epithelial Tissue Can Be Reversed by Coenzyme Q10

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Daniel Schniertshauer ◽  
Daniel Gebhard ◽  
Jörg Bergemann
Keyword(s):  
Electron Transport ◽  
Coenzyme Q10 ◽  
Mitochondrial Respiration ◽  
Electron Transport Chain ◽  
Epithelial Tissue ◽  
Atp Production ◽  
Transport Chain ◽  
Respiratory Parameters ◽  
Age Dependent ◽  
Theory Of Aging

The process of aging is characterized by the increase of age-associated disorders as well as severe diseases. Due to their role in the oxidative phosphorylation and thus the production of ATP which is crucial for many cellular processes, one reason for this could be found in the mitochondria. The accumulation of reactive oxygen species damaged mitochondrial DNA and proteins can induce mitochondrial dysfunction within the electron transport chain. According to the “mitochondrial theory of aging,” understanding the impact of harmful external influences on mitochondrial function is therefore essential for a better view on aging in general, but the measurement of mitochondrial respiration in skin cells from cell cultures cannot completely reflect the real situation in skin. Here, we describe a new method to measure the mitochondrial respiratory parameters in epithelial tissue derived from human skin biopsies using a XF24 extracellular flux analyzer to evaluate the effect of coenzyme Q10. We observed a decrease in mitochondrial respiration and ATP production with donor age corresponding to the “mitochondrial theory of aging.” For the first time ex vivo in human epidermis, we could show also a regeneration of mitochondrial respiratory parameters if the reduced form of coenzyme Q10, ubiquinol, was administered. In conclusion, an age-related decrease in mitochondrial respiration and ATP production was confirmed. Likewise, an increase in the respiratory parameters by the addition of coenzyme Q10 could also be shown. The fact that there is a significant effect of administered coenzyme Q10 on the respiratory parameters leads to the assumption that this is mainly caused by an increase in the electron transport chain. This method offers the possibility of testing age-dependent effects of various substances and their influence on the mitochondrial respiration parameters in human epithelial tissue.

Proficiency testing for mitochondrial electron transport chain (ETC) enzyme assays using C. elegans

Mitochondrion ◽  
2011 ◽  
Vol 11 (4) ◽  
pp. 658
Author(s):  
Xiulian Chen ◽  
David R. Thorburn ◽  
Lee-Jun Wong ◽  
Georgirene D. Vladutiu ◽  
Richard Haas ◽  
...  
Keyword(s):  
Electron Transport ◽  
Proficiency Testing ◽  
Electron Transport Chain ◽  
Enzyme Assays ◽  
Mitochondrial Electron Transport Chain ◽  
C Elegans ◽  
Transport Chain

scholarly journals Effects of Aging on Activities of Mitochondrial Electron Transport Chain Complexes and Oxidative Damage in Rat Heart

2011 ◽  
pp. 281-289 ◽  
Author(s):  
Z. TATARKOVÁ ◽  
S. KUKA ◽  
P. RAČAY ◽  
J. LEHOTSKÝ ◽  
D. DOBROTA ◽  
...  
Keyword(s):  
Electron Transport ◽  
Oxidative Damage ◽  
Electron Transport Chain ◽  
Molecular Mechanisms ◽  
Thiol Group ◽  
Mitochondrial Electron Transport Chain ◽  
Age Related ◽  
Transport Chain ◽  
Old Rats ◽  
Major Factors

Mitochondrial dysfunction and accumulation of oxidative damage have been implicated to be the major factors of aging. However, data on age-related changes in activities of mitochondrial electron transport chain (ETC) complexes remain controversial and molecular mechanisms responsible for ETC dysfunction are still largely unknown. In this study, we examined the effect of aging on activities of ETC complexes and oxidative damage to proteins and lipids in cardiac mitochondria from adult (6-month-old), old (15-month-old) and senescent (26-month-old) rats. ETC complexes I-IV displayed different extent of inhibition with age. The most significant decline occurred in complex IV activity, whereas complex II activity was unchanged in old rats and was only slightly reduced in senescent rats. Compared to adult, old and senescent rat hearts had significantly higher levels of malondialdehyde, 4-hydroxynonenal (HNE) and dityrosine, while thiol group content was reduced. Despite marked increase in HNE content with age (25 and 76 % for 15- and 26-month-old rats, respectively) Western blot analysis revealed only few HNE-protein adducts. The present study suggests that non-uniform decline in activities of ETC complexes is due, at least in part, to mitochondrial oxidative damage; however, lipid peroxidation products appear to have a limited impact on enzyme functions.

scholarly journals Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants

2021 ◽  
Author(s):  
Alisha G. Lewis ◽  
Robert Caldwell ◽  
Jason V. Rogers ◽  
Maria Ingaramo ◽  
Rebecca Y. Wang ◽  
...  
Keyword(s):  
Electron Transport ◽  
Signaling Pathways ◽  
Electron Transport Chain ◽  
Nutrient Sensing ◽  
Ph Homeostasis ◽  
Inner Mitochondrial Membrane ◽  
Age Related ◽  
Transport Chain ◽  
Major Nutrient

The electron transport chain (ETC) is a well-studied and highly conserved metabolic pathway that produces ATP through generation of a proton gradient across the inner mitochondrial membrane coupled to oxidative phosphorylation. ETC mutations are associated with a wide array of human disease conditions and to aging-related phenotypes in a number of different organisms. In this study, we sought to better understand the role of the ETC in aging using a yeast model. A panel of ETC mutant strains that fail to survive starvation was used to isolate suppressor mutants that survive. These suppressors tend to fall into major nutrient sensing and signaling pathways, suggesting that the ETC is involved in proper starvation signaling to these pathways in yeast. These suppressors also partially restore ETC-associated gene expression and pH homeostasis defects, though it remains unclear if these phenotypes directly cause the suppression or are simply effects. This work further highlights the complex cellular network connections between metabolic pathways and signaling events in the cell, and their potential roles in aging and age-related diseases.

Nicotinamide adenine dinucleotide (NAD+): essential redox metabolite, co-substrate and an anti-cancer and anti-ageing therapeutic target

2020 ◽  
Vol 48 (3) ◽  
pp. 733-744 ◽  
Author(s):  
Hollie B.S. Griffiths ◽  
Courtney Williams ◽  
Sarah J. King ◽  
Simon J. Allison
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Tumour Microenvironment ◽  
Nicotinamide Adenine ◽  
Reduced Form ◽  
Nad Metabolism ◽  
Growth And Survival ◽  
Cell Functions ◽  
Disease States ◽  
Age Related ◽  
Redox Metabolites

Nicotinamide adenine dinucleotide (NAD+) and its reduced form NADH are essential coupled redox metabolites that primarily promote cellular oxidative (catabolic) metabolic reactions. This enables energy generation through glycolysis and mitochondrial respiration to support cell growth and survival. In addition, many key enzymes that regulate diverse cell functions ranging from gene expression to proteostasis require NAD+ as a co-substrate for their catalytic activity. This includes the NAD+-dependent sirtuin family of protein deacetylases and the PARP family of DNA repair enzymes. Whilst their vital activity consumes NAD+ which is cleaved to nicotinamide, several pathways exist for re-generating NAD+ and sustaining NAD+ homeostasis. However, there is growing evidence of perturbed NAD+ homeostasis and NAD+-regulated processes contributing to multiple disease states. NAD+ levels decline in the human brain and other organs with age and this is associated with neurodegeneration and other age-related diseases. Dietary supplementation with NAD+ precursors is being investigated to counteract this. Paradoxically, many cancers have increased dependency on NAD+. Clinical efforts to exploit this have so far shown limited success. Emerging new opportunities to exploit dysregulation of NAD+ metabolism in cancers are critically discussed. An update is also provided on other key NAD+ research including perturbation of the NAD+ salvage enzyme NAMPT in the context of the tumour microenvironment (TME), methodology to study subcellular NAD+ dynamics in real-time and the regulation of differentiation by competing NAD+ pools.

scholarly journals Implications of NAD+ Metabolism in the Aging Retina and Retinal Degeneration

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ravirajsinh N. Jadeja ◽  
Menaka C. Thounaojam ◽  
Manuela Bartoli ◽  
Pamela M. Martin
Keyword(s):  
Nad Metabolism ◽  
Age Related ◽  
Promising Therapeutic Target ◽  
Organ Systems ◽  
Age Dependent ◽  
The Subject ◽  
Mitochondrial Oxidative Damage ◽  
And Function ◽  
Visual Health

Nicotinamide adenine dinucleotide (NAD+) plays an important role in various key biological processes including energy metabolism, DNA repair, and gene expression. Accumulating clinical and experimental evidence highlights an age-dependent decline in NAD+ levels and its association with the development and progression of several age-related diseases. This supports the establishment of NAD+ as a critical regulator of aging and longevity and, relatedly, a promising therapeutic target to counter adverse events associated with the normal process of aging and/or the development and progression of age-related disease. Relative to the above, the metabolism of NAD+ has been the subject of numerous investigations in various cells, tissues, and organ systems; however, interestingly, studies of NAD+ metabolism in the retina and its relevance to the regulation of visual health and function are comparatively few. This is surprising given the critical causative impact of mitochondrial oxidative damage and bioenergetic crises on the development and progression of degenerative disease of the retina. Hence, the role of NAD+ in this tissue, normally and aging and/or disease, should not be ignored. Herein, we discuss important findings in the field of NAD+ metabolism, with particular emphasis on the importance of the NAD+ biosynthesizing enzyme NAMPT, the related metabolism of NAD+ in the retina, and the consequences of NAMPT and NAD+ deficiency or depletion in this tissue in aging and disease. We discuss also the implications of potential therapeutic strategies that augment NAD+ levels on the preservation of retinal health and function in the above conditions. The overarching goal of this review is to emphasize the importance of NAD+ metabolism in normal, aging, and/or diseased retina and, by so doing, highlight the necessity of additional clinical studies dedicated to evaluating the therapeutic utility of strategies that enhance NAD+ levels in improving vision.

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