NADH Reductive Stress and Its Correlation with Disease Severity in Leigh Syndrome: A Pilot Study Using Patient Fibroblasts and a Mouse Model DOI Creative Commons
Tamaki Ishima,

Natsuka Kimura,

Mizuki Kobayashi

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 15(1), P. 38 - 38

Published: Dec. 31, 2024

Nicotinamide adenine dinucleotide (NAD) is a critical cofactor in mitochondrial energy production. The NADH/NAD+ ratio, reflecting the balance between NADH (reduced) and NAD+ (oxidized), key marker for severity of diseases. We recently developed streamlined LC-MS/MS method precise measurement NAD+. Utilizing this technique, we quantified levels fibroblasts derived from pediatric patients Leigh syndrome mouse model which respiratory chain complex I subunit Ndufs4 knocked out (KO). In patient-derived fibroblasts, did not differ significantly those healthy controls (p = 0.79); however, were elevated 0.04), indicating increased reductive stress. This increase, observed despite comparable total NAD(H) groups, was attributed to levels. Similarly, model, KO group 0.002), further suggesting that elevation drives expected outperform conventional assays, such as lactate, providing simpler more reliable means assessing disease progression.

Language: Английский

Regulation of and challenges in targeting NAD+ metabolism DOI
Marie E. Migaud, Mathias Ziegler, Joseph A. Baur

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(10), P. 822 - 840

Published: July 18, 2024

Language: Английский

Citations

13

Reproductive Ageing: Current insights and a potential role of NAD in the reproductive health of aging fathers and their children DOI

Morgan B. Feuz,

Darin Nelson,

Laura B. Miller

et al.

Reproduction, Journal Year: 2024, Volume and Issue: 167(6)

Published: March 12, 2024

In light of the increasing age first-time fathers, this article summarizes current scientific knowledge base on reproductive aging in male, including sperm quality and health impacts for offspring. The emerging role NAD decline is highlighted.

Language: Английский

Citations

4

OAB-14 alleviates mitochondrial impairment through the SIRT3-dependent mechanism in APP/PS1 transgenic mice and N2a/APP cells DOI
Na Zheng,

Ruo-lin Cao,

Danyang Liu

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0

Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation DOI Creative Commons
Sofie Lautrup, Shiqi Zhang,

Shinichiro Funayama

et al.

Aging, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Werner syndrome (WS), caused by mutations in the RecQ helicase WERNER (WRN) gene, is a classical accelerated aging disease with patients suffering from several metabolic dysfunctions without cure. While, as we previously reported, depleted NAD+ causes accumulation of damaged mitochondria, leading to compromised metabolism, how mitochondrial changes WS and impact on pathologies were unknown. We show that loss WRN increases senescence mesenchymal stem cells (MSCs) likely related dysregulation pathways. In line this, augmentation, via supplementation nicotinamide riboside, reduces improves profiles MSCs knockout (WRN-/-) primary fibroblasts derived compared controls. Moreover, deficiency results decreased (measured indirectly mitochondrially-expressed PARP activity), altered expression key salvage pathway enzymes, including NMNAT1 NAMPT; ChIP-seq data analysis unveils potential co-regulatory axis between NMNATs, important for chromatin stability DNA metabolism. However, restoration or cellular not sufficient reinstall proliferation immortalized siRNA-mediated knockdown WRN, highlighting an indispensable role even affluent environment. Further cell animal studies are needed deepen our understanding underlying mechanisms, facilitating drug development.

Language: Английский

Citations

0

Subcellular NAD+ pools are interconnected and buffered by mitochondrial NAD+ DOI
Lena Elise Høyland,

Magali R. VanLinden,

Marc Niere

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(12), P. 2319 - 2337

Published: Dec. 13, 2024

Language: Английский

Citations

3

Fast and quantitative mitophagy assessment by flow cytometry using the mito-QC reporter DOI Creative Commons
Juan Ignacio Jiménez‐Loygorri,

Carlos Jiménez-García,

Álvaro Viedma-Poyatos

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 11, 2024

Mitochondrial quality control is finely tuned by mitophagy, the selective degradation of mitochondria through autophagy, and mitochondrial biogenesis. Removal damaged essential to preserve cellular bioenergetics prevent detrimental events such as sustained mitoROS production, pro-apoptotic cytochrome c release or mtDNA leakage. The array tools available study mitophagy very limited but in constant development. Almost a decade ago, we developed method assess flux using MitoTracker Deep Red combination with lysosomal inhibitors. Now, novel tandem-fluorescence reporter

Language: Английский

Citations

2

Senolytika und Senomorphika im Kampf gegen neurodegenerative Erkrankungen DOI
Uwe Gröber,

Hans-Peter Friedrichsen

Zeitschrift für Komplementärmedizin, Journal Year: 2024, Volume and Issue: 16(04), P. 28 - 33

Published: July 1, 2024

Summary In der Pathobiochemie von Neurodegeneration und Seneszenz spielen genomische Instabilität, Verkürzung Telomere, epigenetische Mechanismen sowie reaktive Sauerstoff- Stickstoffspezies eine zentrale Rolle. Seneszente Zellen sind charakteristisch für die Alterung. Sie regulieren antiapoptotische Signalwege verhindern so Absterben Elimination mit Läsionen an DNA Zellorganellen. Altersforschung stehen Senolytika im Mittelpunkt, Apoptose oder Lyse seneszenter induzieren zudem neuroprotektiv wirken. Das senolytischeFlavonolFisetin kommt in verschiedenen Obst- Gemüsesorten vor kann seit 1904 synthetisiert werden. Es schützt Nervenzellen Neurotoxizität, Inflammation apoptotischer Degeneration; Wirkung muss noch durch weitere Studien belegt Auch Senomorphika wie Metformin werden zur Unterdrückung eingesetzt.

Citations

1

Mechanisms of the NAD+ salvage pathway in enhancing skeletal muscle function DOI Creative Commons

Mengzhu Su,

Fanghui Qiu,

Yansong Li

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 20, 2024

Nicotinamide adenine dinucleotide (NAD + ) is crucial for cellular energy production, serving as a coenzyme in oxidation-reduction reactions. It also supports enzymes involved processes such DNA repair, aging, and immune responses. Lower NAD levels have been associated with various diseases, highlighting the importance of replenishing NAD+. phosphoribosyltransferase (NAMPT) plays critical role salvage pathway, which helps sustain levels, particularly high-energy tissues like skeletal muscle.This review explores how NAMPT-driven pathway influences muscle health functionality type 2 diabetes mellitus (T2DM), injury. The offers insights into enhancing through exercise boosters strategies to improve performance. findings suggest significant potential using this diagnosis, monitoring, treatment conditions.

Language: Английский

Citations

1

Kidney development at a glance: metabolic regulation of renal progenitor cells DOI
Kristen Kurtzeborn, Samir S. El‐Dahr, Niklas Pakkasjärvi

et al.

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

1

Geroscience and Its Promise DOI
S. Jay Olshansky, James L. Kirkland

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2024, Volume and Issue: 14(8), P. a041725 - a041725

Published: April 2, 2024

S. Jay Olshansky1 and James L. Kirkland2 1School of Public Health, University Illinois at Chicago, 60612, USA 2Department Physiology Biomedical Engineering, Division General Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, Correspondence: sjayo{at}uic.edu; kirkland.james{at}mayo.edu

Language: Английский

Citations

0