The NAD+/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling
Laurent Mouchiroud,Riekelt H. Houtkooper,Norman Moullan,Elena Katsyuba,Dongryeol Ryu,Carles Cantó,Adrienne Mottis,Young Suk Jo,Mohan Viswanathan,Kristina Schoonjans,Leonard Guarente,Johan Auwerx +11 more
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TLDR
The data suggest that augmenting mitochondrial stress signaling through the modulation of NAD(+) levels may be a target to improve mitochondrial function and prevent or treat age-associated decline.About:
This article is published in Cell.The article was published on 2013-07-18 and is currently open access. It has received 935 citations till now. The article focuses on the topics: SIRT3 & Mitochondrial unfolded protein response.read more
Citations
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Journal ArticleDOI
Declining NAD + Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging
Ana P. Gomes,Ana P. Gomes,Nathan L. Price,Alvin J. Y. Ling,Javid Moslehi,Magdalene K. Montgomery,Luis A. Rajman,James P. White,João S. Teodoro,Christiane D. Wrann,Basil P. Hubbard,Evi M. Mercken,Carlos M. Palmeira,Rafael de Cabo,Anabela P. Rolo,Nigel Turner,Eric L. Bell,David A. Sinclair,David A. Sinclair +18 more
TL;DR: It is shown that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits, and an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age.
Journal ArticleDOI
NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus.
TL;DR: This review summarizes how NAD(+) metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited.
Journal ArticleDOI
The Mitochondrial Basis of Aging
TL;DR: It is suggested that mitochondria influence or regulate a number of key aspects of aging and suggest that strategies directed at improving mitochondrial quality and function might have far-reaching beneficial effects.
Journal ArticleDOI
NAD+ and sirtuins in aging and disease
TL;DR: The combination of sirtuin activation and NAD(+) intermediate supplementation may be an effective antiaging intervention, providing hope to aging societies worldwide.
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NAD+ in aging, metabolism, and neurodegeneration
TL;DR: Factors that regulate NAD+ and how supplementation with NAD+ precursors may represent a new therapeutic opportunity for aging and its associated disorders, particularly neurodegenerative diseases are reviewed.
References
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Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha.
Marie Lagouge,Carmen Argmann,Zachary Gerhart-Hines,Hamid Meziane,Carles Lerin,Frédéric N. Daussin,Nadia Messadeq,Jill C. Milne,Philip D. Lambert,Peter J. Elliott,Bernard Geny,Markku Laakso,Pere Puigserver,Johan Auwerx +13 more
TL;DR: RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in P GC-1alpha acetylation and an increase in PGC-1 alpha activity.
Journal ArticleDOI
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
TL;DR: The analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo, and provides a molecular framework of NAD-dependent histone de acetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.
Journal ArticleDOI
Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase
Anne Brunet,Lora B. Sweeney,J. Fitzhugh Sturgill,Katrin F. Chua,Paul L. Greer,Yingxi Lin,Hien Tran,Sarah E. Ross,Raul Mostoslavsky,Haim Y. Cohen,Linda Hu,Hwei-Ling Cheng,Mark P. Jedrychowski,Steven P. Gygi,David A. Sinclair,Frederick W. Alt,Michael E. Greenberg +16 more
TL;DR: One way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.
Journal ArticleDOI
Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1.
Joseph T. Rodgers,Carlos Lerin,Wilhelm Haas,Steven P. Gygi,Bruce M. Spiegelman,Pere Puigserver +5 more
TL;DR: It is shown that the Sir2 homologue, SIRT1 controls the gluconeogenic/glycolytic pathways in liver in response to fasting signals through the transcriptional coactivator PGC-1α, and this findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan.
Journal ArticleDOI
AMPK regulates energy expenditure by modulating NAD + metabolism and SIRT1 activity
Carles Cantó,Zachary Gerhart-Hines,Jerome N. Feige,Marie Lagouge,Liliana Noriega,Liliana Noriega,Jill C. Milne,Peter J. Elliott,Pere Puigserver,Johan Auwerx,Johan Auwerx +10 more
TL;DR: It is demonstrated that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD+-dependent type III deacetylase SIRT1.
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Declining NAD + Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging
Ana P. Gomes,Ana P. Gomes,Nathan L. Price,Alvin J. Y. Ling,Javid Moslehi,Magdalene K. Montgomery,Luis A. Rajman,James P. White,João S. Teodoro,Christiane D. Wrann,Basil P. Hubbard,Evi M. Mercken,Carlos M. Palmeira,Rafael de Cabo,Anabela P. Rolo,Nigel Turner,Eric L. Bell,David A. Sinclair,David A. Sinclair +18 more