Pharmacologic targeting of sirtuin and PPAR signaling improves longevity and mitochondrial physiology in respiratory chain complex I mutant Caenorhabditis elegans

Mitochondrion
Shana McCormackMarni J Falk

Abstract

Mitochondrial respiratory chain (RC) diseases are highly morbid multi-systemic conditions for which few effective therapies exist. Given the essential role of sirtuin and PPAR signaling in mediating both mitochondrial physiology and the cellular response to metabolic stress in RC complex I (CI) disease, we postulated that drugs that alter these signaling pathways either directly (resveratrol for sirtuin, rosiglitazone for PPARγ, fenofibrate for PPARα), or indirectly by increasing NAD(+) availability (nicotinic acid), might offer effective treatment strategies for primary RC disease. Integrated effects of targeting these cellular signaling pathways on animal lifespan and multi-dimensional in vivo parameters were studied in gas-1(fc21) relative to wild-type (N2 Bristol) worms. Specifically, animal lifespan, transcriptome profiles, mitochondrial oxidant burden, mitochondrial membrane potential, mitochondrial content, amino acid profiles, stable isotope-based intermediary metabolic flux, and total nematode NADH and NAD(+) concentrations were compared. Shortened gas-1(fc21) mutant lifespan was rescued with either resveratrol or nicotinic acid, regardless of whether treatments were begun at the early larval stage or in young adulthoo...Continue Reading

References

Mar 30, 2001·The Journal of Biological Chemistry·E B KayserM M Sedensky
Sep 26, 2002·The Journal of Biological Chemistry·Kevin J BittermanDavid A Sinclair
Mar 29, 2005·Neuromuscular Disorders : NMD·Salvatore DiMauro, Michio Hirano
Nov 11, 2005·Mechanisms of Ageing and Development·Yamei Wang, Heidi A Tissenbaum
Nov 18, 2005·The Journal of Biological Chemistry·Simona TodiscoFerdinando Palmieri
Jul 15, 2006·Experimental Gerontology·Arnab MukhopadhyayHeidi A Tissenbaum
Apr 27, 2007·Annals of the New York Academy of Sciences·Jan GruberBarry Halliwell
Jan 8, 2008·Molecular Genetics and Metabolism·M J FalkP G Morgan
Feb 5, 2008·Molecular Genetics and Metabolism·UNKNOWN Mitochondrial Medicine Society's Committee on DiagnosisRobert K Naviaux
Aug 19, 2009·Annals of the New York Academy of Sciences·Eric L GreerAnne Brunet
Oct 24, 2009·PloS One·Juliette Ben ArousDidier Chatenay
Dec 17, 2009·Endocrine Reviews·Riekelt H HoutkooperJohan Auwerx
May 11, 2010·Archives of Biochemistry and Biophysics·Sangwoon ChungIrfan Rahman
Jun 24, 2010·Antioxidants & Redox Signaling·Jeremy Michael Van Raamsdonk, Siegfried Hekimi
Oct 20, 2010·The Journal of Biological Chemistry·Michael Schupp, Mitchell A Lazar
Nov 17, 2010·Biochemical and Biophysical Research Communications·Joo-Man ParkYong-Ho Ahn
Mar 16, 2011·Journal of Visualized Experiments : JoVE·Marni J FalkMarc Yudkoff
Apr 5, 2011·Cell Metabolism·Péter BaiJohan Auwerx
May 14, 2011·EMBO Molecular Medicine·Marni J FalkDavid L Gasser
Mar 8, 2012·Nature Reviews. Molecular Cell Biology·Riekelt H HoutkooperJohan Auwerx
Jan 15, 2013·Mechanisms of Ageing and Development·Harald FrankowskiH Michael Ellerby
Mar 9, 2013·Science·Basil P HubbardDavid A Sinclair
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Andreas H LudewigFrank C Schroeder
Nov 2, 2013·The Journal of Biological Chemistry·Valérie Desquiret-DumasVincent Procaccio
Dec 5, 2013·Nature Communications·M D NelsonD M Raizen
Apr 9, 2014·EMBO Molecular Medicine·Nahid A KhanAnu Suomalainen

❮ Previous
Next ❯

Citations

Jan 5, 2016·Molecular Genetics and Metabolism·Mike GerardsHubert J M Smeets
Jul 21, 2015·Biochimica Et Biophysica Acta·Autumn TocchiPeter S Rabinovitch
Oct 27, 2016·Molecular Genetics and Metabolism·Kathryn M CampPaul M Coates
May 10, 2017·Proceedings of the National Academy of Sciences of the United States of America·Michele FerrariWarren M Zapol
Sep 29, 2019·Canadian Journal of Physiology and Pharmacology·Nontobeko M GumedeEliton Chivandi
Oct 22, 2016·Journal of Inherited Metabolic Disease·Young Joon KwonMichael J Bennett
Nov 4, 2017·Annual Review of Pathology·Adam J KuszakZarazuela Zolkipli-Cunningham
Jun 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Piotr K KopinskiDouglas C Wallace
Sep 7, 2018·Frontiers in Endocrinology·Xinran MaLingyan Xu
Oct 27, 2020·Current Opinion in Pediatrics·Isabella BarcelosMarni J Falk
Feb 29, 2020·Ageing Research Reviews·Marta Gonzalez-FreireRafael de Cabo
Apr 6, 2021·Current HIV/AIDS Reports·Kristine M Erlandson, Damani A Piggott
Aug 8, 2021·Mitochondrion·Raviprasad KuthethurKapaettu Satyamoorthy
Jul 25, 2017·Neurochemistry International·James ByrnesMarni J Falk

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.