Journal ArticleDOI
Muscle wasting in disease: molecular mechanisms and promising therapies
TLDR
Major advances in the understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting.Abstract:
Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries). Muscle wasting occurs systemically in older people (a condition known as sarcopenia); as a physiological response to fasting or malnutrition; and in many diseases, including chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal failure, cardiac failure, Cushing syndrome, sepsis, burns and trauma. The rapid loss of muscle mass and strength primarily results from excessive protein breakdown, which is often accompanied by reduced protein synthesis. This loss of muscle function can lead to reduced quality of life, increased morbidity and mortality. Exercise is the only accepted approach to prevent or slow atrophy. However, several promising therapeutic agents are in development, and major advances in our understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting. Here, we discuss these new insights and the rationally designed therapies that are emerging to combat muscle wasting.read more
Citations
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Nrf2-Keap1 signaling in oxidative and reductive stress.
TL;DR: The effects of the Nrf2-Keap1 system in the physiology and pathophysiology of striated muscle tissue taking into account its role(s) in oxidative stress and reductive stress are highlighted.
Journal ArticleDOI
The extracellular matrix protein agrin promotes heart regeneration in mice
Elad Bassat,Yara Eid Mutlak,Alex Genzelinakh,Ilya Y. Shadrin,Kfir Baruch Umansky,Oren Yifa,David Kain,Dana Rajchman,John Leach,Daria Riabov Bassat,Yael Udi,Rachel Sarig,Irit Sagi,James F. Martin,Nenad Bursac,Shenhav Cohen,Eldad Tzahor +16 more
TL;DR: In vivo, a single administration of agrin promotes cardiac regeneration in adult mice after myocardial infarction, although the degree of cardiomyocyte proliferation observed in this model suggests that there are additional therapeutic mechanisms.
Journal ArticleDOI
Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms
Frank W. Booth,Christian K. Roberts,John P. Thyfault,Gregory N. Ruegsegger,Ryan G. Toedebusch +4 more
TL;DR: It is proposed that physical inactivity could be considered a behavior selected by evolution for resting, and also selected to be reinforcing in life-threatening situations in which exercise would be dangerous.
Journal ArticleDOI
Understanding cachexia as a cancer metabolism syndrome
TL;DR: In specific tumor types, such as pancreatic cancers, it is now clear that patients present markers of tissue wasting at a stage in which tumor is not yet clinically detectable, and that host amino acid supply is required for tumor growth.
Journal ArticleDOI
mTOR inhibition activates overall protein degradation by the ubiquitin proteasome system as well as by autophagy
TL;DR: It is shown that inhibiting mTOR with rapamycin or Torin1 rapidly increases the degradation of long-lived cell proteins, but not short-lived ones, by stimulating proteolysis by proteasomes, in addition to autophagy.
References
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Journal ArticleDOI
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010
Rafael Lozano,Mohsen Naghavi,Kyle J Foreman,Stephen S Lim,Kenji Shibuya,Victor Aboyans,Jerry Abraham,Tim Adair,Rakesh Aggarwal,Stephanie Y. Ahn,Mohammad A. AlMazroa,Miriam Alvarado,H. Ross Anderson,Laurie M. Anderson,Kathryn G. Andrews,Charles Atkinson,Larry M. Baddour,Suzanne Barker-Collo,David Bartels,Michelle L. Bell,Emelia J. Benjamin,Derrick A Bennett,Kavi Bhalla,Boris Bikbov,Aref A. Bin Abdulhak,Gretchen L. Birbeck,Fiona M. Blyth,Ian Bolliger,Soufiane Boufous,Chiara Bucello,Michael Burch,Peter Burney,Jonathan R. Carapetis,Honglei Chen,David Chou,Sumeet S. Chugh,Luc E. Coffeng,Steven D. Colan,Samantha M. Colquhoun,K. Ellicott Colson,John R. Condon,Myles Connor,Myles Connor,Leslie T. Cooper,Matthew A. Corriere,Monica Cortinovis,Karen Courville De Vaccaro,William G. Couser,Benjamin C Cowie,Michael H. Criqui,Marita Cross,Kaustubh Dabhadkar,Nabila Dahodwala,Diego De Leo,Louisa Degenhardt,Allyne Delossantos,Julie O. Denenberg,Don C. Des Jarlais,Samath D Dharmaratne,Samath D Dharmaratne,E. Ray Dorsey,Tim Driscoll,Herbert C. Duber,Beth E. Ebel,Patricia J. Erwin,Patricia Espindola,Majid Ezzati,Valery L. Feigin,Abraham D. Flaxman,Mohammad H. Forouzanfar,F.G.R. Fowkes,Richard C. Franklin,Marlene Fransen,Michael Freeman,Sherine E. Gabriel,Emmanuela Gakidou,Flavio Gaspari,Richard F. Gillum,Diego Gonzalez-Medina,Yara A. Halasa,Diana Haring,James Harrison,Rasmus Havmoeller,Rasmus Havmoeller,Roderick J. Hay,Bruno Hoen,Peter J. Hotez,Damian G Hoy,Kathryn H. Jacobsen,Spencer L. James,Rashmi Jasrasaria,Sudha Jayaraman,Nicole E. Johns,Ganesan Karthikeyan,Nicholas J Kassebaum,Andre Keren,Jon Paul Khoo,Lisa M. Knowlton,Olive Kobusingye,Adofo Koranteng,Rita Krishnamurthi,Michael S Lipnick,Steven E. Lipshultz,Summer Lockett Ohno,Jacqueline Mabweijano,Jacqueline Mabweijano,Michael F. Macintyre,Leslie Mallinger,Lyn March,Guy B. Marks,Robin Marks,Akira Matsumori,Richard Matzopoulos,Richard Matzopoulos,Bongani M. Mayosi,John H. McAnulty,Mary M. McDermott,John J. McGrath,Ziad A. Memish,George A. Mensah,Tony R. Merriman,Catherine Michaud,Matthew J. Miller,Ted R. Miller,Charles Mock,Ana Olga Mocumbi,Ali A. Mokdad,Andrew E. Moran,Kim Mulholland,M. Nathan Nair,Luigi Naldi,K.M. Venkat Narayan,Kiumarss Nasseri,Paul Norman,Martin O'Donnell,Saad B. Omer,Katrina F Ortblad,Richard H. Osborne,Doruk Ozgediz,Bishnu Pahari,Jeyaraj D Pandian,Andrea Panozo Rivero,Rogelio Perez Padilla,Fernando Perez-Ruiz,Norberto Perico,David Phillips,Kelsey Pierce,C. Arden Pope,Esteban Porrini,Farshad Pourmalek,Murugesan Raju,Dharani Ranganathan,Jürgen Rehm,David B. Rein,G. Remuzzi,Frederick P. Rivara,Thomas Roberts,Felipe Rodriguez De Leòn,Lisa C. Rosenfeld,Lesley Rushton,Ralph L. Sacco,Joshua A. Salomon,Uchechukwu Sampson,Ella Sanman,David C. Schwebel,Maria Segui-Gomez,Donald S. Shepard,David Singh,Jessica Singleton,Karen Sliwa,Emma Smith,Andrew C Steer,Jennifer A. Taylor,Bernadette Thomas,Imad M. Tleyjeh,Jeffrey A. Towbin,Thomas Truelsen,Eduardo A. Undurraga,Narayanaswamy Venketasubramanian,Lakshmi Vijayakumar,Theo Vos,Gregory R. Wagner,Mengru Wang,Wenzhi Wang,Kerrianne Watt,Martin A. Weinstock,Robert G. Weintraub,James D. Wilkinson,Anthony D. Woolf,Sarah Wulf,Pon Hsiu Yeh,Paul S. F. Yip,Azadeh Zabetian,Zhi Jie Zheng,Alan D. Lopez,Christopher J L Murray +195 more
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
Journal ArticleDOI
Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member.
TL;DR: Results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth, which is significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass.
Journal ArticleDOI
Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy
Sue C. Bodine,Esther Latres,Susanne Baumhueter,Venus Lai,Lorna Nunez,Brian A. Clarke,William Poueymirou,Frank J. Panaro,Erqian Na,Kumar Dharmarajan,Zhen-Qiang Pan,David M. Valenzuela,Thomas M. DeChiara,Trevor Stitt,George D. Yancopoulos,David J. Glass +15 more
TL;DR: Two genes encode ubiquitin ligases that are potential drug targets for the treatment of muscle atrophy, and mice deficient in either MAFbx orMuRF1 were found to be resistant to atrophy.
Journal ArticleDOI
Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy
Marco Sandri,Claudia Sandri,Alexander Gilbert,Carsten Skurk,Elisa Calabria,Anne Picard,Kenneth Walsh,Stefano Schiaffino,Stewart H. Lecker,Alfred L. Goldberg +9 more
TL;DR: It is shown that in cultured myotubes undergoing atrophy, the activity of the PI3K/AKT pathway decreases, leading to activation of Foxo transcription factors and atrogin-1 induction.
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