Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy.

The Journal of Biological Chemistry
Scott M EbertChristopher M Adams

Abstract

Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality, and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs repressed by ursolic acid and tomatidine in aged muscle are positively regulated by activating transcription factor 4 (ATF4). Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We fou...Continue Reading

References

Jun 5, 2003·Physiological Genomics·Stephen WelleCharles A Thornton
Mar 24, 2004·Experimental Gerontology·Stephen WelleCharles A Thornton
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 2, 2006·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Bret H GoodpasterAnne B Newman
May 1, 2007·The International Journal of Biochemistry & Cell Biology·Kurosh Ameri, Adrian L Harris
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Tina WenzCarlos T Moraes
Mar 4, 2010·Molecular Endocrinology·Scott M EbertChristopher M Adams
Mar 14, 2012·Cell Biochemistry and Function·Vandré Casagrande Figueiredo, Gustavo A Nader
May 16, 2012·Advances in Nutrition·Thomas D Baird, Ronald C Wek
Jun 14, 2012·The Journal of Biological Chemistry·Scott M EbertChristopher M Adams
Oct 24, 2012·Exercise and Sport Sciences Reviews·Craig A Goodman, Troy A Hornberger
Jun 19, 2013·The International Journal of Biochemistry & Cell Biology·Bradley S GordonScot R Kimball
Jul 19, 2013·The Journal of Clinical Investigation·Frauke NeffDan Ehninger
Jul 23, 2013·Exercise and Sport Sciences Reviews·Jared M DickinsonBlake B Rasmussen
Aug 13, 2013·Age·T M Maden-WilkinsonH Degens
Aug 15, 2013·American Journal of Physiology. Endocrinology and Metabolism·Kale S BongersChristopher M Adams
Oct 5, 2013·Disease Models & Mechanisms·Fabio DemontisNorbert Perrimon
Apr 11, 2014·The Journal of Biological Chemistry·Michael C DyleChristopher M Adams
Jun 5, 2014·American Journal of Physiology. Endocrinology and Metabolism·Daniel K FoxChristopher M Adams
Mar 26, 2015·Current Opinion in Clinical Nutrition and Metabolic Care·Christopher M AdamsMichael C Dyle

❮ Previous
Next ❯

Citations

Dec 9, 2016·Journal of Nutritional Science and Vitaminology·Yuri KusanoWakako Takeuchi
Jun 28, 2016·Domestic Animal Endocrinology·T G Anthony
Apr 5, 2017·Current Opinion in Clinical Nutrition and Metabolic Care·Christopher M AdamsMichael C Dyle
Mar 25, 2018·BMC Neuroscience·Ruping FanNadejda L Korneeva
Feb 2, 2017·American Journal of Physiology. Endocrinology and Metabolism·Colleen S DeanePhilip J Atherton
Jul 7, 2016·American Journal of Physiology. Endocrinology and Metabolism·Philip J AthertonCharles H Lang
Jan 13, 2018·Frontiers in Cellular Neuroscience·Priyamvada M PitaleMarina Gorbatyuk
Aug 2, 2017·Current Medicinal Chemistry·Tyler B WaltzEvandro F Fang
Jun 6, 2019·Physiology·Scott M EbertChristopher M Adams
Sep 16, 2016·EMBO Reports·Karolina Pakos-ZebruckaAdrienne M Gorman
Mar 25, 2020·Medicine and Science in Sports and Exercise·Jaakko HentiläMarko T Korhonen
Nov 21, 2019·Journal of Exercise Nutrition & Biochemistry·Yun Seok KangSang Hyun Kim
Dec 31, 2016·Nutrition and Healthy Aging·Michael E Walsh, Holly Van Remmen
Jul 13, 2017·Scientific Reports·Jessica L CooperstoneTatiana M Oberyszyn
Jul 3, 2018·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Jae Cheol KimSang Hyun Kim
Aug 4, 2020·Annals of Geriatric Medicine and Research·Ju Yeon Kwak, Ki-Sun Kwon
Jun 21, 2018·Cells·Rose GhemrawiCarole Arnold
Aug 30, 2019·Journal of Applied Physiology·Scott M EbertChristopher M Adams
Nov 2, 2019·Journal of Nutritional Science and Vitaminology·Yuri KusanoWakako Takeuchi
Mar 2, 2018·Journal of Nutritional Science and Vitaminology·Miho Chikazawa, Ryuichiro Sato
May 3, 2018·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Dae Yun SeoJin Han
Mar 20, 2020·The Journal of Nutrition·Blake B Rasmussen, Christopher M Adams
Apr 21, 2016·American Journal of Physiology. Endocrinology and Metabolism·Daniel J HamRené Koopman
Jun 21, 2020·Antioxidants·Ekaterina ProshkinaAlexey Moskalev
Dec 2, 2020·Cells·Giorgio AquilaRosanna Piccirillo
Aug 18, 2020·Canadian Journal of Physiology and Pharmacology·Mahavir SinghSuresh C Tyagi
Apr 4, 2021·International Journal of Molecular Sciences·Yann S Gallot, Kyle R Bohnert
May 1, 2021·Pharmaceuticals·Tapan BehlDomenico Montesano
Jul 26, 2021·Molecular Metabolism·Vanessa BylesBrendan D Manning
Nov 2, 2021·Journal of Nutritional Science and Vitaminology·Takanaga ShiraiTohru Takemasa

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
Genotyping

Software Mentioned

MS Solutions
Mouse Ref - 8
LC
CellSens
Empower
BeadStudio

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.