Differential Effects of Rapamycin and Metformin in Combination With Rapamycin on Mechanisms of Proteostasis in Cultured Skeletal Myotubes.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Christopher A WolffDanielle R Bruns

Abstract

mTOR inhibition extends life span in multiple organisms. In mice, when metformin treatment (Met) is added to the mTOR inhibitor rapamycin (Rap), median and maximal life span is extended to a greater degree than with Rap or Met alone. Treatments that extend life span often maintain proteostasis. However, it is less clear how individual tissues, such as skeletal muscle, maintain proteostasis with life span-extending treatments. In C2C12 myotubes, we used deuterium oxide (D2O) to directly measure two primary determinants of proteostasis, protein synthesis, and degradation rates, with Rap or Met+Rap treatments. We accounted for the independent effects of cell growth and loss, and isolated the contribution of autophagy and mitochondrial fission to obtain a comprehensive assessment of protein turnover. Compared with control, both Rap and Met+Rap treatments lowered mitochondrial protein synthesis rates (p < .001) and slowed cellular proliferation (p < .01). These changes resulted in greater activation of mechanisms promoting proteostasis for Rap, but not Met+Rap. Compared with control, both Rap and Met+Rap slowed protein breakdown. Autophagy and mitochondrial fission differentially influenced the proteostatic effects of Rap and Met+Ra...Continue Reading

References

Nov 1, 1992·The American Journal of Physiology·M K Hellerstein, R A Neese
Nov 1, 1993·In Vitro Cellular & Developmental Biology. Animal·S OhkumaH Tamura
Mar 8, 2007·PLoS Medicine·Anthony E CivitareseUNKNOWN CALERIE Pennington Team
Apr 25, 2007·Mechanisms of Ageing and Development·Alan R Hipkiss
Dec 15, 2007·Nature Protocols·Robert BuschMarc K Hellerstein
Oct 27, 2010·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Richard A MillerRandy Strong
Aug 5, 2011·Cold Spring Harbor Symposia on Quantitative Biology·N Mizushima
Aug 7, 2012·Biogerontology·Suresh Kumar PoovathingalRudiyanto Gunawan
Oct 30, 2012·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Benjamin F MillerKaryn L Hamilton
Jan 9, 2013·The Journal of Biological Chemistry·Miriam FranginiChiara Rampazzo
Jan 22, 2013·Aging Cell·Elena A MininaPeter V Bozhkov
May 10, 2013·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Joshua C DrakeBenjamin F Miller
May 21, 2013·Molecular and Cellular Endocrinology·Adam R Konopka, K Sreekumaran Nair
Aug 1, 2013·Nature Communications·Alejandro Martin-MontalvoRafael de Cabo
Feb 4, 2014·Experimental Gerontology·Konstantinos Palikaras, Nektarios Tavernarakis
Jun 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Wouter De HaesLiesbet Temmerman
Jun 8, 2014·Methods in Molecular Biology·Elisabet CuyàsJavier A Menendez
Sep 11, 2014·American Journal of Physiology. Endocrinology and Metabolism·Joshua C DrakeBenjamin F Miller
Oct 7, 2014·Ageing Research Reviews·Benjamin F MillerKaryn L Hamilton
Jan 24, 2015·Journal of Applied Physiology·Benjamin F MillerKaryn L Hamilton
Feb 6, 2015·The Journal of Clinical Investigation·Frank MadeoGuido Kroemer
Jun 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Allen C T TengAnthony O Gramolini
Nov 7, 2015·Journal of Diabetes Investigation·Kyu Yeon Hur, Myung-Shik Lee
Nov 18, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael Lynch, Georgi K Marinov
Dec 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jinghui ZhaoAlfred Lewis Goldberg
Jun 29, 2016·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Alan DiotJoanna Poulton
Aug 5, 2017·Diabetologia·Graham RenaEwan R Pearson
Sep 13, 2017·The Journal of Cell Biology·Jonathon L BurmanRichard J Youle
Oct 8, 2017·European Journal of Applied Physiology·Robert V MusciBenjamin F Miller
Jun 2, 2018·Journal of Applied Physiology·Danielle R BrunsKaryn L Hamilton

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Citations

Sep 24, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Dudley W Lamming, Adam B Salmon
Mar 28, 2020·Journal of Applied Physiology·Benjamin F MillerKenneth Smith
Aug 28, 2020·Frontiers in Endocrinology·Steven K Malin, Nathan R Stewart
Feb 2, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Guangli LuChuning Zhang

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