Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women

Melissa M. Markofski; Jared M. Dickinson; Micah J. Drummond; Christopher S. Fry; Satoshi Fujita; David M. Gundermann; Erin L. Glynn; Kristofer Jennings; Douglas Paddon-Jones; Paul T. Reidy; Melinda Sheffield-Moore; Kyle L. Timmerman; Blake B. Rasmussen; Elena Volpi

doi:10.1016/j.exger.2015.02.015

Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women

Melissa M. Markofski, Jared M. Dickinson, Micah J. Drummond, Christopher S. Fry, Satoshi Fujita, David M. Gundermann, Erin L. Glynn, Kristofer Jennings, Douglas Paddon-Jones, Paul T. Reidy, Melinda Sheffield-Moore, Kyle L. Timmerman, Blake B. Rasmussen, Elena Volpi

Athletic Training and Clinical Nutrition

Research output: Contribution to journal › Article › peer-review

93 Citations (SciVal)

Abstract

The rate of muscle loss with aging is higher in men than women. However, women have smaller muscles throughout the adult life. Protein content is a major determinant of skeletal muscle size. This study was designed to determine if age and sex differentially impact basal muscle protein synthesis and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling. We performed a secondary data analysis on a cohort of 215 healthy, non-obese (BMI<30kg·m^-2) young (18-40y; 74 men, 52 women) and older (60-87y; 57 men, 32 women) adults. The database contained information on physical characteristics, basal muscle protein fractional synthetic rate (FSR; n=215; stable isotope methodology) and mTORC1 signaling (n=125, Western blotting). FSR and mTORC1 signaling were measured at rest and after an overnight fast. mTORC1 and S6K1 phosphorylation were higher (p<0.05) in older subjects with no sex differences. However, there were no age or sex differences or interaction for muscle FSR (p>0.05). Body mass index, fat free mass, or body fat was not a significant covariate and did not influence the results. We conclude that age and sex do not influence basal muscle protein synthesis. However, basal mTORC1 hyperphosphorylation in the elderly may contribute to insulin resistance and the age-related anabolic resistance of skeletal muscle protein metabolism to nutrition and exercise.

Original language	English
Pages (from-to)	1-7
Number of pages	7
Journal	Experimental Gerontology
Volume	65
DOIs	https://doi.org/10.1016/j.exger.2015.02.015
State	Published - May 1 2015

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health ( National Institute on Aging R01 AG030070 , R01 AG030070S1 , R01 AG018311 , and P30 AG024832 ; National Institute of Arthritis and Musculoskeletal and Skin Diseases R01 AR049877 ; National Institute of Child Health and Human Development T32 HD07539 ; and National Center for Advancing Translational Sciences UL1TR000071 ).

Publisher Copyright:
© 2015 .

Keywords

Aging
Gender
MTOR
Protein metabolism
Sarcopenia
Stable isotopes

ASJC Scopus subject areas

Biochemistry
Aging
Molecular Biology
Genetics
Endocrinology
Cell Biology

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10.1016/j.exger.2015.02.015

Cite this

Markofski, M. M., Dickinson, J. M., Drummond, M. J., Fry, C. S., Fujita, S., Gundermann, D. M., Glynn, E. L., Jennings, K., Paddon-Jones, D., Reidy, P. T., Sheffield-Moore, M., Timmerman, K. L., Rasmussen, B. B., & Volpi, E. (2015). Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women. Experimental Gerontology, 65, 1-7. https://doi.org/10.1016/j.exger.2015.02.015

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title = "Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women",

abstract = "The rate of muscle loss with aging is higher in men than women. However, women have smaller muscles throughout the adult life. Protein content is a major determinant of skeletal muscle size. This study was designed to determine if age and sex differentially impact basal muscle protein synthesis and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling. We performed a secondary data analysis on a cohort of 215 healthy, non-obese (BMI<30kg·m-2) young (18-40y; 74 men, 52 women) and older (60-87y; 57 men, 32 women) adults. The database contained information on physical characteristics, basal muscle protein fractional synthetic rate (FSR; n=215; stable isotope methodology) and mTORC1 signaling (n=125, Western blotting). FSR and mTORC1 signaling were measured at rest and after an overnight fast. mTORC1 and S6K1 phosphorylation were higher (p<0.05) in older subjects with no sex differences. However, there were no age or sex differences or interaction for muscle FSR (p>0.05). Body mass index, fat free mass, or body fat was not a significant covariate and did not influence the results. We conclude that age and sex do not influence basal muscle protein synthesis. However, basal mTORC1 hyperphosphorylation in the elderly may contribute to insulin resistance and the age-related anabolic resistance of skeletal muscle protein metabolism to nutrition and exercise.",

keywords = "Aging, Gender, MTOR, Protein metabolism, Sarcopenia, Stable isotopes",

author = "Markofski, {Melissa M.} and Dickinson, {Jared M.} and Drummond, {Micah J.} and Fry, {Christopher S.} and Satoshi Fujita and Gundermann, {David M.} and Glynn, {Erin L.} and Kristofer Jennings and Douglas Paddon-Jones and Reidy, {Paul T.} and Melinda Sheffield-Moore and Timmerman, {Kyle L.} and Rasmussen, {Blake B.} and Elena Volpi",

note = "Funding Information: This work was supported by the National Institutes of Health ( National Institute on Aging R01 AG030070 , R01 AG030070S1 , R01 AG018311 , and P30 AG024832 ; National Institute of Arthritis and Musculoskeletal and Skin Diseases R01 AR049877 ; National Institute of Child Health and Human Development T32 HD07539 ; and National Center for Advancing Translational Sciences UL1TR000071 ). Publisher Copyright: {\textcopyright} 2015 .",

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Markofski, MM, Dickinson, JM, Drummond, MJ, Fry, CS, Fujita, S, Gundermann, DM, Glynn, EL, Jennings, K, Paddon-Jones, D, Reidy, PT, Sheffield-Moore, M, Timmerman, KL, Rasmussen, BB & Volpi, E 2015, 'Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women', Experimental Gerontology, vol. 65, pp. 1-7. https://doi.org/10.1016/j.exger.2015.02.015

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AU - Markofski, Melissa M.

AU - Dickinson, Jared M.

AU - Drummond, Micah J.

AU - Fry, Christopher S.

AU - Fujita, Satoshi

AU - Gundermann, David M.

AU - Glynn, Erin L.

AU - Jennings, Kristofer

AU - Paddon-Jones, Douglas

AU - Reidy, Paul T.

AU - Sheffield-Moore, Melinda

AU - Timmerman, Kyle L.

AU - Rasmussen, Blake B.

AU - Volpi, Elena

N1 - Funding Information: This work was supported by the National Institutes of Health ( National Institute on Aging R01 AG030070 , R01 AG030070S1 , R01 AG018311 , and P30 AG024832 ; National Institute of Arthritis and Musculoskeletal and Skin Diseases R01 AR049877 ; National Institute of Child Health and Human Development T32 HD07539 ; and National Center for Advancing Translational Sciences UL1TR000071 ). Publisher Copyright: © 2015 .

PY - 2015/5/1

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N2 - The rate of muscle loss with aging is higher in men than women. However, women have smaller muscles throughout the adult life. Protein content is a major determinant of skeletal muscle size. This study was designed to determine if age and sex differentially impact basal muscle protein synthesis and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling. We performed a secondary data analysis on a cohort of 215 healthy, non-obese (BMI<30kg·m-2) young (18-40y; 74 men, 52 women) and older (60-87y; 57 men, 32 women) adults. The database contained information on physical characteristics, basal muscle protein fractional synthetic rate (FSR; n=215; stable isotope methodology) and mTORC1 signaling (n=125, Western blotting). FSR and mTORC1 signaling were measured at rest and after an overnight fast. mTORC1 and S6K1 phosphorylation were higher (p<0.05) in older subjects with no sex differences. However, there were no age or sex differences or interaction for muscle FSR (p>0.05). Body mass index, fat free mass, or body fat was not a significant covariate and did not influence the results. We conclude that age and sex do not influence basal muscle protein synthesis. However, basal mTORC1 hyperphosphorylation in the elderly may contribute to insulin resistance and the age-related anabolic resistance of skeletal muscle protein metabolism to nutrition and exercise.

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KW - Aging

KW - Gender

KW - MTOR

KW - Protein metabolism

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KW - Stable isotopes

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Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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