Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

Sarah J. Mitchell; Julio Madrigal-Matute; Morten Scheibye-Knudsen; Evandro Fang; Miguel Aon; José A. González-Reyes; Sonia Cortassa; Susmita Kaushik; Marta Gonzalez-Freire; Bindi Patel; Devin Wahl; Ahmed Ali; Miguel Calvo-Rubio; María I. Burón; Vincent Guiterrez; Theresa M. Ward; Hector H. Palacios; Huan Cai; David W. Frederick; Christopher Hine; Filomena Broeskamp; Lukas Habering; John Dawson; T. Mark Beasley; Junxiang Wan; Yuji Ikeno; Gene Hubbard; Kevin G. Becker; Yongqing Zhang; Vilhelm A. Bohr; Dan L. Longo; Placido Navas; Luigi Ferrucci; David A. Sinclair; Pinchas Cohen; Josephine M. Egan; James R. Mitchell; Joseph A. Baur; David B. Allison; R. Michael Anson; José M. Villalba; Frank Madeo; Ana Maria Cuervo; Kevin J. Pearson; Donald K. Ingram; Michel Bernier; Rafael De Cabo

doi:10.1016/j.cmet.2016.05.027

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

Sarah J. Mitchell, Julio Madrigal-Matute, Morten Scheibye-Knudsen, Evandro Fang, Miguel Aon, José A. González-Reyes, Sonia Cortassa, Susmita Kaushik, Marta Gonzalez-Freire, Bindi Patel, Devin Wahl, Ahmed Ali, Miguel Calvo-Rubio, María I. Burón, Vincent Guiterrez, Theresa M. Ward, Hector H. Palacios, Huan Cai, David W. Frederick, Christopher HineFilomena Broeskamp, Lukas Habering, John Dawson, T. Mark Beasley, Junxiang Wan, Yuji Ikeno, Gene Hubbard, Kevin G. Becker, Yongqing Zhang, Vilhelm A. Bohr, Dan L. Longo, Placido Navas, Luigi Ferrucci, David A. Sinclair, Pinchas Cohen, Josephine M. Egan, James R. Mitchell, Joseph A. Baur, David B. Allison, R. Michael Anson, José M. Villalba, Frank Madeo, Ana Maria Cuervo, Kevin J. Pearson, Donald K. Ingram, Michel Bernier, Rafael De Cabo

School of Medicine

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

174 Scopus citations

Abstract

Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.

Original language	English (US)
Pages (from-to)	1093-1112
Number of pages	20
Journal	Cell Metabolism
Volume	23
Issue number	6
DOIs	https://doi.org/10.1016/j.cmet.2016.05.027
State	Published - Jun 14 2016

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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Mitchell, S. J., Madrigal-Matute, J., Scheibye-Knudsen, M., Fang, E., Aon, M., González-Reyes, J. A., Cortassa, S., Kaushik, S., Gonzalez-Freire, M., Patel, B., Wahl, D., Ali, A., Calvo-Rubio, M., Burón, M. I., Guiterrez, V., Ward, T. M., Palacios, H. H., Cai, H., Frederick, D. W., ... De Cabo, R. (2016). Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell Metabolism, 23(6), 1093-1112. https://doi.org/10.1016/j.cmet.2016.05.027

Mitchell, SJ, Madrigal-Matute, J, Scheibye-Knudsen, M, Fang, E, Aon, M, González-Reyes, JA, Cortassa, S, Kaushik, S, Gonzalez-Freire, M, Patel, B, Wahl, D, Ali, A, Calvo-Rubio, M, Burón, MI, Guiterrez, V, Ward, TM, Palacios, HH, Cai, H, Frederick, DW, Hine, C, Broeskamp, F, Habering, L, Dawson, J, Beasley, TM, Wan, J, Ikeno, Y, Hubbard, G, Becker, KG, Zhang, Y, Bohr, VA, Longo, DL, Navas, P, Ferrucci, L, Sinclair, DA, Cohen, P, Egan, JM, Mitchell, JR, Baur, JA, Allison, DB, Anson, RM, Villalba, JM, Madeo, F, Cuervo, AM, Pearson, KJ, Ingram, DK, Bernier, M & De Cabo, R 2016, 'Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice', Cell Metabolism, vol. 23, no. 6, pp. 1093-1112. https://doi.org/10.1016/j.cmet.2016.05.027

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title = "Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice",

abstract = "Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.",

author = "Mitchell, {Sarah J.} and Julio Madrigal-Matute and Morten Scheibye-Knudsen and Evandro Fang and Miguel Aon and Gonz{\'a}lez-Reyes, {Jos{\'e} A.} and Sonia Cortassa and Susmita Kaushik and Marta Gonzalez-Freire and Bindi Patel and Devin Wahl and Ahmed Ali and Miguel Calvo-Rubio and Bur{\'o}n, {Mar{\'i}a I.} and Vincent Guiterrez and Ward, {Theresa M.} and Palacios, {Hector H.} and Huan Cai and Frederick, {David W.} and Christopher Hine and Filomena Broeskamp and Lukas Habering and John Dawson and Beasley, {T. Mark} and Junxiang Wan and Yuji Ikeno and Gene Hubbard and Becker, {Kevin G.} and Yongqing Zhang and Bohr, {Vilhelm A.} and Longo, {Dan L.} and Placido Navas and Luigi Ferrucci and Sinclair, {David A.} and Pinchas Cohen and Egan, {Josephine M.} and Mitchell, {James R.} and Baur, {Joseph A.} and Allison, {David B.} and Anson, {R. Michael} and Villalba, {Jos{\'e} M.} and Frank Madeo and Cuervo, {Ana Maria} and Pearson, {Kevin J.} and Ingram, {Donald K.} and Michel Bernier and {De Cabo}, Rafael",

note = "Publisher Copyright: {\textcopyright} 2016 Published by Elsevier Inc.",

year = "2016",

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doi = "10.1016/j.cmet.2016.05.027",

language = "English (US)",

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T1 - Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

AU - Mitchell, Sarah J.

AU - Madrigal-Matute, Julio

AU - Scheibye-Knudsen, Morten

AU - Fang, Evandro

AU - Aon, Miguel

AU - González-Reyes, José A.

AU - Cortassa, Sonia

AU - Kaushik, Susmita

AU - Gonzalez-Freire, Marta

AU - Patel, Bindi

AU - Wahl, Devin

AU - Ali, Ahmed

AU - Calvo-Rubio, Miguel

AU - Burón, María I.

AU - Guiterrez, Vincent

AU - Ward, Theresa M.

AU - Palacios, Hector H.

AU - Cai, Huan

AU - Frederick, David W.

AU - Hine, Christopher

AU - Broeskamp, Filomena

AU - Habering, Lukas

AU - Dawson, John

AU - Beasley, T. Mark

AU - Wan, Junxiang

AU - Ikeno, Yuji

AU - Hubbard, Gene

AU - Becker, Kevin G.

AU - Zhang, Yongqing

AU - Bohr, Vilhelm A.

AU - Longo, Dan L.

AU - Navas, Placido

AU - Ferrucci, Luigi

AU - Sinclair, David A.

AU - Cohen, Pinchas

AU - Egan, Josephine M.

AU - Mitchell, James R.

AU - Baur, Joseph A.

AU - Allison, David B.

AU - Anson, R. Michael

AU - Villalba, José M.

AU - Madeo, Frank

AU - Cuervo, Ana Maria

AU - Pearson, Kevin J.

AU - Ingram, Donald K.

AU - Bernier, Michel

AU - De Cabo, Rafael

PY - 2016/6/14

Y1 - 2016/6/14

N2 - Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.

AB - Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.

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DO - 10.1016/j.cmet.2016.05.027

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AN - SCOPUS:84975455180

SN - 1550-4131

VL - 23

SP - 1093

EP - 1112

JO - Cell Metabolism

JF - Cell Metabolism

IS - 6

ER -

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

Abstract

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