The effects of graded levels of calorie restriction

XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome

Davina Derous, Sharon E Mitchell, Lu Wang, Cara L Green, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman

Research output: Contribution to journalArticle

6 Citations (Scopus)
20 Downloads (Pure)

Abstract

Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan. However, the expression levels of SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent with altered fuel utilization under CR may reduce reactive oxygen species production, which was paralleled by reduced protection. Downregulated major urinary protein (MUP) transcription suggested reduced reproductive investment. Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was protective with respect to cancer signaling. CR had no significant effect on fibroblast growth factor-21 (FGF21) transcription but affected transcription in the hydrogen sulfide production pathway. Responses to CR were consistent with several different hypotheses, and the benefits of CR on lifespan likely reflect the combined impact on multiple aging related processes.

Original languageEnglish
Pages (from-to)1770-1824
Number of pages55
JournalAging
Volume9
Issue number7
DOIs
Publication statusPublished - 31 Jul 2017

Fingerprint

Sirtuins
Life Expectancy
Transcriptome
NFI Transcription Factors
Hydrogen Sulfide
Liver
Autophagy
Somatomedins
Xenobiotics
Sirolimus
Inbred C57BL Mouse
Reactive Oxygen Species
Down-Regulation
Insulin
Neoplasms

Keywords

  • aging
  • Calorie restriction
  • Gene Expression
  • liver
  • Transcriptomics

Cite this

The effects of graded levels of calorie restriction : XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome. / Derous, Davina; Mitchell, Sharon E; Wang, Lu; Green, Cara L; Wang, Yingchun; Chen, Luonan; Han, Jing-Dong J; Promislow, Daniel E L; Lusseau, David; Douglas, Alex; Speakman, John R.

In: Aging, Vol. 9, No. 7, 31.07.2017, p. 1770-1824.

Research output: Contribution to journalArticle

@article{913a679c4ccf416b861a8d1e5c52a6b1,
title = "The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome",
abstract = "Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0{\%} to 40{\%} CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan. However, the expression levels of SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent with altered fuel utilization under CR may reduce reactive oxygen species production, which was paralleled by reduced protection. Downregulated major urinary protein (MUP) transcription suggested reduced reproductive investment. Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was protective with respect to cancer signaling. CR had no significant effect on fibroblast growth factor-21 (FGF21) transcription but affected transcription in the hydrogen sulfide production pathway. Responses to CR were consistent with several different hypotheses, and the benefits of CR on lifespan likely reflect the combined impact on multiple aging related processes.",
keywords = "aging, Calorie restriction, Gene Expression, liver, Transcriptomics",
author = "Davina Derous and Mitchell, {Sharon E} and Lu Wang and Green, {Cara L} and Yingchun Wang and Luonan Chen and Han, {Jing-Dong J} and Promislow, {Daniel E L} and David Lusseau and Alex Douglas and Speakman, {John R}",
note = "We would like to acknowledge the BSU staff for their invaluable help with caring for the animals.",
year = "2017",
month = "7",
day = "31",
doi = "10.18632/aging.101269",
language = "English",
volume = "9",
pages = "1770--1824",
journal = "Aging",
issn = "1945-4589",
publisher = "IMPACT JOURNALS LLC",
number = "7",

}

TY - JOUR

T1 - The effects of graded levels of calorie restriction

T2 - XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome

AU - Derous, Davina

AU - Mitchell, Sharon E

AU - Wang, Lu

AU - Green, Cara L

AU - Wang, Yingchun

AU - Chen, Luonan

AU - Han, Jing-Dong J

AU - Promislow, Daniel E L

AU - Lusseau, David

AU - Douglas, Alex

AU - Speakman, John R

N1 - We would like to acknowledge the BSU staff for their invaluable help with caring for the animals.

PY - 2017/7/31

Y1 - 2017/7/31

N2 - Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan. However, the expression levels of SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent with altered fuel utilization under CR may reduce reactive oxygen species production, which was paralleled by reduced protection. Downregulated major urinary protein (MUP) transcription suggested reduced reproductive investment. Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was protective with respect to cancer signaling. CR had no significant effect on fibroblast growth factor-21 (FGF21) transcription but affected transcription in the hydrogen sulfide production pathway. Responses to CR were consistent with several different hypotheses, and the benefits of CR on lifespan likely reflect the combined impact on multiple aging related processes.

AB - Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan. However, the expression levels of SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent with altered fuel utilization under CR may reduce reactive oxygen species production, which was paralleled by reduced protection. Downregulated major urinary protein (MUP) transcription suggested reduced reproductive investment. Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was protective with respect to cancer signaling. CR had no significant effect on fibroblast growth factor-21 (FGF21) transcription but affected transcription in the hydrogen sulfide production pathway. Responses to CR were consistent with several different hypotheses, and the benefits of CR on lifespan likely reflect the combined impact on multiple aging related processes.

KW - aging

KW - Calorie restriction

KW - Gene Expression

KW - liver

KW - Transcriptomics

U2 - 10.18632/aging.101269

DO - 10.18632/aging.101269

M3 - Article

VL - 9

SP - 1770

EP - 1824

JO - Aging

JF - Aging

SN - 1945-4589

IS - 7

ER -