Cell-autonomous and non-autonomous roles of daf-16 in muscle function and mitochondrial capacity in aging C. elegans

Hongning Wang, Phillip Webster, Lizhen Chen, Alfred L Fisher

Research output: Contribution to journalArticle

Abstract

Sarcopenia, defined as the loss of skeletal muscle mass and strength, contributes to disability and health-related conditions with aging. In vitro studies indicate that age-related mitochondrial dysfunction could play a central role in the development and progression of sarcopenia, but because of limitations in the methods employed, how aging affects muscle mitochondrial function in vivo is not fully understood. We use muscle-targeted fluorescent proteins and the ratiometric ATP reporter, ATeam, to examine changes in muscle mitochondrial mass and morphology, and intracellular ATP levels in C. elegans. We find that the preserved muscle function in aging daf-2 mutants is associated with higher muscle mitochondrial mass, preserved mitochondrial morphology, and higher levels of intracellular ATP. These phenotypes require the daf-16/FOXO transcription factor. Via the tissue-specific rescue of daf-16, we find that daf-16 activity in either muscle or neurons is sufficient to enhance muscle mitochondrial mass, whereas daf-16 activity in the muscle is required for the enhanced muscle function and mobility of the daf-2 mutants. Finally, we show through the use of drugs known to enhance mitochondrial activity that augmenting mitochondrial function leads to improved mobility during aging. These results suggest an important role for mitochondrial function in muscle aging.

Original languageEnglish (US)
Pages (from-to)2295-2311
Number of pages17
JournalAging
Volume11
Issue number8
DOIs
StatePublished - Apr 30 2019

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Muscles
Sarcopenia
Adenosine Triphosphate
Muscle Strength
Skeletal Muscle
Transcription Factors
Phenotype
Neurons
Health
Pharmaceutical Preparations
Proteins

Keywords

  • Aging
  • Daf-16
  • Daf-2
  • Mitochondria
  • Muscle

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Cell-autonomous and non-autonomous roles of daf-16 in muscle function and mitochondrial capacity in aging C. elegans. / Wang, Hongning; Webster, Phillip; Chen, Lizhen; Fisher, Alfred L.

In: Aging, Vol. 11, No. 8, 30.04.2019, p. 2295-2311.

Research output: Contribution to journalArticle

Wang, Hongning ; Webster, Phillip ; Chen, Lizhen ; Fisher, Alfred L. / Cell-autonomous and non-autonomous roles of daf-16 in muscle function and mitochondrial capacity in aging C. elegans. In: Aging. 2019 ; Vol. 11, No. 8. pp. 2295-2311.
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