Age-related phasic patterns of mitochondrial maintenance in adult Caenorhabditis elegans neurons

Natalia S. Morsci, David H. Hall, Monica Driscoll, Zu Hang Sheng

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Aging is associated with cognitive decline and increasing risk of neurodegeneration. Perturbation of mitochondrial function, dynamics, and trafficking are implicated in the pathogenesis of several age-associated neurodegenerative diseases. Despite this fundamental importance, the critical understanding of how organismal aging affects lifetime neuronal mitochondrial maintenance remains unknown, particularly in a physiologically relevant context. To address this issue, we performed a comprehensive in vivo analysis of age-associated changes in mitochondrial morphology, density, trafficking, and stress resistance in individual Caenorhabditis elegans neurons throughout adult life. Adult neurons display three distinct stages of increase, maintenance, and decrease in mitochondrial size and density during adulthood. Mitochondrial trafficking in the distal neuronal processes declines progressively with age starting from early adulthood. In contrast, long-lived daf-2 mutants exhibit delayed age-associated changes in mitochondrial morphology, constant mitochondrial density, and maintained trafficking rates during adulthood. Reduced mitochondrial load at late adulthood correlates with decreased mitochondrial resistance to oxidative stress. Revealing aging-associated changes in neuronal mitochondria in vivo is an essential precedent that will allow future elucidation of the mechanistic causes of mitochondrial aging. Thus, our study establishes the critical foundation for the future analysis of cellular pathways and genetic and pharmacological factors regulating mitochondrial maintenance in aging- and disease-relevant conditions.

Original languageEnglish (US)
Pages (from-to)1373-1385
Number of pages13
JournalJournal of Neuroscience
Volume36
Issue number4
DOIs
StatePublished - Jan 27 2016

Keywords

  • Age-related changes
  • Caenorhabditis elegans
  • In vivo microscopy
  • Mitochondrial trafficking
  • Neuronal mitochondria

ASJC Scopus subject areas

  • Neuroscience(all)

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