Age-Related Phasic Patterns of Mitochondrial Maintenance in Adult Caenorhabditis elegans Neurons
Open accessAbstract
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. SIGNIFICANCE STATEMENT Using Caenorhabditis elegans as a model, we address long-standing questions: How does aging affect neuronal mitochondrial morphology, density, trafficking, and oxidative stress resistance? Are these age-related changes amenable to genetic manipulations that slow down the aging process? Our study illustrates that mitochondrial trafficking declines progressively from the first day of adulthood, whereas mitochondrial size, density, and resistance to oxidative stress undergo three distinct stages: increase in early adulthood, maintenance at high levels during mid-adulthood, and decline during late adulthood. Thus, our study characterizes mitochondrial aging profile at the level of a single neuron in its native environment and establishes the critical foundation for the future genetic and pharmacological dissection of factors that influence long-term mitochondrial maintenance in neurons.
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In DAF-2 mutants, age-related changes in mitochondrial morphology and density are mitigated, and mitochondrial trafficking is maintained at normal levels in adulthood.
“In DAF-2 mutants, age-related changes in mitochondrial morphology and density are mitigated, and mitochondrial trafficking is maintained at under normal levels in adulthood21.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [21]
Mitochondrial morphology and dynamics change in C. elegans neurons during ageing.
“Mitochondrial morphology and dynamics, which undergo several changes in the neurons of C. elegans during ageing21, are also affected by IIS.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [21]
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- Authors
- Morsci, N. S., Hall, D. H., Driscoll, M., & Sheng, Z.-H.
- Affiliations
- National Institutes of Health (US)
- Albert Einstein College of Medicine (US)
- Rutgers, The State University of New Jersey (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2016-01-27
- Volume
- 36
- Issue
- 4
- Pages
- 1373-1385
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4728731
- OpenAlex
- W2265611117
- Cited by
- 92
- References
- 67
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 13 · 2020: 12 · 2019: 9 · 2018: 8 · 2017: 10 · 2016: 4
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (OD010440, P40OD010440, R24OD010943)
- Directorate for Biological Sciences
- National Centre for Biological Sciences
- National Institute on Aging (R01AG046358)
- National Institute of Neurological Disorders and Stroke (NS002946, Z01NS003029, Z01NS002946, NS003029)
- National Center for Research Resources (R24RR012596)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial aging, neuronal mitochondria, mitochondrial maintenance, mitochondrial trafficking, mitochondrial morphology, mitochondrial density, oxidative stress resistance, Caenorhabditis elegans, daf-2 mutant, aging, neurodegeneration, single-neuron analysis
- MeSH terms
- Acceleration, Age Factors, Aging, Analysis of Variance, Animals, Hydrogen Peroxide, Microscopy, Electron, Mitochondria, Neurons, Caenorhabditis elegans, Oxidative Stress, Mitochondrial Proteins, Caenorhabditis elegans Proteins, Animals, Genetically Modified, RNA Interference, Green Fluorescent Proteins
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