title: Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system.
abstract: Caenorhabditis elegans is a powerful model for analysis of the conserved mechanisms that modulate healthy aging. In the aging nematode nervous system, neuronal death and/or detectable loss of processes are not readily apparent, but because dendrite restructuring and loss of synaptic integrity are hypothesized to contribute to human brain decline and dysfunction, we combined fluorescence microscopy and electron microscopy (EM) to screen at high resolution for nervous system changes. We report two major components of morphological change in the aging C. elegans nervous system: (1) accumulation of novel outgrowths from specific neurons, and (2) physical decline in synaptic integrity. Novel outgrowth phenotypes, including branching from the main dendrite or new growth from somata, appear at a high frequency in some aging neurons, but not all. Mitochondria are often associated with age-associated branch sites. Lowered insulin signaling confers some maintenance of ALM and PLM neuron structural integrity into old age, and both DAF-16/FOXO and heat shock factor transcription factor HSF-1 exert neuroprotective functions. hsf-1 can act cell autonomously in this capacity. EM evaluation in synapse-rich regions reveals a striking decline in synaptic vesicle numbers and a diminution of presynaptic density size. Interestingly, old animals that maintain locomotory prowess exhibit less synaptic decline than same-age decrepit animals, suggesting that synaptic integrity correlates with locomotory healthspan. Our data reveal similarities between the aging C. elegans nervous system and mammalian brain, suggesting conserved neuronal responses to age. Dissection of neuronal aging mechanisms in C. elegans may thus influence the development of brain healthspan-extending therapies.
authors: Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors: Marton Lorant
authors: ML
authors: Toth
authors: Ilija
authors: I
authors: Melentijevic
authors: Leena
authors: L
authors: Shah
authors: Aatish
authors: A
authors: Bhatia
authors: Kevin
authors: K
authors: Lu
authors: Amish
authors: A
authors: Talwar
authors: Haaris
authors: H
authors: Naji
authors: Carolina
authors: C
authors: Ibanez-Ventoso
authors: Piya
authors: P
authors: Ghose
authors: Angela
authors: A
authors: Jevince
authors: Jian
authors: J
authors: Xue
authors: Laura A
authors: LA
authors: Herndon
authors: Gyan
authors: G
authors: Bhanot
authors: Chris
authors: C
authors: Rongo
authors: David H
authors: DH
authors: Hall
authors: Monica
authors: M
authors: Driscoll
mesh_terms: D000367:Age Factors; D000375:Aging / Q000473:pathology*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000166:cytology*; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000145:classification / Q000166:cytology* / Q000648:ultrastructure; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure; D014110:Touch / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans; D049452:Green Fluorescent Proteins; D011972:Receptor, Insulin