RT Journal Article
SR Electronic
T1 Neurite Sprouting and Synapse Deterioration in the Aging <em>Caenorhabditis elegans</em> Nervous System
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8778
OP 8790
DO 10.1523/JNEUROSCI.1494-11.2012
VO 32
IS 26
A1 Toth, Marton Lorant
A1 Melentijevic, Ilija
A1 Shah, Leena
A1 Bhatia, Aatish
A1 Lu, Kevin
A1 Talwar, Amish
A1 Naji, Haaris
A1 Ibanez-Ventoso, Carolina
A1 Ghose, Piya
A1 Jevince, Angela
A1 Xue, Jian
A1 Herndon, Laura A.
A1 Bhanot, Gyan
A1 Rongo, Chris
A1 Hall, David H.
A1 Driscoll, Monica
YR 2012
UL http://www.jneurosci.org/content/32/26/8778.abstract
AB 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.