PT  - JOURNAL ARTICLE
AU  - Marton Lorant Toth
AU  - Ilija Melentijevic
AU  - Leena Shah
AU  - Aatish Bhatia
AU  - Kevin Lu
AU  - Amish Talwar
AU  - Haaris Naji
AU  - Carolina Ibanez-Ventoso
AU  - Piya Ghose
AU  - Angela Jevince
AU  - Jian Xue
AU  - Laura A. Herndon
AU  - Gyan Bhanot
AU  - Chris Rongo
AU  - David H. Hall
AU  - Monica Driscoll
TI  - Neurite Sprouting and Synapse Deterioration in the Aging <em>Caenorhabditis elegans</em> Nervous System
AID  - 10.1523/JNEUROSCI.1494-11.2012
DP  - 2012 Jun 27
TA  - The Journal of Neuroscience
PG  - 8778--8790
VI  - 32
IP  - 26
4099  - http://www.jneurosci.org/content/32/26/8778.short
4100  - http://www.jneurosci.org/content/32/26/8778.full
SO  - J. Neurosci.2012 Jun 27; 32
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.