Harinath, Girish, Guasp, Ryan, Toth, Marton, Xue, Jian, Patel, Khushboo, Gaul, Kelli, Zhang, Wenying, Driscoll, Monica, Ganihong, Ivana
[
International Worm Meeting,
2015]
Aging neurons in C. elegans and humans can experience dramatic morphological restructuring. In a recent screen for genes encoding proteins that maintain adult neuronal integrity we discovered a group of relatively poorly characterized EGF-like motif proteins. Systemic RNAi knockdown of these predicted calcium binding protein genes limited age-associated dendritic branching in touch neurons as much as 4 fold. Interestingly, for some genes, cell autonomous inactivation exacerbated morphological neuronal aging. Furthermore, we found some genes with cell non-autonomous actions on touch neuron maintenance. We found that systemic inactivation of certain EGF-like motif genes increase life- and healthspan, via a mechanism distinct from dietary restriction. These genes have conserved functions in cell adhesion and can thus serve as models with which to investigate crosstalk between the regulation of aging and tissue integrity, potentially assigning an entirely new function to this protein family.
Kim, Steven, Zhang, Wenying, DuBose, Camisha, Driscoll, Monica, Patel, Saurabh, Gaul, Kelli, Toth, Marton, Xue, Jian, Ganihong, Ivana, Patel, Khushboo
[
International Worm Meeting,
2013]
Human brain aging and cognitive decline are associated with synaptic changes and aberrant sprouting, rather than neuronal death. We have had a long-term interest in the genes and environmental factors that influence healthy tissue aging, using the facile experimental model C. elegans to decipher the basic biology of healthspan (the period of healthy maintenance prior to detectable functional or structural decline). Our initial study of how C. elegans tissues age indicated that, like in human brain aging, neither neuronal death nor axon degeneration is a significant feature of the aging nematode nervous system. However, specific C. elegans neuronal types can exhibit dramatic morphological changes (novel branching from processes, new outgrowth from cell bodies, wavy appearance) that increase in frequency with age. We have also shown that synaptic structures deteriorate in the aging C. elegans nervous system. Our findings support that C. elegans is a relevant model in which to study basic questions of nervous system aging, with anticipated findings likely informative on conserved mechanisms. The calcium-binding EF Hand motif can be found in a large number of protein families. This protein domain confers calcium regulation of proteins functions that include cytoplasmic calcium buffering, signal transduction, and muscle contraction. In a recent screen for genes that can influence the maintenance of adult neuronal integrity we discovered several previously uncharacterized EF Hand motif proteins with either neuroprotective or neurotoxic roles. RNAi knockdown of EF hand gene expression could accelerate or decrease neuronal aging up to 8 times, measured by our recently established branching and outgrowth markers of neuronal aging. We propose that EF Hand motif proteins and calcium play a substantial role in the maintenance of neuronal integrity in aging neurons.