Abstract
The heterogeneity and multigenetic nature of nervous system aging make modeling of it a formidable task in mammalian species. The powerful genetics, simple anatomy and short life span of the nematode Caenorhabditis elegans offer unique advantages in unraveling the molecular genetic network that regulates the integrity of neuronal structures and functions during aging. In this review, we first summarize recent breakthroughs in the morphological and functional characterization of C. elegans neuronal aging. Age-associated morphological changes include age-dependent neurite branching, axon beading or swelling, axon defasciculation, progressive distortion of the neuronal soma, and early decline in presynaptic release function. We then discuss genetic pathways that modulate the speed of neuronal aging concordant with alteration in life span, such as insulin signaling, as well as cell-autonomous factors that promote neuronal integrity during senescence, including membrane activity and JNK/MAPK signaling. As a robust genetic model for aging, insights from C. elegans neuronal aging studies will contribute to our mechanistic understanding of human brain aging.
Highlights
Aging is the common path that all organisms take to reach the ultimate end of a life time’s journey
Modeling human brain aging per se, receives relatively little attention. This dichotomy partly arises from the fact that mutations in single genes are associated with some forms of familial Alzheimer disease (AD) or Parkinson’s disease (PD), whereas few such mutations, if any, had been discovered to alter neuronal aging
Even with several major differences in the architecture and molecular composition, C. elegans neurons display cardinal features of aging that are common to the nervous system in mammals
Summary
Aging is the common path that all organisms take to reach the ultimate end of a life time’s journey. A reduction in the density of synaptic vesicles was documented at the synapses in the nerve ring, the major neuropil of C. elegans [32] While these reports confirmed the conclusion made by earlier studies that there were no neuronal loss or axon placement defects in aging C. elegans, they clearly demonstrated that age-dependent deterioration of neuronal structures does occur at the subcellular level. Since daf-16 functions largely outside the nervous system to regulate C. elegans life span [1,2], this observation indicates that accelerated neuronal aging in the daf-16 mutant is a consequence of shortened life span at the whole animal level These findings are consistent with a recent report that homeostasis of protein quality control, an important factor in cellular aging, in the C. elegans muscles could be regulated non-autonomously [57].
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