Trace element effects on longevity and neurodegeneration with focus on C. elegans
Performing in vivo studies with Caenorhabditis elegans (C. elegans) as a model system offers several intrinsic advantages to study age-related changes such as behavioral and biochemical studies of macromolecules in the context of a whole organism. Characteristics that have contributed to its utility as a model include the easy maintenance, the well-developed genetics and the amenability to transgenesis. Additionally the highly conserved neurological pathways emerges the worm as powerful tool to study age-related neurodegenerative diseases. Current understandings in trace elements (TE) research in the nematode implicate that the maintenance of the TE homeostasis is of central importance for “healthy aging”. Alterations may contribute to aging phenotypes and are further supposed to be a risk factor for neurodegenerative disorders. Though it is known that single TE affect the homeostasis of the other, the interaction of the TE as well as a possible alteration of the TE homeostasis in the background of aging and age-related neurodegenerative disorders is not understood and needs to be clarified. Therefore, we determine the TE status during aging in wildtype animals as well as in transgenic neurodegenerative disease animals. These will be compared to the TE status of young and old human EPIC participants. To address the question whether changes in the TE status possess a vulnerability to aging worms and age-specific neurodegenerative disorders we conduct experiments incubating ‘young-adapted’ and ‘old-adapted’ TE diets at different ages mimicking the TE supply of young and old human EPIC participants. Additionally a `neuronal disease-adapted` diet will be exposed which is examined in the transgenic neurodegenerative disease animals. To assess the impact of the TE status on the neuronal aging the TE diets will also be fed in the neuronal disease models. Studies counter-regulating altered TE`s in the profiles might be ameliorative enabling “healthy aging”. Moreover the genetic factors influencing aging and age-specific neurodegenerative disorders will be taken into account since the three-way intersection of aging, genetics and TE levels represents a key gap in our understanding of the respective pathologies.