Pathology Presents: Extending Lifespan- Worms, Mitochondria and Metabolic Engineering
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Shane L. Rea, PhD
Barshop Institute for Longevity and Aging Studies
Due to the central importance of mitochondria, their functional status is closely monitored within cells. Retrograde responses are signals that originate from compromised mitochondria but act within the nucleus to orchestrate adaptive gene-expression changes to resolve or reduce mitochondrial stress. Higher eukaryotes have evolved different kinds of retrograde responses that are triggered by a variety of stressors. One innovative approach to countering age-related decline of mitochondrial function is to exploit retrograde responses to prophylactically protect, or even rejuvenate, the mitochondrial network. In this regard, retrograde responses represent an untapped means by which to potentially ameliorate multiple age-related diseases simultaneously. In the nematode C. elegans, severe reduction of mitochondrial electron transport chain (ETC) activity shortens life, as in humans, but mild reduction extends life and this is a consequence of survival strategies that are invoked under these circumstances. I will discuss a novel retrograde response that my group has uncovered in C. elegans that is activated in the face of reduced ETC activity and which requires a p38 MAPK. I will also discuss an in silico approach that my group has been using to determine the extent to which metabolism, per se, underlies the rate at which cells age.