Goal
To understand the causes of human aging at a molecular genetic level and to use this information to slow the aging process.

Research Model
The nematode Caenorhabditis elegans. I focus specifically on the Mit mutants which (paradoxically) have disruptions in their mitochondrial electron transport chain yet are long-lived.  

Advantages of Model
Short lifespan (~20 days), self-fertilizing, powerful genetics, easily and cheaply cultivated, excellent molecular and bioinformatic resources.  

Relevance of Model to Humans
25% of worm genes have human orthologues. Pathways already known to influence aging in C. elegans act similarly in humans (e.g. insulin/IGF-1 like receptor). Mitochondria function similarly in almost all eucaryotes.  

Key Findings to Date
Life extension in the Mit mutants is restricted to a specific window of mitochondrial dysfunction. The Mit mutants provide a new model for several human mitochondrial-associated diseases. Nuclear DNA damage, cell-cycle checkpoint functions, alternate metabolic pathways and ROS signalling appear to be central players in lifespan regulation of the Mit mutants.   

Future Directions
Exploration of the connection between functionally impaired mitochondria, nuclear checkpoint proteins and life extension in the Mit mutants. Metabolic fingerprinting of the Mit mutants (already funded). Biochemical and biophysical characterization of the mitochondria from long-lived and short-lived mitochondrial mutants (already funded). Investigation of compensatory biochemical mechanisms that act to offset partial mitochondrial inhibition. Translation of our work into higher eucaryotes. Amelioration of human mitochondrial-associated diseases.