2016 Scientific Report

JEREMY VAN RAAMSDONK, PH.D.
Dr. Van Raamsdonk completed a Ph.D. in medical genetics at
the University of British Columbia in 2005. He joined VARI as an
Assistant Professor in 2012.
STAFF
AUDREY ANDERSON, B.S.
DYLAN DUES, B.S.
MEGAN SENCHUK, PH.D.
STUDENTS
JASON COOPER, B.S.
EMILY MACHIELA, B.S.
RESEARCH INTERESTS
As the average human life span continues to increase, the likelihood of an individual
developing a neurodegenerative disease also increases. Thus, there is a need to
understand the aging process and its role in the development of age-onset disorders
such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Our
research is focused on gaining insight into the aging process and the pathogenesis
of such diseases. Beyond benefit to the individual, this work has potential benefits
for society by decreasing health care costs and helping to maintain productivity and
independence to a later age.
The free radical theory of aging (FRTA) proposes that aging results from the
accumulation of oxidative damage caused by reactive oxygen species (ROS) generated
during normal metabolism. However, recent work in the worm Caenorhabditis elegans
has indicated that the relationship between ROS and life span is more complex.
Superoxide dismutase (SOD) is an enzyme that decreases the levels of ROS, but the
deletion of SOD genes (individually or in combination) does not decrease life span. In
fact, quintuple-mutant worms lacking all five sod genes live as long as wild-type worms
despite a markedly increased sensitivity to oxidative stress. Thus, it appears that while
oxidative damage increases with age, it does not cause aging, and the result with the
quintuple mutants suggests a balance between the pro-survival signaling and the toxic
effects of superoxide.
Recent evidence suggests that increased levels of superoxide can act as a pro-survival
signal that leads to increased longevity. This is demonstrated by life-span increases
following the deletion of the mitochondrial gene sod-2 and the treatment of wild-type
worms with the superoxide generator paraquat. Thus, one of the main goals of
this work is to uncover the mechanism by which superoxide-mediated pro-survival
signaling leads to increased longevity. Using a combination of genetic mutants and
RNA interference, we explore how increases in superoxide trigger the signal, how the
signal is transmitted, and which of the changes the signal introduces lead to increased
life span.
60 Van Andel Research Institute | Scientific Report