Apoptosis and Life-long Caloric RestrictionPI: Leeuwenburgh, Christiaan, PhD
Funding Agency: NIH
Agency Project Number: R01AG021042
Start Date: Aug 1, 2003
End Date: Jul 31, 2009
We hypothesize that experimentally-induced endogenous increases in mitochondrial oxidant production, or low exogenous addition of oxidants and/or calcium will result in the release of pro-apoptotic proteins, caspase activation, and subsequent activation of the mitochondrial-mediated pathway in young and old animals.
We hypothesize that doxorubicin will activate the mitochondrial-mediated pathway and increase the number of post mitotic cells that will undergo apoptosis. Moreover, we hypothesize that this will occur at greater levels in old compared to young animals. In addition we will determine the response of apoptotic inhibitors such as ARC (apoptosis repressor with a caspase recruitment domain [CARD] and X-linked inhibitor-of-apoptosis protein (XIAP).
We will determine apoptosis and alterations in the activation of the signal transduction pathways in 6-, 12-, 18-, 24-, and 26-month old normally aging Fischer 344 rats.
We hypothesize that caloric restriction _ an intervention which reduces oxidant production, improves calcium handling, and increases maximum lifespan in rodents _ will reduce the extent of apoptosis with age.
Christiaan Leeuwenburgh, Ph.D.
David Julian, Ph.D.
Gustavo Barja, Ph.D.
Steffi Wohlgemuth, Ph.D.