The Board of Trustees decided to honour Prof. Halloran with an honorary founder’s award in recognition of his dedication to the Foundation of the ROTRF and his excellence in scientific research. Prof. Halloran’s letter of intent and full paper submission were reviewed with the same evaluation process by the SAC as all other grants and were both highly rated by the SAC.
- Prof. Philip Halloran, Principal Investigator
- Dr. Calvin Harley,
- Dr. Walter Funk,
- Dr. Nam Kim,
- Dr. Kim Solez
- Dr. Ron Moore,
- Dr. Gerald Todd
- University of Alberta, Edmonton, Canada
- Exploring How Aging Mechanisms Affect Transplants
Background: Kidneys from older donors are more prone to fail but the mechanism for this is not known. This is concerning since the organ shortage forces us to use older donors. In addition some evidence suggests that aging may be accelerated in transplants because of the abnormal stresses of transplantation. Aging changes reflect the presence of "clocks" in the tissue, one of which may be the ends of the chromosomes, the "telomeres". Telomeres shorten with age until critically short telomeres cause cells to die. We recently showed that telomere shortening can be detected in old kidneys.
Hypothesis: 1. Old kidneys will show changes like "senescent" cells in culture. 2. Transplantation accelerates the aging process in kidneys.
Proposal: To examine telomere shortening and patterns of senescence gene expression in normal and diseased kidneys and in kidney transplants; to determine whether transplantation accelerates telomere shortening.
A. Reading the "clocks" in kidneys: We will establish new methods to measure telomeres. We will see if these changes are related to kidney function, how tissues change as the clocks advance, and whether kidney disease changes the clocks.
B. Senescence and stress changes in transplanted kidneys at the time of transplantation in relationship to the clinical course: We will determine whether telomere length in kidney at donation predicts transplant function and survival. We will determine whether telomere shortening and senescence is increased in kidneys developing chronic allograft nephropathy (CAN).
C. Mouse M Spretus has telomeres like humans and can be used to test whether injury advances the aging clocks.
Significance: Understanding aging and "senescence" may permit us to predict transplant survival and may guide treatment to avoid additional injury in kidneys at high risk of CAN. We may better decide which old organs can be used safely.