The genetic and molecular analysis of aging in model systems has made exceptional strides. Certain themes have emerged that appear to have broad applicability. In addition, the participation of mitochondria in aging has taken on new dimensions, and the realization that organelle integrity and cross-talk play a role in cellular aging, likely including stem cell aging, is becoming evident. The long-term objective of the proposed research is to exploit the yeast model system for a better understanding of these emerging insights, with the goal of ameliorating aging decline in humans. The pathway that signals mitochondrial dysfunction to the nucleus, called the retrograde response, will be examined in detail in terms of its activation during normal aging. This will include an analysis of the requirements of the retrograde response genes for the maintenance of life span as cells age. The association of the main branches of the retrograde response with extended life span will be examined. The interaction between retrograde and Ras2 signaling will be dissected at the molecular level, and the signal proximal to mitochondria that triggers the retrograde response will be identified. The mechanisms underlying mitochondria-based age asymmetry between mother and daughter cells will be characterized by studying partition of newly-synthesized mitochondrial material and organelle turnover. The effects of these mechanisms on life span will be determined. The novel cross-talk between mitochondria and peroxisomes, which plays a role in age asymmetry will be examined at the molecular level, and the extent to which additional features of age asymmetry operate will be examined using a genetic approach.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AG006168-23
Application #
7795142
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Mccormick, Anna M
Project Start
1986-05-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
23
Fiscal Year
2010
Total Cost
$358,081
Indirect Cost
Name
Tulane University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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