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Differential patterns of apoptosis in response to aging in Drosophila

Zheng, Jie and Edelman, Scott W. and Tharmarajah, Grace and Walker, David W. and Pletcher, Scott D. and Seroude, Laurent (2005) Differential patterns of apoptosis in response to aging in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 102 (34). pp. 12083-12088. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:ZHEpnas05

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Abstract

Several lines of evidence suggest that programmed cell death may play a role in the aging process and the age-related functional declines of multicellular organisms. To pave the way for the use of Drosophila to rigorously test this hypothesis in a genetic model organism, this work examines the pattern of apoptosis in the adult fly during aging. The analysis across the lifespan of caspase activity and DNA fragmentation shows that apoptosis occurs in adult flies at all ages and that it is linked to physiological age. The results establish that under normal conditions, fly aging is coupled with a lifelong gradual increase of apoptosis within muscle cells and an activation of apoptosis in fat cells of old flies. The nervous system does not show signs of apoptosis. These time- and tissue-specific changes indicate that aging influences the levels and the nature of the cells that commit to apoptosis. The comparison with the apoptotic response to starvation and oxidative stresses strongly suggests that the lifelong increase in flight and leg muscles results from the accumulation of oxidative damage associated with aging. This finding presents an attractive mechanism to account for the decline of locomotor functions and muscle loss in the elderly and opens the way for the genetic analysis of sarcopenia in Drosophila.


Item Type:Article
Additional Information:Copyright © 2005 by the National Academy of Sciences. Edited by Jack E. Dixon, University of California at San Diego, La Jolla, CA, and approved July 8, 2005 (received for review April 23, 2005). Published online before print August 12, 2005, 10.1073/pnas.0503374102. We thank Rhonda Kristensen for technical assistance. This work was funded by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Institute of Aging of the Canadian Institutes of Health Research, and the Queen’s University Advisory Research Committee (to L.S.). J.Z. is supported by a NSERC graduate research fellowship. Author contributions: L.S. designed research; J.Z., S.W.E., G.T., D.W.W., and L.S. performed research; S.D.P. contributed new reagents/analytic tools; J.Z., S.W.E., G.T., and L.S. analyzed data; and J.Z., D.W.W., S.D.P., and L.S. wrote the paper. This paper was submitted directly (Track II) to the PNAS office.
Subject Keywords:GENE-EXPRESSION PROFILE; PROGRAMMED CELL-DEATH; OXIDATIVE STRESS; CALORIC RESTRICTION; SKELETAL-MUSCLE; MELANOGASTER; BRAIN; NEURONS; DEGENERATION; SENESCENCE
Record Number:CaltechAUTHORS:ZHEpnas05
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:ZHEpnas05
Alternative URL:http://dx.doi.org/10.1073/pnas.0503374102
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1618
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:22 Feb 2006
Last Modified:26 Dec 2012 08:45

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