The range of aging rates among animals is enormous. Both exceptionally slow and fast aging rates have evolved repeatedly. Within mammals, for instance, a comparatively species-poor group, there have been a m/n/mum of 9 instances of the independent evolution of exceptionally slow-aging. Are the cellular and molecular mechanisms underlying these separate evolutionary extensions of life similar, or are there many ways for nature to produce exceptionally slow aging? To what extent does cellular stress-resistance, commonly found associated with extended longevity in model organisms, comprise a general mechanism of aging? Are there gene expression """"""""signatures"""""""" that distinguish long- vs short-lived organisms, and could such signatures help identify fundamental aging processes? Are genetic alterations that lengthen life in the small array of""""""""model organisms,"""""""" such as worms and flies more broadly relevant across mammals, particularly with respect to long-lived species? Until recently, such questions were impossible to address in a comparative context. However advances in gene sequencing capability, phylogenetic information, and the implementation of high-throughput gene expression profiling techniques have now made these questions tractable. The proposed study will employ nine mammal species, carefully selected for their phylogenetic position and relative aging rates, to: (1) assess the extent to which cellular stress-resistance correlates with aging rate among mammals, and determine the utility of using cellular response to stress as a model and perhaps mechanism for modulation of senescence; (2) broadly compare induced gene expression differences associated with differing levels of cellular stress resistance across our spectrum of long- and short-lived species. A key feature of this specific aim is the development of a """"""""universal mammalian microarray,"""""""" specially designed for comparative mammalian aging studies; (3) broadly investigate the details of mitochondrial function across our range of long- and short-lived species to address the extent to which some common mitochondrial phenotype (e.g. low ROS production per level of electron flux) might generally affect aging rate.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG022873-03
Application #
6949989
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (O1))
Program Officer
Finkelstein, David B
Project Start
2003-09-30
Project End
2008-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$292,000
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Anatomy/Cell Biology
Type
Other Domestic Higher Education
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Ungvari, Zoltan; Csiszar, Anna; Sosnowska, Danuta et al. (2013) Testing predictions of the oxidative stress hypothesis of aging using a novel invertebrate model of longevity: the giant clam (Tridacna derasa). J Gerontol A Biol Sci Med Sci 68:359-67
Ungvari, Zoltan; Sosnowska, Danuta; Mason, Jeffrey B et al. (2013) Resistance to genotoxic stresses in Arctica islandica, the longest living noncolonial animal: is extreme longevity associated with a multistress resistance phenotype? J Gerontol A Biol Sci Med Sci 68:521-9
Csiszar, Anna; Podlutsky, Andrej; Podlutskaya, Natalia et al. (2012) Testing the oxidative stress hypothesis of aging in primate fibroblasts: is there a correlation between species longevity and cellular ROS production? J Gerontol A Biol Sci Med Sci 67:841-52
Ungvari, Zoltan; Ridgway, Iain; Philipp, Eva E R et al. (2011) Extreme longevity is associated with increased resistance to oxidative stress in Arctica islandica, the longest-living non-colonial animal. J Gerontol A Biol Sci Med Sci 66:741-50
Miller, Richard A; Williams, Joseph B; Kiklevich, J Veronika et al. (2011) Comparative cellular biogerontology: primer and prospectus. Ageing Res Rev 10:181-90
Austad, Steven N (2011) Candidate bird species for use in aging research. ILAR J 52:89-96
Fischer, Kathleen E; Austad, Steven N (2011) The development of small primate models for aging research. ILAR J 52:78-88
Bhattacharya, Arunabh; Leonard, Shanique; Tardif, Suzette et al. (2011) Attenuation of liver insoluble protein carbonyls: indicator of a longevity determinant? Aging Cell 10:720-3
Austad, Steven N (2010) Cats, ""rats,"" and bats: the comparative biology of aging in the 21st century. Integr Comp Biol 50:783-92
Austad, S N (2010) Methusaleh's Zoo: how nature provides us with clues for extending human health span. J Comp Pathol 142 Suppl 1:S10-21

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