This project focuses on identifying and characterizing genes that extend life span (LAG's) in Drosophila melanogaster. The main tool is a set of 120 recombinant inbred (R1) lines derived from artificially selected long-lived and control stocks.
Specific aims are (1) To test the hypothesis that LAG's pleiotropically affect other characters, including fertility and metabolic rate; (2) To execute fine-scale mapping and characterization of four QTL's identified on chromosomes 2 and 3, using single-nucleotide polymorphisms (SNPs); (3) To screen for point mutations and P-factor insertions that specifically after survival at the oldest ages; (4) To develop stocks for future research, including new RI's and lines that can reliably recover from freezing. Notable features of the proposed experiments are: (1) RI's derived from long-lived stocks are a unique and unusually valuable resource that took 4 years to construct; (2) The proposed research is a collaborative effort involving labs at 4 universities, (3) Experiments will be done on a large scale; the PI's lab routinely executes survival experiments with 100,000 flies; (4) It is important to study the RI's as soon as possible, because large sets of inbred lines tend to degenerate over time, due to the accumulation of new mutations and rare contamination; (5) Development of freeze-resistant flies is a high risk project that has the potential to revolutionize Drosophila research. Health relevance: It is important to test the pleiotropy hypotheses because they imply that interventions to extend life span my have deleterious effects early in life.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZAG1-PKN-2 (J1))
Program Officer
Mccormick, Anna M
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University of Minnesota Twin Cities
Schools of Arts and Sciences
United States
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Khazaeli, Aziz A; Van Voorhies, Wayne; Curtsinger, James W (2005) The relationship between life span and adult body size is highly strain-specific in Drosophila melanogaster. Exp Gerontol 40:377-85
Khazaeli, Aziz A; Van Voorhies, Wayne; Curtsinger, James W (2005) Longevity and metabolism in Drosophila melanogaster: genetic correlations between life span and age-specific metabolic rate in populations artificially selected for long life. Genetics 169:231-42
Nuzhdin, Sergey V; Khazaeli, Aziz A; Curtsinger, James W (2005) Survival analysis of life span quantitative trait loci in Drosophila melanogaster. Genetics 170:719-31
Luckinbill, L S; Reddy, S; Dudekonda, V et al. (2005) Analysis of two components of flight using recombinant inbred lines of Drosophila melanogaster. Genetica 124:235-45
Tahoe, Nuzha M A; Mokhtarzadeh, Ali; Curtsinger, James W (2004) Age-related RNA decline in adult Drosophila melanogaster. J Gerontol A Biol Sci Med Sci 59:B896-901
Van Voorhies, Wayne A; Khazaeli, Aziz A; Curtsinger, James W (2004) Testing the ""rate of living"" model: further evidence that longevity and metabolic rate are not inversely correlated in Drosophila melanogaster. J Appl Physiol 97:1915-22
Van Voorhies, Wayne A; Khazaeli, Aziz A; Curtsinger, James W (2004) Lack of correlation between body mass and metabolic rate in Drosophila melanogaster. J Insect Physiol 50:445-53
van Voorhies, Wayne A; Khazaeli, Aziz A; Curtsinger, James W (2003) Selected contribution: long-lived Drosophila melanogaster lines exhibit normal metabolic rates. J Appl Physiol 95:2605-13; discussion 2604
Minois, Nadege; Vaynberg, Sofia (2002) Fecundity and life span in transgenic Drosophila melanogaster overexpressing hsp70. Biogerontology 3:301-6
Tahoe, N M A; Dean, A M; Curtsinger, J W (2002) Nucleotide variations in the lxd region of Drosophila melanogaster: characterization of a candidate modifier of lifespan. Gene 297:221-8

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