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.
|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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