The first step in a genetic analysis of aging is to identify and characterize the genetic mutants and their controls that will be used. Such mutants or strains are initially identified by their effect on the life span. Yet many genetic interventions are known to have some effect on the life span without necessarily affecting the aging process. It is therefore necessary to prove that one is actually dealing with an aging mutant before one draws strong inferences from the data. Casarett's rules provide an operational test for doing so, relying as they do on the comparison of aging bio-markers in the experimental and reference strains. We show that our previously described genetically based long-lived NDC-L strain and its normal-lived NDC-R control strain differ only in the chronological age of expression of two behavioral and three physiological functional age biomarkers. They do not differ in the sequence or the physiological age of expression of these biomarkers. These two strains comply with the Casarett rules and thereby comprise a valid tool with which to conduct a comparative genetic analysis of aging. The implications of the available data are discussed, including the possibility that aging in these strains of Drosophila melanogaster may be the result of a multiphasic developmental process.
In the development of business enterprise simulations, designers use as their knowledge base theories and business fundamentals drawn from accounting, finance, marketing, economic, production, and management courses. A problem exists, however, as each discipline has alternative procedures, theories, and unresolved issues. Because the simulation designer must choose specific procedures and theories, the personal bias of the designer enters the picture and cannot be avoided even if the designer attempts to avoid bias. The learning benefits of a specific simulation are thereby affected by what is and is not chosen as the knowledge base.
A controlled chromosome substitution experiment was performed on a strain (NDC-L) selected for long life to determine if the genes responsible for the extended-longevity phenotype could be localized to any particular chromosome(s). All 27 different possible combinations of the three major chromosomes of Drosophila melanogaster were constructed and longevities were determined on 3875 individual animals of both sexes and analysed. The results are statistically significant and demonstrate that mean longevity is specified primarily by recessive genes on the third chromosome (c3). The extended longevity phenotype (ELP) is only expressed in those lines which are homozygous for the NDC-L type c3. Loci on the first (ci) and second (c2) chromosomes interact, both positively (ci) and negatively (c2), respectively, such that ci represses c2 which in turn represses c3. The ELP is fully expressed in the mutual presence and mutual absence of ci and c2. The significance of these results is discussed in the context of broader categories of molecular genetic mechanisms suggested previously to be involved in the modulation of longevity in Drosophila.
Our previous work has shown that the major genes involved in the expression of the extendedlongevity phenotype are located on the third chromosome. Furthermore, their expression is negatively and positively influenced by chromosomes 2 and 1, respectively. In this report we show that the expression of the extended-longevity phenotype is dependent on the larval environment. A controlled chromosome substitution experiment was carried out using a strain selected for long life (L) and its parent (R) strain. Twenty different combinations of the three major chromosomes were conducted and their longevities were determined under both high (HD) and low (LD) larval density conditions. The extended-longevity phenotype was only expressed under RD conditions. The chromosome interactions were not apparent under LD conditions. Density-shift experiments delineate a critical period for expression of the extended-longevity phenotype, extending from 60 h after egg laying (AEL) to 96 h AEL, during which the developing animal must be exposed to HD conditions if the extended-longevity phenotype is to be expressed. The change from HD to LD conditions is accompanied by statistically significant increases in body weight. The possible role of a dietary restriction phenomenon is examined and the implications of these findings discussed. It is now apparent, however, that the extended-longevity phenotype in Drosophila is a developmental genetic process.
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