Biomedical subjects

J Vettraino

Publications and source records attributed to J Vettraino.

4 recordsLinked to original sources

PubMed2001

Direct selection for paraquat resistance in Drosophila results in a different extended longevity phenotype.

When normal-lived Ra strain Drosophila were indirectly selected for longevity, they gave rise to long-lived La strain animals with lower oxidized protein and lipid levels that were temporally coincident with higher antioxidant activities. We wanted to determine whether it was possible to create long-lived animals by a direct selection for increased antioxidant activities. Using the same Ra strain, we selected them over 24 generations for increased resistance to paraquat. Selection was successful: the paraquat-resistant flies had a fourfold increase in their LT(50) (mean lethal time) values. Their extended longevity pattern differs from that of the La strain. The paraquat-resistant animals also have a lower level of antioxidant activity, an increased total P450 enzyme activity level, an altered pattern of energy metabolism, and a significantly lower developmental viability. We interpret these findings as suggesting that similar stress response phenotypes may be generated by different molecular mechanisms, some of which may generate very different types of extended longevity phenotypes.

Animals↗

PubMed2000

Identical longevity phenotypes are characterized by different patterns of gene expression and oxidative damage.

Some years ago we applied simultaneously an identical regime of selection for late-life reproduction to several normal-lived sister lines (Ra and Rb) so as to produce several selected long-lived sister lines (La and Lb). The long-lived La and Lb sister lines had statistically identical longevity phenotypes and paraquat resistance phenotypes; however, we noticed some statistically different responses of the two strains at the biochemical level. Extensive work with the La strain showed that transcriptional alterations in antioxidant gene expression are robustly associated with its extended longevity. We decided to critically test the assumption of phenotypic equivalence by subjecting the Lb strain to the same series of molecular assays as was the La strain. The two sister strains are characterized by significantly different mechanisms and patterns of antioxidant gene expression, antioxidant enzyme activity, and oxidative damage. We find that the Lb strain appears to depend on the transcriptional activation of different genes than does the La strain, and on a post-translational up-regulation of at least one other antioxidant defense gene. The phenotypic equivalence observed at the organism level need not hold at the molecular genetic level. This finding suggests that there is more than one molecular mechanism by which antioxidant defense genes can bring about an increased resistance to oxidative stress. The theoretical and empirical implications of these findings are discussed.

Animals↗

PubMed2000

Forward and reverse selection for longevity in Drosophila is characterized by alteration of antioxidant gene expression and oxidative damage patterns.

Patterns of antioxidant gene expression and of oxidative damage were measured throughout the adult life span of a selected long-lived strain (La) of Drosophila melanogaster and compared to that of their normal-lived progenitor strain (Ra). Extended longevity in the La strain is correlated with enhanced antioxidant defense system gene expression, accumulation of CuZnSOD protein, and an increase in ADS enzyme activities. Extended longevity is strongly associated with a significantly increased resistance to oxidative stress. Reverse-selecting this long-lived strain for shortened longevity (RevLa strain) yields a significant decrease in longevity accompanied by reversion to normal levels of its antioxidant defense system gene expression patterns and antioxidant enzyme patterns. The significant effects of forward and reverse selection in these strains seem limited to the ADS enzymes; 11 other enzymes with primarily metabolic functions show no obvious effect of selection on their activity levels whereas six other enzymes postulated to play a role in flux control may actually be involved in NADPH reoxidation and thus support the enhanced activities of the ADS enzymes. Thus, alterations in the longevity of these Drosophila strains are directly correlated with corresponding alterations in; 1) the mRNA levels of certain antioxidant defense system genes; 2) the protein level of at least one antioxidant defense system gene; 3) the activity levels of the corresponding antioxidant defense system enzymes, and 4) the ability of the organism to resist the biological damage arising from oxidative stress.

Acatalasia↗

PubMed2000

Extended longevity in Drosophila is consistently associated with a decrease in developmental viability.

It has proven relatively easy to select normal-lived strains of Drosophila for extended longevity in the laboratory. Long-lived strains have not been observed in the wild as yet. Of the various life-history traits that have been investigated for their role in modulating the evolution of extended longevity, none have yet shown a consistent or convincing relationship. Other than developmental time, the traits usually investigated in this regard are those associated with the adult phase of the life cycle. We assayed developmental timing and viability in six pairs of normal- and long-lived strains, four pairs of which are from previously described strains and two pairs of which are new strains that have been independently and recently selected. We find that the life-history trait most obviously associated with all our long-lived strains is a significantly reduced developmental viability, with the long-lived strains' having as much as twice the developmental lethality as do any of the normal-lived strains. The long-lived strains also pupate closer to the food, a behavior known to decrease fitness. Thus the reduced fitness of the long-lived strains appears to be due to both physiological and behavioral factors and may well explain why long lived strains are not usually found in the wild. The extension of longevity involves costs as well as benefits that, in this case, are borne by different individuals.

Animals↗