Dietary restriction in Drosophila is dependent on mitochondrial efficiency and constrained by pre-existing extended longevity.

We tested the effects of dietary restriction (DR) on the standard w(1118) strain as well as on our previously described Ra and La strains and their reciprocal isogenic 'cybrid' lines containing heterologous nuclear-mitochondrial combinations. The w(1118) and Ra strains, but neither the La strains nor their 'cybrid' derivatives, are DR-inducible. The Ra and La animals are more robust than the w(1118) animals, and the Ra strain shows an upward shift in its DR threshold. The non-inducibility of the La strain suggests that it expresses a constituitive version of the inducible DR phenotype of its predecessor Ra strain. The difference in mitochondrial efficiency observed between the Ra and La mitochondria (Ross, 2000) has real effects on longevity in the adults: the presence of the more efficient La mitochondria enhances the longevity of an otherwise Ra animal; while the maximum longevity inherent in the La nuclear information cannot be fully expressed in the presence of the Ra mitochondria. Despite the absence of any demographic mathematical parameters robustly and uniquely associated with extended longevity, there are some common trends in that longer lived cohorts have a longer period of low and often constant early life mortality rates (comprising the "health span"), leading to a delayed onset of senescence as noted by the late life increase in age-specific mortality rates (comprising the "senescence span"). There is a genetic basis to this phenotype, but the context-dependence of the demographic data suggests that there is not likely to be only one mechanism or pathway involved in the DR response. In addition, the presence of live yeast had systemic strain specific effects such that it increased longevity in the w(1118) animals but decreased it in the Ra and derived lines. Higher density (4-10x) foods yielded a decreased longevity in all strains at the highest level, showing that malnutrition occurs at both low and high caloric levels.