Strategies for Stage-Specific Extension of Longevity

It is generally recognized that the adult life span of Drosophila is not a continuous process from fertilization to death, but rather consists of four demographically defined phases: the developmental, health, transition, and senescent spans. These are marked by differences in gene expression patterns, physiology, homeostasis, and mortality rates. I review our empirical data showing that drugs known to significantly extend longevity in either early or late life do so via stage-specific effects such that beneficial effects are observed at one stage but neutral or detrimental effects at another stage. Whole-life feeding of these drugs leads to failure to detect their pro-longevity effect, suggesting that the gene-based drug targets are not necessarily present in all four stages.