Drosophila melanogaster

Drosophila melanogaster—the common fruit fly—extended aging research from worms to complex organisms with differentiated tissues, organs, and behaviors. Flies have hearts, brains, muscles, and immune systems; they can learn, remember, and age with symptoms resembling human senescence. When caloric restriction and sirtuin overexpression extended fly lifespan, the mechanisms discovered in yeast clearly operated in organisms with biological complexity approaching our own.

Fly genetics offers unmatched manipulation capabilities. The GAL4-UAS system enables gene expression in any specified tissue. Balancer chromosomes allow maintenance of lethal mutations. The FLP-FRT system creates genetic mosaics where specific cells differ genetically from their neighbors. These tools enabled experiments impossible in other organisms: expressing sirtuins only in neurons, only in muscle, only in fat body, determining which tissues must respond for lifespan extension. The answers surprised: tissue-specific interventions sometimes affected whole-organism aging, revealing systemic communication.

Drosophila research discovered that rapamycin—which inhibits TOR signaling—extends lifespan, a finding now confirmed from yeast to mice. Flies also revealed interactions between different longevity pathways: caloric restriction and reduced IIS signaling use partially overlapping mechanisms, but combining interventions can produce additive effects. Understanding pathway crosstalk in flies guides clinical thinking about combining interventions. The fly serves as a system complex enough for mechanistic insight yet simple enough for systematic genetic manipulation.