Figure 4.A framework for CR-dependent life span extension in D. melanogaster. CR treatment of flies leads to a funnel-effect: CR is a
highly pleiotropic process that influences a variety of biological processes,
including physiology, fertility, behavior and life span; the nature of most of
these pathways remains unknown. Under CR conditions (red), rpd3 is down- and
dSir2 is up regulated. dSir2 activity inhibits Dmp53 (amongst other targets),
leading to life span extension. The more up stream a gene is in this pathway,
the more likely it will mediate more of the pleiotropic aspects of CR, while
more down stream genes only mediate some aspects of the effects of CR. For
example, fertility is unchanged in dSir2- and DN-Dmp53 long-lived flies. Genetic
pathways affected by all three conditions (CR, dSir2, DN-Dmp53) could be
promising candidates for pathways directly influencing fly life span.
