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. 2012 Jan 1;125(1):7–17. doi: 10.1242/jcs.099200

Fig. 2.

Fig. 2.

Role of miRNAs in C. elegans aging. (A) lin-4 and lin-14 regulate lifespan in C. elegans. lin-4 loss-of-function mutants display shortened lifespans and various accelerated aging phenotypes, whereas lin-14 loss-of-function mutants exhibit extended longevity [not drawn to scale; see Boehm and Slack for lifespan curves (Boehm and Slack, 2005)]. lin-4 and LIN-14 are thought to function in the same pathway as DAF-2 and DAF-16, as illustrated in the lower part of this panel. Therefore, LIN-14 function during aging might result in direct repression of DAF-16 or indirect repression of DAF-16 through DAF-2 activation, which would in either case prevent DAF-16 from activating longevity genes. (B) miR-71, 238, 239, and 246 regulate lifespan in C. elegans. mir-71 mutants (as well as mir-238 and mir-246 mutants) have a shorter lifespan than wild-type animals, whereas mir-239 mutants have a longer lifespan [not drawn to scale; see de Lencastre et al for lifespan curves (de Lencastre et al., 2010)]. Shorter-lived C. elegans also display hallmarks of accelerated aging, such as increased stress sensitivity; the opposite holds true for longer-lived animals. The targets for some of these miRNAs have been established, as illustrated in the lower part of this panel: miR-71 targets AGE-1 and PDK-1 in the IIS pathway, as well as CDC-25.1 and CDK-1, which are involved in cell cycle checkpoints for DNA damage. Additionally, miR-239 activates AGE-1 and PDK-1 through unknown mechanisms (represented with question marks on the diagram).