Article
Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP
PLoS ONE
(2015)
Abstract
Mutations of the insulin/IGF signaling (IIS) pathway extend Drosophila lifespan. Based on
genetic epistasis analyses, this longevity assurance is attributed to downstream effects of
the FOXO transcription factor. However, as reported FOXO accounts for only a portion of
the observed longevity benefit, suggesting there are additional outputs of IIS to mediate
aging. One candidate is target of rapamycin complex 1 (TORC1). Reduced TORC1 activity
is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The
eukaryotic translation initiation factor 4E binding protein (4E-BP) is repressed by TORC1,
and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis
analyses to test whether longevity assurance mutants of chico, the Drosophila insulin
receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes,
which are robustly long-lived, d4eBP is required but not sufficient to slow aging.
Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity.
Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent
locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction
and most measures of growth affected by either chico genotype are always independent
of d4eBP. In females, chico heterozygotes paradoxically produce more rather than
less phosphorylated 4E-BP (p4E-BP). Altered IRS function within the IIS pathway of Drosophila
appears to have partial, conditional capacity to regulate aging through an unconventional
interaction with 4E-BP.
Disciplines
Publication Date
2015
DOI
10.1371/journal.pone.0134415
Publisher Statement
© 2015 Bai et al.
Citation Information
Hua Bai, Stephanie Post, Ping Kang and Marc Tatar. "Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP" PLoS ONE Vol. 10 Iss. 8 (2015) p. e0134415 Available at: http://works.bepress.com/hua-bai/5/
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