@article{3253,
  keywords = {Animals, Caenorhabditis elegans, Signal Transduction, Aging, Caenorhabditis elegans Proteins, Oocytes, Insulin, Transcriptome, Cathepsin B},
  author = {Nicole Templeman and Shijing Luo and Rachel Kaletsky and Cheng Shi and Jasmine Ashraf and William Keyes and Coleen Murphy},
  title = {Insulin Signaling Regulates Oocyte Quality Maintenance with Age via Cathepsin B Activity.},
  abstract = { <p>A decline in female reproduction is one of the earliest hallmarks of aging in many animals, including invertebrates and mammals [1-4]. The insulin/insulin-like growth factor-1 signaling (IIS) pathway has a conserved role in regulating longevity [5] and also controls reproductive aging [2, 6]. Although IIS transcriptional targets that regulate somatic aging have been characterized [7, 8], it was not known whether the same mechanisms influence reproductive aging. We previously showed that Caenorhabditis elegans daf-2 IIS receptor mutants extend reproductive span by maintaining oocyte quality with age [6], but IIS targets in oocytes had not been identified. Here, we compared the transcriptomes of aged daf-2(-) and wild-type oocytes, and distinguished IIS targets in oocytes from soma-specific targets. Remarkably, IIS appears to regulate reproductive and somatic aging through largely distinct mechanisms, although the binding motif for longevity factor PQM-1 [8] was also overrepresented in oocyte targets. Reduction of oocyte-specific IIS targets decreased reproductive span extension and oocyte viability of daf-2(-) worms, and pqm-1 is required for daf-2(-){\textquoteright}s long reproductive span. Cathepsin-B-like gene expression and~activity levels were reduced in aged daf-2(-) oocytes, and RNAi against cathepsin-B-like W07B8.4 improved oocyte quality maintenance and extended reproductive span. Importantly, adult-only pharmacological inhibition of cathepsin B proteases reduced age-dependent deterioration in oocyte quality, even when treatment was initiated in mid-reproduction. This suggests that it is possible to pharmacologically slow age-related reproductive decline through mid-life intervention. Oocyte-specific IIS target genes thereby revealed potential therapeutic targets for maintaining reproductive health with age.</p> },
  year = {2018},
  journal = {Curr Biol},
  volume = {28},
  pages = {753-760.e4},
  month = {2018 Mar 05},
  issn = {1879-0445},
  doi = {10.1016/j.cub.2018.01.052},
  language = {eng},
}