Insulin Signaling Regulates Oocyte Quality Maintenance with Age via Cathepsin B Activity

Current Biology : CB
Nicole M TemplemanColeen T Murphy

Abstract

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(-)'s long reproductive span. Cathepsin-B-like gene expression and activity levels...Continue Reading

Citations

Oct 31, 2018·Journal of Assisted Reproduction and Genetics·Paulo Navarro-Costa
Oct 3, 2018·The Journal of Reproduction and Development·Xuerui YaoNam-Hyung Kim
Nov 2, 2019·Molecular Biology of the Cell·Coleen T Murphy
May 23, 2020·Current Biology : CB·Spencer S WongDennis H Kim
Jun 17, 2020·Developmental Cell·Nicole M TemplemanColeen T Murphy
Jul 27, 2021·Frontiers in Cell and Developmental Biology·Theadora Tolkin, E Jane Albert Hubbard
Jan 16, 2022·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Faria Athar, Nicole M Templeman

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