Further Extension of Lifespan by <i>Unc-43/CaMKII</i> and <i>Egl-8/PLCβ</i> Mutations in Germline-Deficient <i>Caenorhabditis elegans</i>

Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) promotes longevity across species. In the nematode <i>Caenorhabditis elegans</i>, ablation of germline stem cells (GSCs) and activity changes of the conserved signaling mediators <i>unc-43/CaMKII</i> (ca...

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Main Authors: Hildegard I. D. Mack, Laura G. Buck, Sonja Skalet, Jennifer Kremer, Hao Li, Elisabeth K. M. Mack
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/22/3527
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author Hildegard I. D. Mack
Laura G. Buck
Sonja Skalet
Jennifer Kremer
Hao Li
Elisabeth K. M. Mack
author_facet Hildegard I. D. Mack
Laura G. Buck
Sonja Skalet
Jennifer Kremer
Hao Li
Elisabeth K. M. Mack
author_sort Hildegard I. D. Mack
collection DOAJ
description Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) promotes longevity across species. In the nematode <i>Caenorhabditis elegans</i>, ablation of germline stem cells (GSCs) and activity changes of the conserved signaling mediators <i>unc-43/CaMKII</i> (calcium/calmodulin-dependent kinase type II) and <i>egl-8/PLCβ</i> (phospholipase Cβ) also increase lifespan. Like IIS, these pathways depend on the conserved transcription factor <i>daf-16/FOXO</i> for lifespan extension, but how they functionally interact is unknown. Here, we show that altered <i>unc-43/egl-8</i> activity further increases the lifespan of long-lived GSC-deficient worms, but not of worms that are long-lived due to a strong reduction-of-function mutation in the insulin/IGF1-like receptor <i>daf-2</i>. Additionally, we provide evidence for <i>unc-43</i> and, to a lesser extent, <i>egl-8</i> modulating the expression of certain collagen genes, which were reported to be dispensable for longevity of these particular <i>daf-2</i> mutant worms, but not for other forms of longevity. Together, these results provide new insights into the conditions and potential mechanisms by which CaMKII- and PLCβ-signals modulate <i>C. elegans</i> lifespan.
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spelling doaj.art-d912b26fa9b0409382be19a67f0eda6b2023-11-24T07:56:53ZengMDPI AGCells2073-44092022-11-011122352710.3390/cells11223527Further Extension of Lifespan by <i>Unc-43/CaMKII</i> and <i>Egl-8/PLCβ</i> Mutations in Germline-Deficient <i>Caenorhabditis elegans</i>Hildegard I. D. Mack0Laura G. Buck1Sonja Skalet2Jennifer Kremer3Hao Li4Elisabeth K. M. Mack5Institute for Biomedical Aging Research, Leopold-Franzens-Universität Innsbruck, 6020 Innsbruck, AustriaInstitute for Biomedical Aging Research, Leopold-Franzens-Universität Innsbruck, 6020 Innsbruck, AustriaInstitute for Biomedical Aging Research, Leopold-Franzens-Universität Innsbruck, 6020 Innsbruck, AustriaDepartment of Hematology, Oncology and Immunology, Philipps-University Marburg, 35043 Marburg, GermanyDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USADepartment of Hematology, Oncology and Immunology, Philipps-University Marburg, 35043 Marburg, GermanyReduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) promotes longevity across species. In the nematode <i>Caenorhabditis elegans</i>, ablation of germline stem cells (GSCs) and activity changes of the conserved signaling mediators <i>unc-43/CaMKII</i> (calcium/calmodulin-dependent kinase type II) and <i>egl-8/PLCβ</i> (phospholipase Cβ) also increase lifespan. Like IIS, these pathways depend on the conserved transcription factor <i>daf-16/FOXO</i> for lifespan extension, but how they functionally interact is unknown. Here, we show that altered <i>unc-43/egl-8</i> activity further increases the lifespan of long-lived GSC-deficient worms, but not of worms that are long-lived due to a strong reduction-of-function mutation in the insulin/IGF1-like receptor <i>daf-2</i>. Additionally, we provide evidence for <i>unc-43</i> and, to a lesser extent, <i>egl-8</i> modulating the expression of certain collagen genes, which were reported to be dispensable for longevity of these particular <i>daf-2</i> mutant worms, but not for other forms of longevity. Together, these results provide new insights into the conditions and potential mechanisms by which CaMKII- and PLCβ-signals modulate <i>C. elegans</i> lifespan.https://www.mdpi.com/2073-4409/11/22/3527agingstress resistanceinsulin signalinggermline stem cellsRNA-seqcollagen
spellingShingle Hildegard I. D. Mack
Laura G. Buck
Sonja Skalet
Jennifer Kremer
Hao Li
Elisabeth K. M. Mack
Further Extension of Lifespan by <i>Unc-43/CaMKII</i> and <i>Egl-8/PLCβ</i> Mutations in Germline-Deficient <i>Caenorhabditis elegans</i>
Cells
aging
stress resistance
insulin signaling
germline stem cells
RNA-seq
collagen
title Further Extension of Lifespan by <i>Unc-43/CaMKII</i> and <i>Egl-8/PLCβ</i> Mutations in Germline-Deficient <i>Caenorhabditis elegans</i>
title_full Further Extension of Lifespan by <i>Unc-43/CaMKII</i> and <i>Egl-8/PLCβ</i> Mutations in Germline-Deficient <i>Caenorhabditis elegans</i>
title_fullStr Further Extension of Lifespan by <i>Unc-43/CaMKII</i> and <i>Egl-8/PLCβ</i> Mutations in Germline-Deficient <i>Caenorhabditis elegans</i>
title_full_unstemmed Further Extension of Lifespan by <i>Unc-43/CaMKII</i> and <i>Egl-8/PLCβ</i> Mutations in Germline-Deficient <i>Caenorhabditis elegans</i>
title_short Further Extension of Lifespan by <i>Unc-43/CaMKII</i> and <i>Egl-8/PLCβ</i> Mutations in Germline-Deficient <i>Caenorhabditis elegans</i>
title_sort further extension of lifespan by i unc 43 camkii i and i egl 8 plcβ i mutations in germline deficient i caenorhabditis elegans i
topic aging
stress resistance
insulin signaling
germline stem cells
RNA-seq
collagen
url https://www.mdpi.com/2073-4409/11/22/3527
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