Downregulation of MTOR Signaling Increases Stem Cell Population Telomere Length During Starvation of Immortal Planarians

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2019 Jul 30

PMID 31353226

Citations 13

Authors

Marta Iglesias

Daniel A Felix

Oscar Gutierrez-Gutierrez

Maria Del Mar De Miguel-Bonet

Sounak Sahu

Beatriz Fernandez-Varas

Rosario Perona

A Aziz Aboobaker

Ignacio Flores

Cristina Gonzalez-Estevez

Affiliations

Soon will be listed here.

Abstract

Reduction of caloric intake delays and prevents age-associated diseases and extends the life span in many organisms. It may be that these benefits are due to positive effects of caloric restriction on stem cell function. We use the planarian model Schmidtea mediterranea, an immortal animal that adapts to long periods of starvation by shrinking in size, to investigate the effects of starvation on telomere length. We show that the longest telomeres are a general signature of planarian adult stem cells. We also observe that starvation leads to an enrichment of stem cells with the longest telomeres and that this enrichment is dependent on mTOR signaling. We propose that one important effect of starvation for the rejuvenation of the adult stem cell pool is through increasing the median telomere length in somatic stem cells. Such a mechanism has broad implications for how dietary effects on aging are mediated at the whole-organism level.

Citing Articles

Health Benefits of Intermittent Fasting.

Reddy B, Reddy V, Saier Jr M Microb Physiol. 2024; 34(1):142-152.

PMID: 38955141 PMC: 11262566. DOI: 10.1159/000540068.

Joint Effects of Exercise and Ramadan Fasting on Telomere Length: Implications for Cellular Aging.

Almuraikhy S, Sellami M, Naja K, Al-Amri H, Anwardeen N, Aden A Biomedicines. 2024; 12(6).

PMID: 38927389 PMC: 11200901. DOI: 10.3390/biomedicines12061182.

Telomere length and dynamics in cave and surface morphs.

Lunghi E, Bilandzija H PeerJ. 2024; 12:e16957.

PMID: 38435987 PMC: 10908260. DOI: 10.7717/peerj.16957.

Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells.

Wang Y, Jin S, Luo D, He D, Yu M, Zhu L Bone Res. 2023; 11(1):54.

PMID: 37872152 PMC: 10593834. DOI: 10.1038/s41413-023-00288-3.

The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting.

Shabkhizan R, Haiaty S, Moslehian M, Bazmani A, Sadeghsoltani F, Bagheri H Adv Nutr. 2023; 14(5):1211-1225.

PMID: 37527766 PMC: 10509423. DOI: 10.1016/j.advnut.2023.07.006.

References

Gonzalez-Garcia M, Pavelescu I, Canela A, Sevillano X, Leehy K, Nelson A . Single-cell telomere-length quantification couples telomere length to meristem activity and stem cell development in Arabidopsis. Cell Rep. 2015; 11(6):977-989. PMC: 4827700. DOI: 10.1016/j.celrep.2015.04.013. View

Tinkum K, Stemler K, White L, Loza A, Jeter-Jones S, Michalski B . Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival. Proc Natl Acad Sci U S A. 2015; 112(51):E7148-54. PMC: 4697381. DOI: 10.1073/pnas.1509249112. View

Kobayashi S, Yamada M, Asaoka M, Kitamura T . Essential role of the posterior morphogen nanos for germline development in Drosophila. Nature. 1996; 380(6576):708-11. DOI: 10.1038/380708a0. View

Behrens A, van Deursen J, Rudolph K, Schumacher B . Impact of genomic damage and ageing on stem cell function. Nat Cell Biol. 2014; 16(3):201-7. PMC: 4214082. DOI: 10.1038/ncb2928. View

Sato K, Shibata N, Orii H, Amikura R, Sakurai T, Agata K . Identification and origin of the germline stem cells as revealed by the expression of nanos-related gene in planarians. Dev Growth Differ. 2006; 48(9):615-28. DOI: 10.1111/j.1440-169X.2006.00897.x. View

Richmond C, Shah M, Deary L, Trotier D, Thomas H, Ambruzs D . Dormant Intestinal Stem Cells Are Regulated by PTEN and Nutritional Status. Cell Rep. 2015; 13(11):2403-2411. PMC: 4691543. DOI: 10.1016/j.celrep.2015.11.035. View

Kawauchi K, Ihjima K, Yamada O . IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells. J Immunol. 2005; 174(9):5261-9. DOI: 10.4049/jimmunol.174.9.5261. View

Saxton R, Sabatini D . mTOR Signaling in Growth, Metabolism, and Disease. Cell. 2017; 169(2):361-371. DOI: 10.1016/j.cell.2017.03.035. View

Bowling S, di Gregorio A, Sancho M, Pozzi S, Aarts M, Signore M . P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development. Nat Commun. 2018; 9(1):1763. PMC: 5932021. DOI: 10.1038/s41467-018-04167-y. View

10.

Koprunner M, Thisse C, Thisse B, Raz E . A zebrafish nanos-related gene is essential for the development of primordial germ cells. Genes Dev. 2001; 15(21):2877-85. PMC: 312811. DOI: 10.1101/gad.212401. View

11.

Huang J, Nguyen-McCarty M, Hexner E, Danet-Desnoyers G, Klein P . Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathways. Nat Med. 2012; 18(12):1778-85. PMC: 3518679. DOI: 10.1038/nm.2984. View

12.

Pucci F, Gardano L, Harrington L . Short telomeres in ESCs lead to unstable differentiation. Cell Stem Cell. 2013; 12(4):479-86. PMC: 3629568. DOI: 10.1016/j.stem.2013.01.018. View

13.

Eisenhoffer G, Kang H, Sanchez Alvarado A . Molecular analysis of stem cells and their descendants during cell turnover and regeneration in the planarian Schmidtea mediterranea. Cell Stem Cell. 2008; 3(3):327-39. PMC: 2614339. DOI: 10.1016/j.stem.2008.07.002. View

14.

Schneider R, Garrobo I, Foronda M, Palacios J, Marion R, Flores I . TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells. Nat Commun. 2013; 4:1946. DOI: 10.1038/ncomms2946. View

15.

Flores I, Blasco M . The role of telomeres and telomerase in stem cell aging. FEBS Lett. 2010; 584(17):3826-30. DOI: 10.1016/j.febslet.2010.07.042. View

16.

Molenaar C, Wiesmeijer K, Verwoerd N, Khazen S, Eils R, Tanke H . Visualizing telomere dynamics in living mammalian cells using PNA probes. EMBO J. 2003; 22(24):6631-41. PMC: 291828. DOI: 10.1093/emboj/cdg633. View

17.

Solana J . RNA In Situ Hybridization on Planarian Paraffin Sections. Methods Mol Biol. 2018; 1774:393-404. DOI: 10.1007/978-1-4939-7802-1_13. View

18.

Tu K, Pearson B, Sanchez Alvarado A . TORC1 is required to balance cell proliferation and cell death in planarians. Dev Biol. 2012; 365(2):458-69. PMC: 3367000. DOI: 10.1016/j.ydbio.2012.03.010. View

19.

Scimone M, Kravarik K, Lapan S, Reddien P . Neoblast specialization in regeneration of the planarian Schmidtea mediterranea. Stem Cell Reports. 2014; 3(2):339-52. PMC: 4176530. DOI: 10.1016/j.stemcr.2014.06.001. View

20.

Felix D, Gutierrez-Gutierrez O, Espada L, Thems A, Gonzalez-Estevez C . It is not all about regeneration: Planarians striking power to stand starvation. Semin Cell Dev Biol. 2018; 87:169-181. DOI: 10.1016/j.semcdb.2018.04.010. View