Abstract
The detection of senescent cells has been challenging. We have recently developed a novel hybrid histo-/immunohisto-chemical method that can bypass several constraints of detection of senescent cells. It is based on the development of a novel reagent called GL13 (SenTraGorTM) that binds lipofuscin, a non-degradable metabolic by-product that is known as a hallmark of senescence. This chapter provides a unique approach to detect formalin fixed paraffin embedded tissues miRNAs in senescent GL13-reactive cells in routine. Given the significant role of miRNAs in senescent programs, this approach enables for the first time to monitor miRNAs in the context of senescence in situ in archival material. Notably, this assay improves our capacity to detect in vivo senescent cells which favors rationalization of senotherapeutic drugs. Although these agents are in early clinical trials, their introduction in routine practice will transform healthcare as we know it, bringing to the fore the necessity for precise detection of senescent cells in tissues.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abdelmohsen K, Gorospe M (2015) Noncoding RNA control of cellular senescence. Wiley Interdiscip Rev RNA 6(6):615–629
Allsopp RC, Chang E, Kashefi-Aazam M, Rogaev EI, Piatyszek MA, Shay JW et al (1995) Telomere shortening is associated with cell division in vitro and in vivo. Exp Cell Res 220:194–200
Bischof O, MartÃnez-Zamudio RI (2015) MicroRNAs and lncRNAs in senescence: a re-view. IUBMB Life 67(4):255–267
Campisi J (1997) The biology of replicative senescence. Eur J Cancer Part A 33(5):703–709
Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E (2019) From discoveries in ageing research to therapeutics for healthy ageing. Nature 571(7764):183–192
Childs BG, Baker DJ, Kirkland JL, Campisi J, Deursen JM (2014) Senescence and apoptosis: dueling or complementary cell fates? EMBO Rep 15(11):1139–1153
Cooks T, Theodorou SD, Paparouna E, Rizou SV, Myrianthopoulos V, Gorgoulis VG et al (2019) Immunohisto(cyto)chemistry: an old time classic tool driving modern oncological therapies. Histol Histopathol 34(4):335–352
Debacq-Chainiaux F, Ben Ameur R, Bauwens E, Dumortier E, Toutfaire M (2016) Toussaint O Stress-Induced (Premature) senescence, 243–262
Disayabutr S, Kim EK, Cha SI, Green G, Naikawadi RP, Jones KD et al (2016) MIR-34 MIRNAs regulate cellular senescence in type II alveolar epithelial cells of patients with idiopathic pulmonary fibrosis. PLoS ONE 11(6):1–15
Evangelou K, Gorgoulis VG (2017) Sudan black b, the specific histochemical stain for lipofuscin: a novel method to detect senescent cells. Methods Mol Biol 1534:111–119
Evangelou K, Lougiakis N, Rizou SV, Kotsinas A, Kletsas D, Muñoz-EspÃn D et al (2017) Robust, universal biomarker assay to detect senescent cells in biological specimens. Aging Cell 16(1):192–197
Gorgoulis VG, Halazonetis TD (2010) Oncogene-induced senescence: the bright and dark side of the response. Curr Opin Cell Biol 22(6):816–827
Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C et al (2019) Cellular senescence: defining a path forward. Cell 179(4):813–827
Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25(7):585–621
He L, He X, Lowe SW, Hannon GJ (2007) MicroRNAs join the p53 network–another piece in the tumour-suppression puzzle. Nat Rev Cancer 7(11):819–822
Kirkland JL, Tchkonia T, Zhu Y, Niedernhofer LJ, Robbins PD (2017) The clinical potential of senolytic drugs. J Am Geriatr Soc 65(10):2297–2301
Komseli ES, Pateras IS, Krejsgaard T, Stawiski K, Rizou SV, Polyzos A et al (2018) A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence. BMC Genom 19(1):1–22
Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB (1992) Telomere end-replication problem and cell aging. J Mol Biol 225(4):951–960
Munk R, Panda AC, Grammatikakis I, Gorospe M, Abdelmohsen K(2018) Senescence-associated microRNAs. In: International review of cell and molecular biology, vol 334, 1st edn. Elsevier Inc, pp 1–26
Muñoz-EspÃn D, Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15(7):482–496
Myrianthopoulos V, Evangelou K, Vasileiou PVS, Cooks T, Vassilakopoulos TP, Pangalis GA et al (2019) Senescence and senotherapeutics: a new field in cancer therapy. Pharmacol Ther 193:31–49
Vester B, Wengel J (2004) LNA (Locked Nucleic Acid): high-affinity targeting of complementary RNA and DNA. Biochemistry 43(42):13233–13241
Acknowledgements
Financial support was from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grants agreement No. 722729 (SYNTRAIN); the Welfare Foundation for Social & Cultural Sciences (KIKPE), Greece; Pentagon Biotechnology Ltd, UK and NKUA-SARG grants No 70/3/8916, 70/3/12128.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Ethics declarations
The authors wish to declare no conflict of interest.
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Pateras, I.S. et al. (2020). In Situ Detection of miRNAs in Senescent Cells in Archival Material. In: Muñoz-Espin, D., Demaria, M. (eds) Senolytics in Disease, Ageing and Longevity. Healthy Ageing and Longevity, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-030-44903-2_8
Download citation
DOI: https://doi.org/10.1007/978-3-030-44903-2_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-44902-5
Online ISBN: 978-3-030-44903-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)