Skip to main content

Potential Applications of Aptamers for Targeting Senescent Cells

  • Chapter
  • First Online:
Senolytics in Disease, Ageing and Longevity

Part of the book series: Healthy Ageing and Longevity ((HAL,volume 11))

Abstract

Cellular senescence is a stress response characterized by a permanent loss of proliferative ability. Different types of senescence reflect different forms of stress. Although cellular senescence plays a key role in maintaining tissue homeostasis and in suppressing tumorigenesis, it is widely appreciated that accumulation of senescent cells in tissue contributes to development of age-related dysfunctions and limits the efficacy of chemo- and radiotherapy. Consequently, novel therapeutic strategies targeting senescent cells, or their pro-inflammatory secretome, have been recently developed. The application of these novel therapeutic approaches requires biomarkers for in vivo detection of senescent cells for ageing and age-associated diseases, as well as for therapy-induced senescence in cancer patients. Aptamers are short oligonucleotide or peptide sequences able to bind with high affinity and specificity a wide range of cellular targets, including cell surface epitopes, thanks to their unique three-dimensional folding. Oligonucleotide aptamers have been widely applied for the discovery of biomarkers, since the early 1990s, and Affimers have recently emerged as valuable tools for biomarker discovery. In this chapter we briefly introduce applications of aptamer technologies for recognition of cell surface antigens and suggest that aptamers provide the perfect technology to identify novel senescence-specific biomarkers.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Acosta JC, O’Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S et al (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133(6):1006–1018

    Article  CAS  PubMed  Google Scholar 

  • Alimonti A, Nardella C, Chen Z, Clohessy JG, Carracedo A, Trotman LC et al (2010) A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J Clin Invest. 120(3):681–693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alspach E, Flanagan KC, Luo X, Ruhland MK, Huang H, Pazolli E et al (2014) p38MAPK plays a crucial role in stromal-mediated tumorigenesis. Cancer Discov 4(6):716–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Althubiti M, Lezina L, Carrera S, Jukes-Jones R, Giblett SM, Antonov A et al (2014) Characterization of novel markers of senescence and their prognostic potential in cancer. Cell Death Dis 5:e1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B et al (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J et al (2016) Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530(7589):184–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baraibar MA, Ladouce R, Friguet B (2013) Proteomic quantification and identification of carbonylated proteins upon oxidative stress and during cellular aging. J Proteomics 92:63–70

    Article  CAS  PubMed  Google Scholar 

  • Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N et al (2006) Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444(7119):633–637

    Article  CAS  PubMed  Google Scholar 

  • Berezovski MV, Lechmann M, Musheev MU, Mak TW, Krylov SN (2008) Aptamer-facilitated biomarker discovery (AptaBiD). J Am Chem Soc 130(28):9137–9143

    Article  CAS  PubMed  Google Scholar 

  • Biran A, Perelmutter M, Gal H, Burton DG, Ovadya Y, Vadai E et al (2015) Senescent cells communicate via intercellular protein transfer. Genes Dev 29(8):791–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borghesan M, Fafián-Labora J, Eleftheriadou O, Carpintero-Fernández P, Paez-Ribes M, Vizcay-Barrena G et al (2019) Small extracellular vesicles are key regulators of non-cell autonomous intercellular communication in senescence via the interferon protein IFITM3. Cell Rep. 27(13):3956–3971.e6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burgess DJ (2011) Senescence. NF-κB shows its beneficial side. Nat Rev Cancer 11(12):832–833

    Google Scholar 

  • Bussian TJ, Aziz A, Meyer CF, Swenson BL, van Deursen JM, Baker DJ (2018) Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 562(7728):578–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camorani S, Cerchia L, Fedele M, Erba E, D’Incalci M, Crescenzi E (2018) Trabectedin modulates the senescence-associated secretory phenotype and promotes cell death in senescent tumor cells by targeting NF-κB. Oncotarget. 9(28):19929–19944

    Article  PubMed  PubMed Central  Google Scholar 

  • Capell BC, Drake AM, Zhu J, Shah PP, Dou Z, Dorsey J et al (2016) MLL1 is essential for the senescence-associated secretory phenotype. Genes Dev 30(3):321–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen L, Rashid F, Shah A, Awan HM, Wu M, Liu A et al (2015) The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation. Proc Natl Acad Sci USA 112(32):10002–10007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chien Y, Scuoppo C, Wang X, Fang X, Balgley B, Bolden JE et al (2011) Control of the senescence-associated secretory phenotype by NF-κB promotes senescence and enhances chemosensitivity. Genes Dev 25(20):2125–2136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chondrogianni N, Petropoulos I, Grimm S, Georgila K, Catalgol B, Friguet B et al (2014) Protein damage, repair and proteolysis. Mol Aspect Med 35:1–71

    Article  CAS  Google Scholar 

  • Chong M, Yin T, Chen R, Xiang H, Yuan L, Ding Y et al (2018) CD36 initiates the secretory phenotype during the establishment of cellular senescence. EMBO Rep 19(6)

    Google Scholar 

  • Colas P, Cohen B, Jessen T, Grishina I, McCoy J, Brent R (1996) Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature 380(6574):548–550

    Article  CAS  PubMed  Google Scholar 

  • Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J et al (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6(12):2853–2868

    Article  PubMed  CAS  Google Scholar 

  • Correia-Melo C, Marques FD, Anderson R, Hewitt G, Hewitt R, Cole J et al (2016) Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO J 35(7):724–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cotarelo CL, Schad A, Kirkpatrick CJ, Sleeman JP, Springer E, Schmidt M et al (2016) Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes. Oncotarget 7(46):74846–74859

    Article  PubMed  PubMed Central  Google Scholar 

  • Crescenzi E, Pacifico F, Lavorgna A, De Palma R, D’Aiuto E, Palumbo G et al (2011) NF-κB-dependent cytokine secretion controls Fas expression on chemotherapy-induced premature senescent tumor cells. Oncogene 30(24):2707–2717

    Article  CAS  PubMed  Google Scholar 

  • d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T et al (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426(6963):194–198

    Google Scholar 

  • Demaria M, O’Leary MN, Chang J, Shao L, Liu S, Alimirah F et al (2017) Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov 7(2):165–176

    Article  CAS  PubMed  Google Scholar 

  • Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C et al (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444(7119):638–642

    Article  PubMed  CAS  Google Scholar 

  • Díaz-Fernández A, Miranda-Castro R, de-Los-Santos-Álvarez N, Lobo-Castañón MJ (2018) Post-translational modifications in tumor biomarkers: the next challenge for aptamers? Anal Bioanal Chem 410(8):2059–2065

    Google Scholar 

  • Dos Remedios C, Peckham M (2017) 3Rs and biophysics. Biophys Rev 9(4):277–278

    Article  PubMed  PubMed Central  Google Scholar 

  • Eggert T, Wolter K, Ji J, Ma C, Yevsa T, Klotz S et al (2016) Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression. Cancer Cell 30(4):533–547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346(6287):818–822

    Article  CAS  PubMed  Google Scholar 

  • Ellington AD, Szostak JW (1992) Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures. Nature 355(6363):850–852

    Article  CAS  PubMed  Google Scholar 

  • Evangelou K, Lougiakis N, Rizou SV, Kotsinas A, Kletsas D, Muñoz-Espín D et al (2017) Robust, universal biomarker assay to detect senescent cells in biological specimens. Aging Cell 16(1):192–197

    Article  CAS  PubMed  Google Scholar 

  • Farr JN, Xu M, Weivoda MM, Monroe DG, Fraser DG, Onken JL et al (2017) Targeting cellular senescence prevents age-related bone loss in mice. Nat Med 23(9):1072–1079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fitter S, James R (2005) Deconvolution of a complex target using DNA aptamers. J Biol Chem 280(40):34193–34201

    Article  CAS  PubMed  Google Scholar 

  • Frescas D, Roux CM, Aygun-Sunar S, Gleiberman AS, Krasnov P, Kurnasov OV et al (2017) Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody. Proc Natl Acad Sci USA 114(9):E1668–E1677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Freund A, Laberge RM, Demaria M, Campisi J (2012) Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell 23(11):2066–2075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friguet B (2002) Aging of proteins and the proteasome. Prog Mol Subcell Biol 29:17–33

    Article  CAS  PubMed  Google Scholar 

  • Fumagalli M, Rossiello F, Clerici M, Barozzi S, Cittaro D, Kaplunov JM et al (2012) Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol 14(4):355–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Georgakopoulou EA, Tsimaratou K, Evangelou K, Fernandez Marcos PJ, Zoumpourlis V, Trougakos IP et al (2013) Specific lipofuscin staining as a novel biomarker to detect replicative and stress-induced senescence. A method applicable in cryo-preserved and archival tissues. Aging (Albany NY) 5(1):37–50

    Google Scholar 

  • Georgilis A, Klotz S, Hanley CJ, Herranz N, Weirich B, Morancho B et al (2018) PTBP1-mediated alternative splicing regulates the inflammatory secretome and the pro-tumorigenic effects of senescent cells. Cancer Cell 34(1):85–102.e9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Germer K, Leonard M, Zhang X (2013) RNA aptamers and their therapeutic and diagnostic applications. Int J Biochem Mol Biol 4(1):27–40

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gilbert BA, Sha M, Wathen ST, Rando RR (1997) RNA aptamers that specifically bind to a K Ras-derived farnesylated peptide. Bioorg Med Chem 5(6):1115–1122

    Article  CAS  PubMed  Google Scholar 

  • Glück S, Ablasser A (2019) Innate immunosensing of DNA in cellular senescence. Curr Opin Immunol 56:31–36

    Article  PubMed  CAS  Google Scholar 

  • Gorisse L, Pietrement C, Vuiblet V, Schmelzer CE, Köhler M, Duca L et al (2016) Protein carbamylation is a hallmark of aging. Proc Natl Acad Sci USA 113(5):1191–1196

    Article  CAS  PubMed  Google Scholar 

  • Grabowska W, Kucharewicz K, Wnuk M, Lewinsk A, Suszek M, Przybylska D et al (2015) Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner. Age (Dordr) 37(1):9744

    Article  CAS  Google Scholar 

  • Hari P, Millar FR, Tarrats N, Birch J, Quintanilla A, Rink CJ et al (2019) The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype. Sci Adv 5(6):eaaw0254

    Google Scholar 

  • He F, Wen N, Xiao D, Yan J, Xiong H, Cai S et al (2018) Aptamer based targeted drug delivery systems: current potential and challenges. Curr Med Chem [Epub ahead of print]

    Google Scholar 

  • Hernandez-Segura A, de Jong TV, Melov S, Guryev V, Campisi J, Demaria M (2017) Unmasking Transcriptional Heterogeneity in Senescent Cells. Curr Biol 27(17):2652–2660.e4

    Google Scholar 

  • Hewitt G, Jurk D, Marques FD, Correia-Melo C, Hardy T, Gackowska A et al (2012) Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat Commun 3:708

    Article  PubMed  CAS  Google Scholar 

  • Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK et al (2019) Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine 47:446–456

    Article  PubMed  PubMed Central  Google Scholar 

  • Hills SA, Diffley JF (2014) DNA replication and oncogene-induced replicative stress. Curr Biol 24(10):R435–R444

    Article  CAS  PubMed  Google Scholar 

  • Hoare M, Ito Y, Kang TW, Weekes MP, Matheson NJ, Patten DA et al (2016) NOTCH1 mediates a switch between two distinct secretomes during senescence. Nat Cell Biol 18(9):979–992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes DJ, Tiede C, Penswick N, Tang AA, Trinh CH, Mandal U et al (2017) Generation of specific inhibitors of SUMO-1- and SUMO-2/3-mediated protein-protein interactions using Affimer (Adhiron) technology. Sci Signal 10(505):pii:eaaj2005

    Google Scholar 

  • Iannello A, Thompson TW, Ardolino M, Lowe SW, Raulet DH (2013) p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J Exp Med 210(10):2057–2069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itakura Y, Sasaki N, Kami D, Gojo S, Umezawa A, Toyoda M (2016) N- and O-glycan cell surface protein modifications associated with cellular senescence and human aging. Cell Biosci 6:14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jackson JG, Pant V, Li Q, Chang LL, Quintás-Cardama A, Garza D et al (2012) p53-mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. Cancer Cell 21(6):793–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeon OH, Kim C, Laberge RM, Demaria M, Rathod S, Vasserot AP et al (2017) Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat Med 23(6):775–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeon OH, Wilson DR, Clement CC, Rathod S, Cherry C, Powell B et al (2019) Senescence cell-associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers. JCI Insight 4(7):pii:125019

    Google Scholar 

  • Justice JN, Nambiar AM, Tchkonia T, LeBrasseur NK, Pascual R, Hashmi SK et al (2019) Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine 40:554–563

    Article  PubMed  PubMed Central  Google Scholar 

  • Karimi-Busheri F, Rasouli-Nia A, Mackey JR, Weinfeld M (2010) Senescence evasion by MCF-7 human breast tumor-initiating cells. Breast Cancer Res 12(3):R31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaur H, Bruno JG, Kumar A, Sharma TK (2018) Aptamers in the therapeutics and diagnostics pipelines. Theranostics 8(15):4016–4032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keefe AD, Pai S, Ellington A (2010) Aptamers as therapeutics. Nat Rev Drug Discov 9(7):537–550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SB, Bozeman RG, Kaisani A, Kim W, Zhang L, Richardson JA et al (2016) Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses. Oncogene 35(26):3365–3375

    Article  CAS  PubMed  Google Scholar 

  • Kim KM, Noh JH, Bodogai M, Martindale JL, Yang X, Indig FE et al (2017) Identification of senescent cell surface targetable protein DPP4. Genes Dev 31(15):1529–1534

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kirkland JL, Tchkonia T (2017) Cellular senescence: a translational perspective. EBioMedicine 21:21–28

    Article  PubMed  PubMed Central  Google Scholar 

  • Kovacovicova K, Skolnaja M, Heinmaa M, Mistrik M, Pata P, Pata I et al (2018) Senolytic cocktail Dasatinib+Quercetin (D+Q) does not enhance the efficacy of senescence-inducing chemotherapy in liver cancer. Front Oncol 8:459

    Article  PubMed  PubMed Central  Google Scholar 

  • Kratschmer C, Levy M (2017) Effect of chemical modifications on aptamer stability in serum. Nucleic Acid Ther 27(6):335–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuilman T, Peeper DS (2009) Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer 9(2):81–94

    Article  CAS  PubMed  Google Scholar 

  • Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ et al (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133(6):1019–1031

    Article  CAS  PubMed  Google Scholar 

  • Kurz DJ, Decary S, Hong Y, Erusalimsky JD (2000) Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci 113(Pt 20):3613–3622

    CAS  PubMed  Google Scholar 

  • Kyle S (2018) Affimer proteins: theranostics of the future? Trends Biochem Sci 43(4):230–232

    Article  CAS  PubMed  Google Scholar 

  • Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L et al (2015) MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol 17(8):1049–1061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lai WY, Huang BT, Wang JW, Lin PY, Yang PC (2016) A novel PD-L1-targeting antagonistic DNA aptamer with antitumor effects. Mol Ther Nucleic Acids 5(12):e3977

    Google Scholar 

  • Larsen AK, Galmarini CM, D’Incalci M (2016) Unique features of trabectedin mechanism of action. Cancer Chemother Pharmacol 77(4):663–671

    Article  CAS  PubMed  Google Scholar 

  • Li L (2007) Detection of protein biomarkers using RNA aptamer microarrays and enzymatically amplified surface plasmon resonance imaging. Anal Chem 79(3):1082–1088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin CH, Patel DJ (1997) Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP. Chem Biol 4(11):817–832

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Uppal H, Demaria M, Desprez PY, Campisi J, Kapahi P (2015) Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. Sci Rep 5:17895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S, Mahairaki V, Bai H, Ding Z, Li J, Witwer KW et al (2019) Highly purified human extracellular vesicles produced by stem cells alleviate aging cellular phenotypes of senescent human cells. Stem Cells 37(6):779–790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Llanos S, Serrano M (2016) Senescence and cancer: in the name of immunosuppression. Cancer Cell 30(4):507–508

    Article  CAS  PubMed  Google Scholar 

  • Maciel-Barón LA, Morales-Rosales SL, Aquino-Cruz AA, Triana-Martínez F, Galván-Arzate S, Luna-López A et al (2016) Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli. Age (Dordr) 38(1):26

    Article  CAS  Google Scholar 

  • Maier KE, Levy M (2016) From selection hits to clinical leads: progress in aptamer discovery. Mol Ther Methods Clin Dev 5:16014

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McKeague M, Derosa MC (2012) Challenges and opportunities for small molecule aptamer development. J Nucleic Acids 2012:748913

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mirzayans R, Scott A, Cameron M, Murray D (2005) Induction of accelerated senescence by gamma radiation in human solid tumor-derived cell lines expressing wild-type TP53. Radiat Res 163(1):53–62

    Article  CAS  PubMed  Google Scholar 

  • Mosteiro L, Pantoja C, Alcazar N, Marión RM, Chondronasiou D, Rovira M et al (2016) Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science 354(6315):pii:aaf4445

    Google Scholar 

  • Muñoz-Espín D, Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15(7):482–496

    Article  PubMed  CAS  Google Scholar 

  • Muñoz-Espín D, Cañamero M, Maraver A, Gómez-López G, Contreras J, Murillo-Cuesta S et al (2013) Programmed cell senescence during mammalian embryonic development. Cell 155(5):1104–1118

    Article  PubMed  CAS  Google Scholar 

  • Muñoz-Espín D, Rovira M, Galiana I, Giménez C, Lozano-Torres B, Paez-Ribes M et al (2018) A versatile drug delivery system targeting senescent cells. EMBO Mol Med 10(9):pii:e9355

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Ng EW, Shima DT, Calias P, Cunningham ET Jr, Guyer DR, Adamis AP (2006) Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 5(2):123–132

    Article  CAS  PubMed  Google Scholar 

  • Ni S, Yao H, Wang L, Lu J, Jiang F, Lu A et al (2017) Chemical modifications of nucleic acid aptamers for therapeutic purposes. Int J Mol Sci 18(8):pii:E1683

    Google Scholar 

  • Novakova Z, Hubackova S, Kosar M, Janderova-Rossmeislova L, Dobrovolna J, Vasicova P et al (2010) Cytokine expression and signaling in drug-induced cellular senescence. Oncogene 29(2):273–284

    Article  CAS  PubMed  Google Scholar 

  • Pascal T, Debacq-Chainiaux F, Chrétien A, Bastin C, Dabée AF, Bertholet V et al (2005) Comparison of replicative senescence and stress-induced premature senescence combining differential display and low-density DNA arrays. FEBS Lett 579(17):3651–3659

    Article  CAS  PubMed  Google Scholar 

  • Pazolli E, Alspach E, Milczarek A, Prior J, Piwnica-Worms D, Stewart SA (2012) Chromatin remodeling underlies the senescence-associated secretory phenotype of tumor stromal fibroblasts that supports cancer progression. Cancer Res 72(9):2251–2261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perrott KM, Wiley CD, Desprez PY, Campisi J (2017) Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells. Geroscience 39(2):161–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pospelova TV, Demidenko ZN, Bukreeva EI, Pospelov VA, Gudkov AV, Blagosklonny MV (2009) Pseudo-DNA damage response in senescent cells. Cell Cycle 8(24):4112–4118

    Article  CAS  PubMed  Google Scholar 

  • Prodeus A, Sparkes A, Fischer NW, Cydzik M, Huang E, Khatri I et al (2018) A synthetic cross-species CD200R1 agonist suppresses inflammatory immune responses in vivo. Mol Ther Nucleic Acids 12:350–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Purcell M, Kruger A, Tainsky MA (2014) Gene expression profiling of replicative and induced senescence. Cell Cycle 13(24):3927–3937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ray P, Sullenger BA, White RR (2013) Further characterization of the target of a potential aptamer biomarker for pancreatic cancer: cyclophilin B and its posttranslational modifications. Nucleic Acid Ther 23(6):435–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reimann M, Lee S, Loddenkemper C, Dörr JR, Tabor V, Aichele P et al (2010) Tumor stroma-derived TGF-beta limits myc-driven lymphomagenesis via Suv39h1-dependent senescence. Cancer Cell 17(3):262–272

    Article  CAS  PubMed  Google Scholar 

  • Ritschka B, Storer M, Mas A, Heinzmann F, Ortells MC, Morton JP et al (2017) The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev 31(2):172–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberson RS, Kussick SJ, Vallieres E, Chen SY, Wu DY (2005) Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res 65(7):2795–2803

    Article  CAS  PubMed  Google Scholar 

  • Robinson JI, Baxter EW, Owen RL, Thomsen M, Tomlinson DC, Waterhouse MP et al (2018) Affimer proteins inhibit immune complex binding to FcγRIIIa with high specificity through competitive and allosteric modes of action. Proc Natl Acad Sci USA 115(1):E72–E81

    Article  CAS  PubMed  Google Scholar 

  • Rodier F, Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192(4):547–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roos CM, Zhang B, Palmer AK, Ogrodnik MB, Pirtskhalava T, Thalji NM et al (2016) Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell 15(5):973–977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rose CM, Hayes MJ, Stettler GR, Hickey SF, Axelrod TM, Giustini NP et al (2010) Capillary electrophoretic development of aptamers for a glycosylated VEGF peptide fragment. Analyst 35(11):2945–2951

    Article  CAS  Google Scholar 

  • Sagini K, Costanzi E, Emiliani C, Buratta S, Urbanelli L (2018) Extracellular vesicles as conveyors of membrane-derived bioactive lipids in immune system. Int J Mol Sci 19(4).pii:E1227

    Google Scholar 

  • Salama R, Sadaie M, Hoare M, Narita M (2014) Cellular senescence and its effector programs. Genes Dev 28(2):99–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samaraweera L, Adomako A, Rodriguez-Gabin A, McDaid HM (2017) A novel indication for panobinostat as a senolytic drug in NSCLC and HNSCC. Sci Rep 7(1):1900

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schafer MJ, White TA, Iijima K, Haak AJ, Ligresti G, Atkinson EJ et al (2017) Cellular senescence mediates fibrotic pulmonary disease. Nat Commun 8:14532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, Bonner WM, Barrett JC (2004) Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat Cell Biol 6(2):168–170

    Article  CAS  PubMed  Google Scholar 

  • Sefah K, Shangguan D, Xiong X, O’Donoghue MB, Tan W (2010) Development of DNA aptamers using Cell-SELEX. Nat Protoc 5(6):1169–1185

    Article  CAS  PubMed  Google Scholar 

  • Serrano M (2014) Senescence helps regeneration. Dev Cell 31(6):671–672

    Article  CAS  PubMed  Google Scholar 

  • Severino J, Allen RG, Balin S, Balin A, Cristofalo VJ (2000) Is beta-galactosidase staining a marker of senescence in vitro and in vivo? Exp Cell Res 257(1):162–171

    Article  CAS  PubMed  Google Scholar 

  • Shamah SM, Healy JM, Cload ST (2008) Complex target SELEX. Acc Chem Res 41(1):130–138

    Article  CAS  PubMed  Google Scholar 

  • Sidi R, Pasello G, Opitz I, Soltermann A, Tutic M, Rehrauer H et al (2011) Induction of senescence markers after neo-adjuvant chemotherapy of malignant pleural mesothelioma and association with clinical outcome: an exploratory analysis. Eur J Cancer 47(2):326–332

    Article  CAS  PubMed  Google Scholar 

  • Simeon R, Chen Z (2018) In vitro-engineered non-antibody protein therapeutics. Protein Cell 9(1):3–14

    Article  CAS  PubMed  Google Scholar 

  • Storer M, Mas A, Robert-Moreno A, Pecoraro M, Ortells MC, Di Giacomo V et al (2013) Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155(5):1119–1130

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Coppé JP, Lam EW (2018) Cellular senescence: the sought or the unwanted? Trends Mol Med 24(10):871–885

    Article  CAS  PubMed  Google Scholar 

  • Supiot S, Shubbar S, Fleshner N, Warde P, Hersey K, Wallace K et al (2008) A phase I trial of pre-operative radiotherapy for prostate cancer: clinical and translational studies. Radiother Oncol 88(1):53–60

    Article  PubMed  Google Scholar 

  • Takahashi A, Okada R, Nagao K, Kawamata Y, Hanyu A, Yoshimoto S et al (2017) Exosomes maintain cellular homeostasis by excreting harmful DNA from cells. Nat Commun 8:15287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takasugi M (2018) Emerging roles of extracellular vesicles in cellular senescence and aging. Aging Cell 17(2)

    Google Scholar 

  • Takasugi M, Okada R, Takahashi A, Virya Chen D, Watanabe S, Hara E (2017) Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2. Nat Commun 8:15729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang AA, Tiede C, Hughes DJ, McPherson MJ, Tomlinson DC (2017) Isolation of isoform-specific binding proteins (Affimers) by phage display using negative selection. Sci Signal 10(505):pii:eaan0868

    Google Scholar 

  • Tang H, Geng A, Zhang T, Wang C, Jiang Y, Mao Z (2019) Single senescent cell sequencing reveals heterogeneity in senescent cells induced by telomere erosion. Protein Cell 10(5):370–375

    Article  PubMed  Google Scholar 

  • Tasdemir N, Banito A, Roe JS, Alonso-Curbelo D, Camiolo M, Tschaharganeh DF et al (2016) BRD4 connects enhancer remodeling to senescence immune surveillance. Cancer Discov 6(6):612–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP (2002) DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 62(6):1876–1883

    Google Scholar 

  • Tiede C, Tang AA, Deacon SE, Mandal U, Nettleship JE, Owen RL et al (2014) Adhiron: a stable and versatile peptide display scaffold for molecular recognition applications. Protein Eng Des Sel 27(5):145–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tiede C, Bedford R, Heseltine SJ, Smith G, Wijetunga I, Ross R et al (2017) Affimer proteins are versatile and renewable affinity reagents. Elife 6:pii:e24903

    Google Scholar 

  • Toso A, Revandkar A, Di Mitri D, Guccini I, Proietti M, Sarti M et al (2014) Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep 9(1):75–89

    Article  CAS  PubMed  Google Scholar 

  • Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505–510

    Article  CAS  PubMed  Google Scholar 

  • Vandghanooni S, Eskandani M, Barar J, Omidi Y (2018) Recent advances in aptamer-armed multimodal theranostic nanosystems for imaging and targeted therapy of cancer. Eur J Pharm Sci 117:301–312

    Article  CAS  PubMed  Google Scholar 

  • Vanhooren V, Navarrete Santos A, Voutetakis K, Petropoulos I, Libert C, Simm A et al (2015) Protein modification and maintenance systems as biomarkers of ageing. Mech Ageing Dev 51:71–84

    Article  CAS  Google Scholar 

  • von Zglinicki T, Nilsson E, Döcke WD, Brunk UT (1995) Lipofuscin accumulation and ageing of fibroblasts. Gerontology 41(Suppl 2):95–108

    Article  Google Scholar 

  • Voutetakis K, Chatziioannou A, Gonos ES, Trougakos IP (2015) Comparative meta-analysis of transcriptomics data during cellular senescence and in vivo tissue ageing. Oxid Med Cell Longev 2015:732914

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wei W, Ji S (2018) Cellular senescence: molecular mechanisms and pathogenicity. J Cell Physiol 233(12):9121–9135

    Article  CAS  PubMed  Google Scholar 

  • White RR, Sullenger BA, Rusconi CP (2000) Developing aptamers into therapeutics. J Clin Invest 106(8):929–934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiley CD, Flynn JM, Morrissey C, Lebofsky R, Shuga J, Dong X et al (2017) Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence. Aging Cell 16(5):1043–1105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams BA, Lin L, Lindsay SM, Chaput JC (2009) Evolution of a histone H4-K16 acetyl-specific DNA aptamer. J Am Chem Soc 131(18):6330–6331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu PC, Wang Q, Grobman L, Chu E, Wu DY (2012) Accelerated cellular senescence in solid tumor therapy. Exp Oncol 34(3):298–305

    CAS  PubMed  Google Scholar 

  • Xu M, Tchkonia T, Ding H, Ogrodnik M, Lubbers ER, Pirtskhalava T et al (2015) JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc Natl Acad Sci USA 112(46):E6301–E6310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM et al (2018) Senolytics improve physical function and increase lifespan in old age. Nat Med 24(8):1246–1256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang NC, Hu ML (2005) The limitations and validities of senescence associated-beta-galactosidase activity as an aging marker for human foreskin fibroblast Hs68 cells. Exp Gerontol 40(10):813–819

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Fang J, Chen J (2017) Tumor cell senescence response produces aggressive variants. Cell Death Discov 3:17049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshida T, Akatsuka T, Imanaka-Yoshida K (2015) Tenascin-C and integrins in cancer. Cell Adh Migr 9(1–2):96–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M et al (2018) Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine 36:18–28

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu X, Yang YP, Dikici E, Deo SK, Daunert S (2017) Beyond antibodies as binding partners: the role of antibody mimetics in bioanalysis. Annu Rev Anal Chem (Palo Alto Calif) 10(1):293–320

    Article  CAS  Google Scholar 

  • Zhang H, Pan KH, Cohen SN (2003) Senescence-specific gene expression fingerprints reveal cell-type-dependent physical clustering of up-regulated chromosomal loci. Proc Natl Acad Sci USA 100(6):3251–3256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Kim MS, Jia B, Ya J, Zuniga-Hertz J P, Han C et al (2017). Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature 548(7665):52–57

    Google Scholar 

  • Zheng J, Zhao S, Yu X, Huang S, Liu HY (2017) Simultaneous targeting of CD44 and EpCAM with a bispecific aptamer effectively inhibits intraperitoneal ovarian cancer growth. Theranostics 7(5):1373–1388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou J, Rossi J (2017) Aptamers as targeted therapeutics: current potential and challenges. Nat Rev Drug Discov. 16(3):181–202

    Article  CAS  PubMed  Google Scholar 

  • Zhu Q, Liu G, Kai M (2015) DNA aptamers in the diagnosis and treatment of human diseases. Molecules 20(12):20979–20997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhuo Z, Yu Y, Wang M, Li J, Zhang Z, Liu J et al (2017) Recent Advances in SELEX Technology and Aptamer Applications in Biomedicine. Int J Mol Sci 18(10):pii:E2142

    Google Scholar 

Download references

Acknowledgements

We wish to thank Dr Darren Tomlinson and Dr Thomas A. Hughes (University of Leeds, UK) for introducing us to Affimers technology.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elvira Crescenzi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Leonardi, A., Pacifico, F., Crescenzi, E. (2020). Potential Applications of Aptamers for Targeting Senescent Cells. 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_10

Download citation

Publish with us

Policies and ethics