Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Advances in Therapy
Published in: Advances in Therapy 4/2020

Open Access 01-04-2020 | Review

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review

Authors: Mateo Amaya-Montoya, Agustín Pérez-Londoño, Valentina Guatibonza-García, Andrea Vargas-Villanueva, Carlos O. Mendivil

Published in: Advances in Therapy | Issue 4/2020

Login to get access

Abstract

Life expectancy has increased substantially over the last few decades, leading to a worldwide increase in the prevalence and burden of aging-associated diseases. Recent evidence has proven that cellular senescence contributes substantially to the development of these disorders. Cellular senescence is a state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype—SASP) that plays a physiological role in embryonic development and healing processes. However, DNA damage and oxidative stress that occur during aging cause the accumulation of senescent cells, which through their SASP bring about deleterious effects on multiple organ and systemic functions. Ablation of senescent cells through genetic or pharmacological means leads to improved life span and health span in animal models, and preliminary evidence suggests it may also have a positive impact on human health. Thus, strategies to reduce or eliminate the burden of senescent cells or their products have the potential to impact multiple clinical outcomes with a single intervention. In this review, we touch upon the basics of cell senescence and summarize the current state of development of therapies against cell senescence for human use.
Literature
1.
2.
Mason A, Lee R, Abrigo M, Lee SH. Support ratios and demographic dividens: estimates for the world. United Nations, Department of Economic and Social Affairs, Population Division. Technical paper no. 2017/1. New York; 2017.
3.
World Health Organization. World health statistics overview 2019: monitoring health for SDG, sustainable development goals. License: CC BY-NC-SA 3.0 IGO. Geneva; 2019.
4.
5.
Institute for Health and Evaluation (IHME). Findings from the global burden of disease study 2017. Seattle: IHME; 2018.
6.
7.
Shay JW, Wright WE. Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol. 2000;1:72–6.PubMed
8.
Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.PubMed
9.
Chen Q, Fischer A, Reagan JD, Yan LJ, Ames BN. Oxidative DNA damage and senescence of human diploid fibroblast cells. Proc Natl Acad Sci USA. 1995;92:4337–411.PubMedPubMedCentral
10.
Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997;88:593–602.PubMed
11.
Lowe SW, Cepero E, Evan G. Intrinsic tumour suppression. Nature. 2004;432:307–15.PubMed
12.
13.
Kang C. Senolytics and senostatics: a two-pronged approach to target cellular senescence for delaying aging and age-related diseases. Mol Cells. 2019;42:821–7.PubMedPubMedCentral
14.
Di Leonardo A, Linke SP, Clarkin K, et al. DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev. 1994;8:2540–51.PubMed
15.
Ogryzko VV, Hirai TH, Russanova VR, et al. Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent. Mol Cell Biol. 1996;16:5210–8.PubMedPubMedCentral
16.
Terzi MY, Izmirli M, Gogebakan B. The cell fate: senescence or quiescence. Mol Biol Rep. 2016;43:1213–20.PubMed
17.
Patel PL, Suram A, Mirani N, et al. Derepression of hTERT gene expression promotes escape from oncogene-induced cellular senescence. Proc Natl Acad Sci USA. 2016;113:E5024–E50335033.PubMedPubMedCentral
18.
Milanovic M, Fan DNY, Belenki D. Senescence-associated reprogramming promotes cancer stemness. Nature. 2018;553:96–100.PubMed
19.
Chen W, Kang J, Xia J, et al. p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts. Int J Mol Med. 2008;21:645–53.PubMed
20.
Childs BG, Baker DJ, Kirkland JL. Senescence and apoptosis: dueling or complementary cell fates? EMBO Rep. 2014;15:1139–53.PubMedPubMedCentral
21.
Myrianthopoulos V, Evangelou K, Vasileiou PVS, et al. Senescence and senotherapeutics: a new field in cancer therapy. Pharmacol Ther. 2019;193:31–49.PubMed
22.
Salotti J, Johnson PF. Regulation of senescence and the SASP by the transcription factor C/EBPβ. Exp Gerontol. 2019;128:110752.PubMed
23.
Da Silva-Álvarez S, Picallos-Rabina P, Antelo-Iglesias L. The development of cell senescence. Exp Gerontol. 2019;128:110742.PubMed
24.
Acosta JC, O'Loghlen A, Banito A, et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell. 2008;133:1006–188.PubMed
25.
Acosta JC, Banito A, Wuestefeld T, et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013;15:978–90.PubMedPubMedCentral
26.
Demaria M, Ohtani N, Youssef SA, et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell. 2014;31:722–33.PubMedPubMedCentral
27.
Mosteiro L, Pantoja C, Alcazar N, et al. Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science. 2016;354:aaf.4445.
28.
Storer M, Mas A, Robert-Moreno A, et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell. 2013;155:1119–30.PubMed
29.
Franceschi C, Bonafè M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.PubMed
30.
31.
Valenzuela CA, Quintanilla R, Moore-Carrasco R. The potential role of senescence as a modulator of platelets and tumorigenesis. Front Oncol. 2017;7:188.PubMedPubMedCentral
32.
Parrinello S, Coppe JP, Krtolica A, et al. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J Cell Sci. 2005;118:485–96.PubMed
33.
Angelini PD, Zacarias Fluck MF, Pedersen K, et al. Constitutive HER2 signaling promotes breast cancer metastasis through cellular senescence. Cancer Res. 2013;73:450–8.PubMed
34.
35.
36.
Faget DV, Ren Q, Stewart SA. Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer. 2019;19:439–53.PubMed
37.
Galbiati A, Beauséjour C, d’Adda di Fagagna F. A novel single-cell method provides direct evidence persistent DNA damage in senescent cells and aged mammalian tissues. Aging Cell. 2017;16:422–7.PubMedPubMedCentral
38.
39.
Rogakou E, Boon C, Redon C, et al. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 1999;146:905–15.PubMedPubMedCentral
40.
Sedelnikova OA, Horikawa I, Zimonjic DB, et al. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat Cell Biol. 2004;6:168–71.PubMed
41.
Alimonti A, Nardella C, Chen Z. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J Clin Investig. 2010;120:681–93.PubMedPubMedCentral
42.
Demidenko Z, Blagosklonny M. Growth stimulation leads to cellular senescence when the cell cycle is blocked. Cell Cycle. 2008;7:3355–61.PubMed
43.
Shenghui H, Sharpless N. Senescence in health and disease. Cell. 2017;169:1000–111.
44.
Pluquet O, Pourtier A, Abbadie C. The unfolded protein response and cellular senescence. A review in the theme: cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. Am J Physiol Cell Physiol. 2014;308:C415–C425425.PubMed
45.
Burton D, Faragher R. Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing. Biogerontology. 2018;19:447–59.PubMedPubMedCentral
46.
Minamino T, Orimo M, Shimizu I, et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med. 2009;15:1082–8.PubMed
47.
Higuchi M, Dusting G, Peshavariya H, et al. Differentiation of human adipose-derived stem cells into fat involves reactive oxygen species and forkhead box-O1 mediated upregulation of antioxidant enzymes. Stem Cells Dev. 2013;22:878–88.PubMed
48.
Dodig S, Cepelak I, Pavic I. Hallmarks of senescence and aging. Biochem Med (Zagreb). 2019;29:1–15.
49.
Muñoz-Espín D, Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol. 2014;15:482–96.PubMed
50.
Wang E, Gundersen D. Increased organization of cytoskeleton accompanying the aging of human fibroblasts in vitro. Exp Cell Res. 1984;154:191–202.PubMed
51.
Nishio K, Inoue A, Qiao S, et al. Senescence and cytoskeleton: overproduction of vimentin induces senescent-like morphology in human fibroblasts. Histochem Cell Biol. 2001;116:321–7.PubMed
52.
Ogrodnik M, Salmonowicz H, Jurk D. Expansion and cell-cycle arrest: common denominators of cellular senescence. Trends Biochem Sci. 2019;44:996–1008.PubMed
53.
Kurz DJ, Decary S, Hong Y, et al. Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci. 2000;113:3613–22.PubMed
54.
55.
Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Investig. 2011;121:3375–83.PubMedPubMedCentral
56.
Kuilman T, Michaloglou C, Vredeveld LC, et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell. 2008;133:1019–31.PubMed
57.
Kumar S, Millis AJ, Baglioni C. Expression of interleukin 1-inducible genes and production of interleukin 1 by aging human fibroblasts. Proc Natl Acad Sci USA. 1992;89:4683–7.PubMedPubMedCentral
58.
Orjalo AV, Bhaumik D, Gengler BK, et al. Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc Natl Acad Sci USA. 2009;106:17031–6.PubMedPubMedCentral
59.
Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000;12:121–7.PubMed
60.
Coppé JP, Desprez PY, Krtolica A, et al. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5:99–118.PubMedPubMedCentral
61.
Chen J, Mo R, Lescure PA, et al. Aging is associated with increased T-cell chemokine expression in C57BL/6 mice. J Gerontol A Biol Sci Med Sci. 2003;58:975–83.PubMed
62.
Sasaki M, Miyakoshi M, Sato Y, et al. Chemokine–chemokine receptor CCL2–CCR2 and CX3CL1–CX3CR1 axis may play a role in the aggravated inflammation in primary biliary cirrhosis. Dig Dis Sci. 2014;59:358–64.PubMed
63.
Bachstetter AD, Morganti JM, Jernberg J, et al. Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats. Neurobiol Aging. 2011;32:2030–44.PubMed
64.
Mecca C, Giambanco I, Donato R. Microglia and aging: the role of the TREM2–DAP12 and CX3CL1–CX3CR1 axes. Int J Mol Sci. 2018;19:E318.PubMed
65.
Pollak M. Insulin and insulin-like growth factor signaling in neoplasia. Nat Rev Cancer. 2008;8:915–28.PubMed
66.
Tran D, Bergholz J, Zhang H, et al. Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence. Aging Cell. 2014;13:669–78.PubMedPubMedCentral
67.
Lopes-Paciencia S, Saint-Germain E, Rowell MC, et al. The senescence-associated secretory phenotype and its regulation. Cytokine. 2019;117:15–22.PubMed
68.
Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15:786–801.PubMedPubMedCentral
69.
West MD, Pereira-Smith OM, Smith JR. Replicative senescence of human skin fibroblasts correlates with a loss of regulation and overexpression of collagenase activity. Exp Cell Res. 1989;184:138–47.PubMed
70.
Millis AJ, Hoyle M, McCue HM, et al. Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. Exp Cell Res. 1992;201:373–9.PubMed
71.
Hassona Y, Cirillo N, Prime HK, et al. Senescent cancer-associated fibroblasts secrete active MMP-2 that promotes keratinocyte dis-cohesion and invasion. Br J Cancer. 2014;111:1230–7.PubMedPubMedCentral
72.
Özcan S, Alessio N, Acar MB, et al. Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses. Aging (Albany NY). 2016;8:1316–29.
73.
Zeng G, Millis AJ. Differential regulation of collagenase and stromelysin mRNA in late passage cultures of human fibroblasts. Exp Cell Res. 1996;222:150–6.PubMed
74.
Quillard T, Araújo HA, Franck G. Matrix metalloproteinase-13 predominates over matrix metalloproteinase-8 as the functional interstitial collagenase in mouse atheromata. Arterioscler Thromb Vasc Biol. 2014;34:1179–86.PubMedPubMedCentral
75.
McQuibban GA, Gong JH, Wong JP. Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood. 2002;100:1160–7.PubMed
76.
Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018;28:436–56.PubMed
77.
78.
Karimian A, Ahmadi Y, Yousefi B. Multiple functions of P21 in cell cycle, apoptosis and transcriptional regulation after DNA damage. DNA Repair (Amst). 2016;42:63–71.
79.
80.
Kobbe V. Cellular senescence: a view throughout organismal life. Cell Mol Life Sci. 2018;75:3553–677.
81.
Muñoz-Espín D, Cañamero M, Maraver A, et al. Programmed cell senescence during mammalian embryonic development. Cell. 2013;155:1104–18.PubMed
82.
Vicente R, Mausset-Bonnefont A, Jorgensen C, et al. Cellular senescence impact on immune cell fate and function. Aging Cell. 2016;15:400–6.PubMedPubMedCentral
83.
Rajagopalan S. HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction. Cell Mol Immunol. 2014;11:460–6.PubMedPubMedCentral
84.
Rajagopalan S, Long E. Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling. Proc Natl Acad Sci USA. 2012;109:20596–601.PubMedPubMedCentral
85.
Stein GH, Drullinger LF, Soulard A, et al. Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol. 1999;19:2109–17.PubMedPubMedCentral
86.
Jun J-I, Lau L. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol. 2010;12:676–94.PubMedPubMedCentral
87.
Baker D, Wijshake T, Tchkonia T. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479:232–7.PubMedPubMedCentral
88.
Childs B, Baker D, Wijshake T. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016;354:472–7.PubMedPubMedCentral
89.
Pal A, Potjer T, Thomsen S, et al. Loss of function mutations in the cell-cycle control gene CDKN2A impact on glucose homeostasis in humans. Diabetes. 2016;65:527–33.PubMed
90.
González-Navarro H, Vinue A, Sanz MJ, et al. Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging. Aging Cell. 2013;12:102–11.PubMed
91.
Demaria M, O’Leary MN, Chang J, et al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov. 2017;7:165–76.PubMed
92.
Calcinotto A, Kohli J, Zagato E, et al. Cellular senescence: aging, cancer, and injury. Physiol Rev. 2019;99:1047–78.PubMed
93.
Bhat R, Crowe E, Bitto A, et al. Astrocyte senescence as a component of Alzheimer’s disease. PLoS One. 2012;7:e45069.PubMedPubMedCentral
94.
Chinta SJ, Woods G, Demaria M, et al. Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to Parkinson’s disease. Cell Rep. 2017;22:930–40.
95.
Courtois-Cox S, Jones SL, Cichowski K. Many roads lead to oncogene-induced senescence. Oncogene. 2008;27:2801–9.PubMed
96.
Childs BG, Gluscevic M, Baker DJ, et al. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017;16:718–35.PubMedPubMedCentral
97.
Trujillo M, Pajvani U, Scherer P. Apoptosis through targeted activation of caspase (“ATTAC-mice”): novel mouse models of inducible and reversible tissue ablation. Cell Cycle. 2005;4:1141–5.PubMed
98.
Clackson T, Yang W, Rozamus L. Redesigning an FKBP–ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci USA. 1998;95:10437–42.PubMedPubMedCentral
99.
Wang W, Wu J, Zhang Z, Tong T. Characterization of regulatory elements on the promoter region of p16INK4a that contribute to overexpression of p16 in senescent fibroblasts. J Biol Chem. 2001;276:48655–61.PubMed
100.
Baker DJ, Childs B, Durik M, et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature. 2016;530:184–8.PubMedPubMedCentral
101.
Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14:644–58.PubMedPubMedCentral
102.
Chang Q, Jorgensen C, Pawson T. Hedley DW Effects of dasatinib on EphA2 receptor tyrosine kinase activity and downstream signalling in pancreatic cancer. Br J Cancer. 2008;99:1074–82.PubMedPubMedCentral
103.
Boly R, Gras T, Lamkami T, et al. Quercetin inhibits a large panel of kinases implicated in cell biology. Int J Oncol. 2011;38:833–42.PubMed
104.
Wang C, Maddick M, Miwa S, et al. Adult-onset, short-term dietary restriction reduces cell senescence in mice. Aging (Albany NY). 2010;2:555–66.
105.
Fontana L, Mitchell SE, Wang B, et al. The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon. Aging Cell. 2018;17:e12746.PubMedPubMedCentral
106.
Ogrodnik M, Miwa S, Tchkonia T, et al. Cellular senescence drives age-dependent hepatic steatosis. Nat Commun. 2017;8:15691.PubMedPubMedCentral
107.
Jurk D, Wang C, Miwa S, et al. Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell. 2012;11:996–1004.PubMed
108.
Fontana L, Nehme J, Demaria M. Caloric restriction and cellular senescence. Mech Ageing Dev. 2018;176:19–23.PubMed
109.
Fontana L, Villareal DT, Das SK, et al. Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial. Aging Cell. 2016;15:22–7.PubMed
110.
Moiseeva O, Deschênes-Simard X, St-Germain E, et al. Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation. Aging Cell. 2013;12:489–98.PubMed
111.
Campbell JM, Bellman SM, Stephenson MD, et al. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. Ageing Res Rev. 2017;40:31–44.PubMed
112.
Wang R, Yu Z, Sunchu B, Shoaf J, et al. Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism. Aging Cell. 2017;16:564–74.PubMedPubMedCentral
113.
Gurău F, Baldoni S, Prattichizzo F, et al. Anti-senescence compounds: a potential nutraceutical approach to healthy aging. Ageing Res Rev. 2018;46:14–311.PubMed
114.
Xu M, Tchkonia T, Ding H, et al. JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc Natl Acad Sci USA. 2015;112:E6301–E63106310.PubMedPubMedCentral
115.
Roskoski R Jr. Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases. Pharmacol Res. 2016;111:784–803.PubMed
116.
Palmer AK, Xu M, Zhu Y, et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell. 2019;18:e12950.PubMedPubMedCentral
117.
Xu M, Pirtskhalava T, Farr JN, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24:1246–56.PubMedPubMedCentral
118.
Hickson LJ, Langhi Prata LGP, Bobart SA, et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019;47:446–56.PubMedPubMedCentral
119.
Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 2016;15:428–35.PubMedPubMedCentral
120.
Chang J, Wang Y, Shao L, et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med. 2016;22:78–83.PubMed
121.
Fuhrmann-Stroissnigg H, Ling YY, Zhao J, et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nat Commun. 2017;8:422.PubMedPubMedCentral
122.
123.
Baar MP, Brandt RM, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell. 2017;169:132–47.PubMedPubMedCentral
124.
Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18–28.PubMedPubMedCentral
125.
Prata LGPL, Ovsyannikova IG, Tchkonia T, Kirkland JL. Senescent cell clearance by the immune system: emerging therapeutic opportunities. Semin Immunol. 2018;40:101275.PubMed
126.
Khosla S, Farr JN, Kirkland JL. Inhibiting cellular senescence: a new therapeutic paradigm for age-related osteoporosis. J Clin Endocrinol Metab. 2018;103:1282–90.PubMedPubMedCentral
127.
Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019;571:183–92.PubMedPubMedCentral
128.
Sikora E, Bielak-Zmijewska A, Mosieniak G. Targeting normal and cancer senescent cells as a strategy of senotherapy. Ageing Res Rev. 2019;55:100941.PubMed
Metadata
Title
Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review
Authors
Mateo Amaya-Montoya
Agustín Pérez-Londoño
Valentina Guatibonza-García
Andrea Vargas-Villanueva
Carlos O. Mendivil
Publication date
01-04-2020
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 4/2020
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-020-01287-0

Other articles of this Issue 4/2020

Advances in Therapy 4/2020 Go to the issue

Original Research

HER2-Positive Metastatic Breast Cancer: A Retrospective Cohort Study of Healthcare Costs in the Targeted-Therapy Age

Original Research

Efficacy of Zotarolimus-Eluting Stents in Treating Diabetic Coronary Lesions: An Optical Coherence Tomography Study

Original Research

New Therapeutic Strategy and Innovative Lubricating Ophthalmic Solution in Minimizing Dry Eye Disease Associated with Cataract Surgery: A Randomized, Prospective Study

Study Protocol

Efficacy and Safety of Basal Insulin-Based Treatment Versus Twice-Daily Premixed Insulin After Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus in China: Study Protocol for a Randomized Controlled Trial (BEYOND V)

Original Research

Use of Acellular Dermal Matrix for Urethroplasty Coverage in Proximal Hypospadias Repair: a Pilot Study

Review

Perioperative Antibiotics in Clean-Contaminated Head and Neck Surgery: A Systematic Review and Meta-Analysis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits