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4 - The Connection between Cellular Senescence and Age-Related Diseases

from Part I - Biomedical Aspects

Published online by Cambridge University Press:  10 January 2019

By
Claire Falandry
Edited by
Rocío Fernández-Ballesteros ,
Athanase Benetos  and
Jean-Marie Robine
Rocío Fernández-Ballesteros
Affiliation:
Universidad Autónoma de Madrid
Athanase Benetos
Affiliation:
Université de Lorraine and Institut national de la santé et de la recherche médicale (INSERM) Nancy
Jean-Marie Robine
Affiliation:
INSERM
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Summary

Age is associated with a progressive decline in the functional reserve of multiple organ systems and, at the molecular and cellular level, with the accumulation of mutations. Cumulative evidence has demonstrated that senescence contributes both to tissue exhaustion as well as diseases associated with aging. This article seeks at answering to the simple following questions, on the basis on current knowledge and recent findings coming from basic and translational research: (i) why do somatic cells have to senesce?; (ii) how to define cell senescence(s)?; (iii) how senescence is activated?; (iv) what are the phenotypic changes are induced by senescence?; (v) what are the relationships between senescence and the longevity pathways? and (vi) what are the relationships between senescence and age-related diseases? In this last section, a special attention is paid to the more frequent age-related diseases: osteoporosis, neurodegenerative diseases, atherosclerosis, type 2 diabetes, cataract, respiratory diseases and cancer.
Type
Chapter
Information
The Cambridge Handbook of Successful Aging , pp. 41 - 52
Publisher: Cambridge University Press
Print publication year: 2019

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References

Acosta, J. C., Banito, A., Wuestefeld, T., et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. août 2013; 15(8): 978–90.CrossRefGoogle ScholarPubMed
Aguilaniu, H., Gustafsson, L., Rigoulet, M., and Nyström, T. Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science. 14 mars 2003; 299(5613): 1751–3.CrossRefGoogle ScholarPubMed
Akiyama, H., Barger, S., Barnum, S., et al. Inflammation and Alzheimer's disease. Neurobiol Aging. 1 mai 2000; 21(3): 383–421.CrossRefGoogle ScholarPubMed
Aoshiba, K., Nagai, A. Senescence hypothesis for the pathogenetic mechanism of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 1 déc 2009; 6(7): 596–601.CrossRefGoogle ScholarPubMed
Asbell, P. A., Dualan, I., Mindel, J., et al. Age-related cataract. The Lancet. 12 févr 2005; 365(9459): 599–609.CrossRefGoogle ScholarPubMed
Babizhayev, M. A., Vishnyakova, K. S., Yegorov, Y. E. Telomere-dependent senescent phenotype of lens epithelial cells as a biological marker of aging and cataractogenesis: the role of oxidative stress intensity and specific mechanism of phospholipid hydroperoxide toxicity in lens and aqueous. Fundam Clin Pharmacol. 1 avr 2011; 25(2): 139–62.CrossRefGoogle ScholarPubMed
Baker, D. J., Jeganathan, K. B., Malureanu, L., et al. Early aging-associated phenotypes in Bub3/Rae1 haplo insufficient mice. J Cell Biol. 13 févr 2006; 172(4): 529–40.CrossRefGoogle Scholar
Baker, D. J., Weaver, R. L., van Deursen, J. M. p21 both attenuates and drives senescence and aging in BubR1 progeroid mice. Cell Rep. 25 avr 2013; 3(4): 1164–74.CrossRefGoogle ScholarPubMed
Baker, D. J., Wijshake, T., Tchkonia, T., et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2 nov 2011; 479(7372): 232–6.CrossRefGoogle ScholarPubMed
Baxter, M. A., Wynn, R. F., Jowitt, S. N., et al. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells. 1 sept 2004; 22(5): 675–82.CrossRefGoogle ScholarPubMed
Benisch, P., Schilling, T., Klein-Hitpass, L., et al. The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PLoS ONE. 24 sept 2012; 7(9): e45142.CrossRefGoogle ScholarPubMed
Bhat, R., Crowe, E. P., Bitto, A., et al. Astrocyte senescence as a component of Alzheimer's disease. PLoS ONE. 12 sept 2012; 7(9): e45069.CrossRefGoogle ScholarPubMed
Bitto, A., Sell, C., Crowe, E., et al. Stress-induced senescence in human and rodent astrocytes. Exp Cell Res. 15 oct 2010; 316(17): 2961–8.CrossRefGoogle ScholarPubMed
Blagosklonny, M. V. Revisiting the antagonistic pleiotropy theory of aging: TOR-driven program and quasi-program. Cell Cycle. 15 août 2010; 9(16): 3171–6.CrossRefGoogle ScholarPubMed
Blagosklonny, M. V. Answering the ultimate question What is the Proximal Cause of Aging? Aging. 30 déc 2012; 4(12): 861–77.CrossRefGoogle ScholarPubMed
Borie, R., Tabèze, L., Thabut, G., et al. Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis. Eur Respir J. 1 déc 2016; 48(6): 1721–31.CrossRefGoogle ScholarPubMed
Campisi, J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 25 févr 2005; 120(4): 513–22.CrossRefGoogle ScholarPubMed
Campisi, J. Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol. 1 nov 2001; 11(11): S27–31.CrossRefGoogle ScholarPubMed
Campisi, J., Andersen, J. K., Kapahi, P., Melov, S. Cellular senescence: a link between cancer and age-related degenerative disease? Semin Cancer Biol. déc 2011; 21(6): 354–9.Google ScholarPubMed
Chen, H.-Z., Wang, F., Gao, P., et al. Age-associated Sirtuin 1 reduction in vascular smooth muscle links vascular senescence and inflammation to abdominal aortic aneurysm novelty and significance. Circ Res. 28 oct 2016; 119(10): 1076–88.CrossRefGoogle Scholar
Chen, J., Brodsky, S. V., Goligorsky, D. M., et al. Glycated collagen I induces premature senescence-like phenotypic changes in endothelial cells. Circ Res. 28 juin 2002; 90(12): 1290–8.CrossRefGoogle ScholarPubMed
Chen, Q., Liu, K., Robinson, A. R., et al. DNA damage drives accelerated bone aging via an NF-κB-dependent mechanism. J Bone Miner Res. 1 mai 2013; 28(5): 1214–28.CrossRefGoogle ScholarPubMed
Collado, M., Serrano, M. Senescence in tumours: evidence from mice and humans. Nat Rev Cancer. janv 2010; 10(1): 51–7.CrossRefGoogle ScholarPubMed
Coppé, J.-P., Patil, C. K., Rodier, F., et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. déc 2008; 6(12): e301.CrossRefGoogle ScholarPubMed
Falandry, C., Bonnefoy, M., Freyer, G., Gilson, E. Biology of cancer and aging: a complex association with cellular senescence. J Clin Oncol. 20 août 2014; 32(24): 2604–10.CrossRefGoogle ScholarPubMed
Gosselin, K., Martien, S., Pourtier, A., et al. Senescence-associated oxidative DNA damage promotes the generation of neoplastic cells. Cancer Res. 15 oct 2009; 69(20): 7917–25.CrossRefGoogle ScholarPubMed
Harman, D. Aging: a theory based on free radical and radiation chemistry. Journal of Gerontology. juill 1956; 11(3): 298–300.CrossRefGoogle ScholarPubMed
Hayflick, L., Moorhead, P. S. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961; 25: 585–621.CrossRefGoogle ScholarPubMed
Hoare, M., Ito, Y., Kang, T.-W., et al. NOTCH1 mediates a switch between two distinct secretomes during senescence. Nat Cell Biol. sept 2016; 18(9): 979–92.CrossRefGoogle ScholarPubMed
Hoare, M., Narita, M. Transmitting senescence to the cell neighbourhood. Nat Cell Biol. août 2013; 15(8): 887–9.CrossRefGoogle Scholar
Hsiao, R., Sharma, H. W., Ramakrishnan, S., Keith, E., Narayanan, R. Telomerase activity in normal human endothelial cells. Anticancer Res. avr 1997; 17(2A): 827–32.Google ScholarPubMed
Hubackova, S., Krejcikova, K., Bartek, J., Hodny, Z. IL1- and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine “Bystander senescence.” Aging. 30 déc 2012; 4(12): 932–51.CrossRefGoogle ScholarPubMed
Kang, T.-W., Yevsa, T., Woller, N., et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature. 24 nov 2011; 479(7374): 547–51.CrossRefGoogle ScholarPubMed
Kassem, M., Marie, P. J. Senescence-associated intrinsic mechanisms of osteoblast dysfunctions. Aging Cell. 1 avr 2011; 10(2): 191–7.CrossRefGoogle ScholarPubMed
Kirkwood, T. B., Holliday, R. The evolution of ageing and longevity. Proc R Soc Lond B Biol Sci. 21 sept 1979; 205(1161): 531–46.Google ScholarPubMed
Kitada, M., Ogura, Y., Koya, D. The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. Aging. 15 oct 2016; 8(10): 2290–307.CrossRefGoogle ScholarPubMed
Krizhanovsky, V., Yon, M., Dickins, R. A., et al. Senescence of activated stellate cells limits liver fibrosis. Cell. 22 août 2008; 134(4): 657–67.CrossRefGoogle ScholarPubMed
Krtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y.,Campisi, J. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci. 10 sept 2001; 98(21): 12072–7.CrossRefGoogle ScholarPubMed
Kuwano, K., Araya, J., Hara, H., et al. Cellular senescence and autophagy in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Respir Investig. 1 nov 2016; 54(6): 397–406.CrossRefGoogle ScholarPubMed
Lambers, C., Hacker, S., Posch, M., et al. T cell senescence and contraction of T cell repertoire diversity in patients with chronic obstructive pulmonary disease. Clin Exp Immunol. 1 mars 2009; 155(3): 466–75.CrossRefGoogle ScholarPubMed
Maier, J. A. M., Barenghi, L., Bradamante, S., Pagani, F. Induction of human endothelial cell growth by mildly oxidized low density lipoprotein. Atherosclerosis. 1 juin 1996; 123(1): 115–21.CrossRefGoogle ScholarPubMed
Markowski, D. N., Thies, H. W., Gottlieb, A., et al. HMGA2 expression in white adipose tissue linking cellular senescence with diabetes. Genes Nutr. 1 sept 2013; 8(5): 449–56.CrossRefGoogle ScholarPubMed
Matsushita, H., Chang, E., Glassford, A. J., et al. eNOS activity is reduced in senescent human endothelial cells. Circ Res. 26 oct 2001; 89(9): 793–8.CrossRefGoogle ScholarPubMed
Medawar, P. B. Unsolved Problems of Biology. London: H.K. Lewis; 1952.Google Scholar
Minagawa, S., Araya, J., Numata, T., et al. Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells. Am J Physiol – Lung Cell Mol Physiol. 1 mars 2011; 300(3): L391–401.CrossRefGoogle ScholarPubMed
Minamino, T., Komuro, I. Vascular cell senescence. Circ Res. 5 janv 2007; 100(1): 15–26.CrossRefGoogle ScholarPubMed
Minamino, T., Mitsialis, S. A., Kourembanas, S. Hypoxia extends the life span of vascular smooth muscle cells through telomerase activation. Mol Cell Biol. mai 2001; 21(10): 3336–42.CrossRefGoogle ScholarPubMed
Minamino, T., Miyauchi, H., Yoshida, T., et al. Endothelial cell senescence in human atherosclerosis. Circulation. 2 avr 2002; 105(13): 1541–4.CrossRefGoogle ScholarPubMed
Mitri, D. D., Alimonti, A. Non-cell-autonomous regulation of cellular senescence in cancer. Trends Cell Biol. 1 mars 2016; 26(3): 215–26.CrossRefGoogle ScholarPubMed
Perry, V. H., Nicoll, J. A. R., Holmes, C. Microglia in neurodegenerative disease. Nat Rev Neurol. avr 2010; 6(4): 193–201.CrossRefGoogle ScholarPubMed
Prieur, A., Peeper, D. S. Cellular senescence in vivo: a barrier to tumorigenesis. Curr Opin Cell Biol. avr 2008; 20(2): 150–5.CrossRefGoogle ScholarPubMed
Saeed, H., Abdallah, B. M., Ditzel, N., et al. Telomerase-deficient mice exhibit bone loss owing to defects in osteoblasts and increased osteoclastogenesis by inflammatory microenvironment. J Bone Miner Res. 1 juill 2011; 26(7): 1494–505.CrossRefGoogle ScholarPubMed
Salminen, A., Ojala, J., Kaarniranta, K., et al. Astrocytes in the aging brain express characteristics of senescence-associated secretory phenotype. Eur J Neurosci. 1 juill 2011; 34(1): 3–11.CrossRefGoogle ScholarPubMed
Schott, J. M., Revesz, T. Inflammation in Alzheimer's disease: insights from immunotherapy. Brain. 1 sept 2013; 136(9): 2654–6.CrossRefGoogle ScholarPubMed
Shi, S., Gronthos, S., Chen, S., et al. Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nat Biotechnol. juin 2002; 20(6): 587–91.CrossRefGoogle ScholarPubMed
Stout, M. B., Tchkonia, T., Pirtskhalava, T., et al. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging. 20 juill 2014; 6(7): 575–86.CrossRefGoogle ScholarPubMed
Tsuji, T., Aoshiba, K., Nagai, A. Alveolar cell senescence exacerbates pulmonary inflammation in patients with chronic obstructive pulmonary disease. Respir Int Rev Thorac Dis. 2010; 80(1): 59–70.Google ScholarPubMed
Tyner, S. D., Venkatachalam, S., Choi, J., et al. p53 mutant mice that display early ageing-associated phenotypes. Nature. 3 janv 2002; 415(6867): 45–53.CrossRefGoogle ScholarPubMed
Wang, J., Uryga, A. K., Reinhold, J., et al. Vascular smooth muscle cell senescence promotes atherosclerosis and features of plaque vulnerability: clinical perspective. Circulation. 17 nov 2015; 132(20): 1909–19.Google Scholar
Williams, G. C. Pleiotropy, natural selection, and the evolution of senescence. Evolution. 1957; 11: 398–411.CrossRefGoogle Scholar
Xu, S., Cai, Y., Wei, Y., et al. mTOR signaling from cellular senescence to organismal aging. Aging Dis. 4 nov 2014; 5(4): 263–73.Google ScholarPubMed
Xue, W., Zender, L., Miething, C., et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature. 8 févr 2007; 445(7128): 656–60.CrossRefGoogle ScholarPubMed
Yudoh, K., Nishioka, K. Telomerized presenescent osteoblasts prevent bone mass loss in vivo. Gene Ther. 1 avr 2004; 11(11): 909–15.CrossRefGoogle ScholarPubMed
Zhou, S., Greenberger, J. S., Epperly, M. W., et al. Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell. 1 juin 2008; 7(3): 335–43.CrossRefGoogle ScholarPubMed

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