La senescencia celular es un fenómeno que tradicionalmente se ha caracterizado por la detención de la proliferación de células post-mitóticas como respuesta a algún tipo de daño. Ahora se sabe que las células senescentes secretan un conjunto de moléculas, entre las que se encuentran quimiocinas, citocinas, factores de crecimiento y otras que, en conjunto, han sido denominadas fenotipo secretor asociado a la senescencia (SASP). Estas moléculas pueden tener efectos benéficos o dañinos sobre las células vecinas a ellas. Esta revisión describe dichos efectos, así como la relación del SASP con diversas enfermedades asociadas a la edad. También se analiza el rumbo que han tomado las investigaciones recientes para tratar de modular o eliminar el efecto del SASP en dichas patologías.
Rodier F, Campisi J. Four faces of cellular senescence. J Cell Biol. 2011;192(4):547-56.
Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961 Dec;25: 585-621.
Muller M. Cellular senescence: molecular mechanisms, in vivo significance, and redox considerations. Antioxid Redox Signal. 2009;11(1):59-98.
Cristofalo VJ, Lorenzini A, Allen RG, Torres C, Tresini M. Replicative senescence: a critical review. Mech Ageing Dev. 2004;125(10-11):827-48.
Toussaint O, Medrano EE, von Zglinicki T. Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp Gerontol. 2000;35(8): 927-45.
Torres C, Lewis L, Cristofalo VJ. Proteasome inhibitors shorten replicative life span and induce a senescent-like phenotype of human fibroblasts. J Cell Physiol. 2006;207(3):845-53.
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A. 1995;92(20):9363-7.
Storer M, Mas A, Robert-Moreno A, Pecoraro M, Ortells MC, Di Giacomo V, et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell. 2013;155(5):1119-30.
Beauséjour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, et al. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J. 2003;22(16):4212-22.
Maya-Mendoza A, Merchut-Maya JM, Bartkova J, Bartek J, Streuli CH, Jackson DA. Immortalised breast epithelia survive prolonged DNA replication stress and return to cycle from a senescent-like state. Cell Death Dis. 2014;5e1351.
Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 2010; 16(5):238-46.
Coppe JP, Patil CK, Rodier F, Krtolica A, Beauséjour CM, Parrinello S, et al. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS One. 2010;5(2):e9188.
Bhat R, Crowe EP, Bitto A, Moh M, Katsetos CD, Garcia FU, et al. Astrocyte senescence as a component of Alzheimer’s disease. PLoS One. 2012;7(9): e45069.
Muñoz-Espín D, Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Bio. 2014;15(7):482-96.
Jiménez-Salazar JE, González-Nuñez L, Königsberg-Fainstein M, Gómez-Quiroz LE, Zentella-Dehesa A, Damián-Matsumura P. Estructura y función de las uniones estrechas en la transición epitelio-mesénquima (TEM) y la tumorigénesis del cáncer de mama humano. REB. 2012;31(2):49-59.
Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178-96.
Coppe JP, Kauser K, Campisi J, Beauséjour CM. Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence. J Biol Chem. 2006;281(40):29568-74.
Loaiza N, Demaria M. Cellular senescence and tumor promotion: Is aging the key? Biochim Biophys Acta. 2016;1865(2):155-67.
Nickoloff BJ, Lingen MW, Chang BD, Shen M, Swift M, Curry J, et al. Tumor suppressor maspin is up-regulated during keratinocyte senescence, exerting a paracrine antiangiogenic activity. Cancer Res. 2004;64(9):2956-61.
Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell. 2008;132(3):363-74.
Kawata H, Kamiakito T, Nakaya T, Komatsubara M, Komatsu K, Morita T, et al. Stimulation of cellular senescent processes, including secretory phenotypes and anti-oxidant responses, after androgen deprivation therapy in human prostate cancer. J Steroid Biochem Mol Biol. 2017 Jan;165(Pt B):219-27.
Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479(7372):232-6.
Magistretti PJ. Neuron-glia metabolic coupling and plasticity. J Exp Biol. 2006;209(Pt 12):2304-11.
Chinta SJ, Woods G, Rane A, Demaria M, Campisi J, Andersen JK. Cellular senescence and the aging brain. Exp Gerontol. 2015;683-7.
Kim JS, Kosek DJ, Petrella JK, Cross JM, Bamman MM. Resting and load-induced levels of myogenic gene transcripts differ between older adults with demonstrable sarcopenia and young men and women. J Appl Physiol. 2005;99(6):2149-58.
Sousa-Victor P, Gutarra S, Garcia-Prat L, Rodriguez-Ubreva J, Ortet L, Ruiz-Bonilla V, et al. Geriatric muscle stem cells switch reversible quiescence into senescence. Nature. 2014 Feb 20;506(7488): 316-21.
Nieto-Vazquez I, Fernandez-Veledo S, de Alvaro C, Lorenzo M. Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle. Diabetes. 2008;57(12):3211-21.
Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, et al. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature. 2006;443(7110):453-7.
Kim YJ, Hwang SH, Lee SY, Shin KK, Cho HH, Bae YC et al. miR-486-5p Induces Replicative Senescence of Human Adipose Tissue-Derived Mesenchymal Stem Cells and Its Expression Is Controlled by High Glucose. Stem Cells Dev. 2012;21(10):1749-60.
Rippe C, Blimline M, Magerko KA, Lawson BR, LaRocca TJ, Donato AJ, et al. MicroRNA changes in human arterial endothelial cells with senescence: relation to apoptosis, eNOS and inflammation. Exp Gerontol. 2012;47(1):45-51.
Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R. Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol. 2010;30(7):1282-92.
Laberge RM, Zhou L, Sarantos MR, Rodier F, Freund A, de Keizer PL, et al. Glucocorticoids suppress selected components of the senescence-associated secretory phenotype. Aging Cell. 2012;11(4):569-78.
Moiseeva O, Deschenes-Simard X, St-Germain E, Igelmann S, Huot G, Cadar AE, et al. Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-kappaB activation. Aging Cell. 2013;12(3):489-98.
Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, et al. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol. 2015;17 (8):1049-61.
Kirkland JL, Tchkonia T. Clinical strategies and animal models for developing senolytic agents. Exp Gerontol. 2015;6819-25.