Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia
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Summary: Cellular senescence is an age‐associated phenomenon that promotes tumor invasiveness owing to the secretion of proinflammatory cytokines, proteases, and growth factors. Herein we demonstrate that cellular senescence also potentially increases susceptibility to bacterial pneumonia caused by Streptococcus pneumoniae (the pneumococcus), the leading cause of infectious death in the elderly. Aged mice had increased lung inflammation as determined by cytokine analysis and histopathology of lung sections. Immunoblotting for p16, pRb, and mH2A showed that elderly humans and aged mice had increased levels of these senescence markers in their lungs vs. young controls. Keratin 10 (K10), laminin receptor (LR), and platelet‐activating factor receptor (PAFr), host proteins known to be co‐opted for bacterial adhesion, were also increased. Aged mice were found to be highly susceptible to pneumococcal challenge in a PsrP, the pneumococcal adhesin that binds K10, dependent manner. In vitro senescent A549 lung epithelial cells had elevated K10 and LR protein levels and were up to 5‐fold more permissive for bacterial adhesion. Additionally, exposure of normal cells to conditioned media from senescent cells doubled PAFr levels and pneumococcal adherence. Genotoxic stress induced by bleomycin and oxidative stress enhanced susceptibility of young mice to pneumonia and was positively correlated with enhanced p16, inflammation, and LR levels. These findings suggest that cellular senescence facilitates bacterial adhesion to cells in the lungs and provides an additional molecular mechanism for the increased incidence of community‐acquired pneumonia in the elderly. This study is the first to suggest a second negative consequence for the senescence‐associated secretory phenotype.
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Age-associated changes in genomic instability, telomere shortening, epigenetic alterations, cellular senescence, impaired autophagy, and mitochondrial dysfunction may promote IPF development and progression.
“Further, age-associated changes in genomic instability, telomere shortening, epigenetic alterations, cellular senescence, impaired autophagy, and mitochondrial dysfunction may promote IPF development and progression (3, 12, 62, 84, 88, 89, 116, 145).”
From Aging and Lung Disease (2020) · cites this paper as [62]
Bacteria, especially Streptococcus pneumoniae, are the most common pathogens that commonly cause CAP in the elderly.
“Bacteria, especially Streptococcus pneumoniae, are the most common pathogens that commonly cause CAP in the elderly (62).”
From Aging and Lung Disease (2020) · cites this paper as [62]
Age-associated alterations in immune surveillance, specifically decreased innate and adaptive immune responses, and dysfunctional immune response regulation can be responsible for increased lung pathology in response to infectious stimuli.
“Age-associated alterations in immune surveillance, specifically decreased innate and adaptive immune responses, and dysfunctional immune response regulation can be responsible for increased lung pathology in response to infectious stimuli (3, 62, 106, 110, 114, 135).”
From Aging and Lung Disease (2020) · cites this paper as [62]
Upregulation of epithelial cell surface receptors in response to chronic inflammation increases bacterial adhesion and accumulation in the aged lung and correlates with susceptibility to pneumonia.
“Upregulation of epithelial cell surface receptors in response to chronic inflammation increases bacterial adhesion and accumulation in the aged lung and correlates with susceptibility to pneumonia (62, 97).”
From Aging and Lung Disease (2020) · cites this paper as [62]
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Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Lopez, A. D., Mathers, C. D., Ezzati, M., Jamison, D. T., & Murray, C. J. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68770-9 · Cited by 5,630 · see citing works
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206 · see citing works
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · see citing works
Debacq-Chainiaux, F., Erusalimsky, J. D., Campisi, J., & Toussaint, O. (2009) · Nature Protocols · doi:10.1038/nprot.2009.191 · Cited by 1,668 · see citing works
Cundell, D. R., Gerard, N. P., Gerard, C. J., Idänpään‐Heikkilä, I., & TUOMANEN, E. I. (1995) · Nature · doi:10.1038/377435a0 · Cited by 741 · see citing works
Lexau, C. (2005) · JAMA · doi:10.1001/jama.294.16.2043 · Cited by 671 · see citing works
Bacterial Adhesins in Host-Microbe Interactions
Kline, K. A., Fälker, S., Dahlberg, S., Normark, S. J., & Henriques‐Normark, B. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.05.011 · Cited by 635 · see citing works
Chronic Obstructive Pulmonary Disease (COPD)
Senior, R. M., & Anthonisen, N. R. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.4.nhlbi-12 · Cited by 341 · see citing works
Swords, W. E., Buscher, B. A., Steeg, K. V., Preston, A., Nichols, W. A., Weiser, J. N., Gibson, B. W., & Apicella, M. A. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01952.x · Cited by 310 · see citing works
Orihuela, C. J., Mahdavi, J., Thornton, J., Mann, B., Wooldridge, K. G., Abouseada, N., Oldfield, N. J., Self, T., Ala’Aldeen, D. A. A., & Tuomanen, E. I. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36759 · Cited by 303 · see citing works
Self-citationCoppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · cited 2× · see citing works
“Likewise, they were consistent with the reported SASP profile for senescent HeLa cells (Coppe et al. 2008), and that observed herein for senescent lung epithelial cells.”
ResultCancer and aging: a model for the cancer promoting effects of the aging stroma
Krtolica, A., & Campisi, J. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00053-5 · Cited by 295 · see citing works
O'Brien, L. M., Walsh, E. J., Massey, R. C., Peacock, S. J., & Foster, T. J. (2002) · Cellular Microbiology · doi:10.1046/j.1462-5822.2002.00231.x · Cited by 229 · see citing works
Bleomycin induces cellular senescence in alveolar epithelial cells
Aoshiba, K., Tsuji, T., & Nagai, A. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00011903 · Cited by 197 · see citing works
Modulation of Cell Proliferation by Cytokeratins K10 and K16
Paramio, J. M., Casanova, M., Segrelles, C., Mittnacht, S., Lane, E. B., & Jorcano, J. L. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.3086 · Cited by 181 · see citing works
Neutrophils and low-grade inflammation in the seemingly normal aging human lung
Meyer, K. C., Rosenthal, N. S., Soergel, P., & Peterson, K. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00065-7 · Cited by 179 · see citing works
Obert, C. A., Sublett, J. E., Kaushal, D., Hinojosa, E., Barton, T., TUOMANEN, E. I., & Orihuela, C. J. (2006) · Infection and Immunity · doi:10.1128/iai.00316-06 · Cited by 176 · see citing works
Self-citationImmune dysregulation in the aging human lung
Meyer, K. C., Ershler, W., Rosenthal, N. S., Lu, X. G., & Peterson, K. (1996) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.153.3.8630547 · Cited by 173 · see citing works
Preinfection Systemic Inflammatory Markers and Risk of Hospitalization Due to Pneumonia
Yende, S. P., TUOMANEN, E. I., Wunderink, R. G., Kanaya, A. M., Newman, A. B., Harris, T. B., de Rekeneire, N., & Kritchevsky, S. B. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200506-888oc · Cited by 156 · see citing works
Human diseases of telomerase dysfunction: insights into tissue aging
Garcia, C. K., Wright, W. E., & Shay, J. W. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm644 · Cited by 156 · see citing works
Age‐associated increase in heterochromatic marks in murine and primate tissues
Kreiling, J. A., Tamamori‐Adachi, M., Sexton, A. N., Jeyapalan, J. C., Munoz‐Najar, U., Peterson, A. L., Manivannan, J., Rogers, E. S., Pchelintsev, N. A., Adams, P. D., et al. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2010.00666.x · Cited by 152 · see citing works
Hinojosa, E., Boyd, A. R., & Orihuela, C. J. (2009) · The Journal of Infectious Diseases · doi:10.1086/600870 · Cited by 143 · see citing works
Self-citationThe Streptococcus pneumoniae adhesin PsrP binds to Keratin 10 on lung cells
Shivshankar, P., Sánchez, C. J., Rose, L. F., & Orihuela, C. J. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06796.x · Cited by 138 · see citing works
Self-citationSenescence Hypothesis for the Pathogenetic Mechanism of Chronic Obstructive Pulmonary Disease
Aoshiba, K., & Nagai, A. (2009) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200904-017rm · Cited by 130 · see citing works
Tsuji, T., Aoshiba, K., & Nagai, A. (2009) · Respiration · doi:10.1159/000268287 · Cited by 128 · see citing works
Inhibition of Protein Kinase B (PKB) and PKCζ Mediates Keratin K10-Induced Cell Cycle Arrest
Paramio, J. M., Segrelles, C., Ruiz, S., & Jorcano, J. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.21.7449-7459.2001 · Cited by 122 · see citing works
Avadhanula, V., Rodriguez, C. A., Ulett, G. C., Bakaletz, L. O., & Adderson, E. E. (2006) · Infection and Immunity · doi:10.1128/iai.74.2.830-838.2006 · Cited by 96 · see citing works
Rose, L. F., Shivshankar, P., Hinojosa, E., Rodriguez, A., Sánchez, C. J., & Orihuela, C. J. (2008) · The Journal of Infectious Diseases · doi:10.1086/589775 · Cited by 92 · see citing works
Self-citationThe Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled‐coil
Conners, R., Hill, D. J., Borodina, E. V., Agnew, C., Daniell, S. J., Burton, N. M., Sessions, R. B., Clarke, A. R., Catto, L. E., Lammie, D., et al. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.101 · Cited by 83 · see citing works
Barbier, M., Oliver, A., Rao, J., Hanna, S. L., Goldberg, J. B., & Albertí, S. (2008) · The Journal of Infectious Diseases · doi:10.1086/525048 · Cited by 60 · see citing works
Paterson, G. K., & Orihuela, C. J. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07190.x · Cited by 42 · see citing works
Self-citationWeiner, M. L., Freeman, C., Trochimowicz, H. J., de Gerlache, J., Jacobi, S., Malinverno, G., Mayr, W., & Régnier, J.-F. (2000) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(00)00048-x · Cited by 25 · see citing works
Bacterial Interactions with Mucosal Epithelial Cells
Hurwitz, J. L., Orihuela, C. J., DiRita, V. J., & TUOMANEN, E. I. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-415847-4.00049-5 · Cited by 6 · see citing works
Self-citationChronic obstructive pulmonary disease (COPD)
Nagase, T. (2008) · Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics · doi:10.3143/geriatrics.45.479 · Cited by 5 · see citing works
Bacterial Interactions with Mucosal Epithelial Cells
Orihuela, C. J., Fogg, G. C., DiRita, V. J., & TUOMANEN, E. I. (2005) · Elsevier eBooks · doi:10.1016/b978-012491543-5/50044-9 · Cited by 3 · see citing works
Self-citation
Flagged first, then by citations
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The aging lung: Physiology, disease, and immunity
Schneider, J. L., Rowe, J. H., Garcia-de-Alba, C., Kim, C. F., Sharpe, A. H., & Haigis, M. C. (2021) · Cell · doi:10.1016/j.cell.2021.03.005 · Cited by 500 · see citing works
Cho, S. J., & Stout-Delgado, H. W. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021119-034610 · Cited by 458 · see citing works
Macrophages in age-related chronic inflammatory diseases
Oishi, Y., & Manabe, I. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2016.18 · Cited by 262 · see citing works
Senescent cells: SASPected drivers of age-related pathologies
Ovadya, Y., & Krizhanovsky, V. (2014) · Biogerontology · doi:10.1007/s10522-014-9529-9 · Cited by 232 · see citing works
Mitochondria, telomeres and cell senescence: Implications for lung ageing and disease
Birch, J., Barnes, P. J., & Passos, J. F. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.10.005 · Cited by 173 · see citing works
Innate immune responses in the ageing lung.
Boe, D. M., Boule, L. A., & Kovacs, E. J. (2016) · Clinical and Experimental Immunology · doi:10.1111/cei.12881 · Cited by 156 · see citing works
Sepsis in Old Age: Review of Human and Animal Studies
Starr, M. E. (2014) · Aging and Disease · doi:10.14336/ad.2014.0500126 · Cited by 154 · see citing works
Paradoxical changes in innate immunity in aging: recent progress and new directions
Montgomery, R. R., & Shaw, A. C. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.5mr0315-104r · Cited by 147 · see citing works
Failure of Respiratory Defenses in the Pathogenesis of Bacterial Pneumonia of Cattle
Caswell, J. (2013) · Veterinary Pathology · doi:10.1177/0300985813502821 · Cited by 140 · see citing works
Immunosenescence and pneumococcal disease: an imbalance in host-pathogen interactions.
Krone, C. L., van de Groep, K., Trzciński, K., Sanders, E. A. M., & Bogaert, D. (2014) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(13)70165-6 · Cited by 134 · see citing works
The Impact of Immune System Aging on Infectious Diseases
Quiros-Roldan, E., Sottini, A., Natali, P. G., & Imberti, L. (2024) · Microorganisms · doi:10.3390/microorganisms12040775 · Cited by 133 · see citing works
“…phagocytic killing of neutrophils [191] changes in CD27+IgM+ B cells [194] increase in senescence markers (IL-1 α / β , TNF-α , IL-6, and CXCL1) [192] Escherichia coli and other bacteria inducing urinary tract infections high levels of pro-inflammatory cytokines (IL-6, IL-1 β , and TNF-α )…”
SIRT1 as a therapeutic target in inflammaging of the pulmonary disease
Rahman, I., Kinnula, V. L., Gorbunova, V. A., & Yao, H. (2011) · Preventive Medicine · doi:10.1016/j.ypmed.2011.11.014 · Cited by 120 · see citing works
Cellular senescence in the lung across the age spectrum
Parikh, P., Wicher, S., Khandalavala, K., Pabelick, C. M., Britt, R. D., & Prakash, Y. S. (2019) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00424.2018 · Cited by 112 · see citing works
Goldberg, E. L., Romero-Aleshire, M. J., Renkema, K. R., Ventevogel, M. S., Chew, W. M., Uhrlaub, J. L., Smithey, M. J., Limesand, K. H., Sempowski, G. D., Brooks, H. L., et al. (2014) · Aging Cell · doi:10.1111/acel.12280 · Cited by 102 · see citing works
The Implication of Oxidative Stress and AMPK-Nrf2 Antioxidative Signaling in Pneumonia Pathogenesis
Xu, W., Zhao, T., & Xiao, H. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00400 · Cited by 101 · see citing works
Shivshankar, P., Brampton, C. N., Miyasato, S. K., Kasper, M. E., Thannickal, V. J., & Saux, C. J. L. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2011-0349oc · Cited by 94 · see citing works
Self-citationA role for glycosylated serine‐rich repeat proteins in Gram‐positive bacterial pathogenesis
Lizcano, A., Sanchez, C. J., & Orihuela, C. J. (2012) · Molecular Oral Microbiology · doi:10.1111/j.2041-1014.2012.00653.x · Cited by 92 · see citing works
Self-citationShort, K. R., Reading, P. C., Wang, N., Diavatopoulos, D. A., & Wijburg, O. L. C. (2012) · mBio · doi:10.1128/mbio.00255-12 · Cited by 90 · see citing works
Ghanem, E. N. B., Clark, S. A., Du, X., Wu, D., Camilli, A., Leong, J. M., & Meydani, S. N. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1402401 · Cited by 88 · see citing works
Linton, P., & Thoman, M. L. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.017 · Cited by 86 · see citing works
Bowdish, D. M. E. (2018) · CHEST Journal · doi:10.1016/j.chest.2018.09.003 · Cited by 85 · see citing works
Saux, C. J. L., Davy, P. M. C., Brampton, C. N., Ahuja, S. S., Fauce, S. R., Shivshankar, P., Nguyen, H., Ramaseshan, M., Tressler, R., Pirot, Z., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058423 · Cited by 81 · see citing works
Self-citationSevere COVID-19 Lung Infection in Older People and Periodontitis
Aquino-Martínez, R., & Vigueras, S. H. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10020279 · Cited by 76 · see citing works
Yanagi, S., Tsubouchi, H., Miura, A., Matsuo, A., Matsumoto, N., & Nakazato, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030503 · Cited by 69 · see citing works
Dysregulated inflammation as a risk factor for pneumonia in the elderly.
Boyd, A. R., & Orihuela, C. J. (2011) · Europe PMC (PubMed Central) · Cited by 66 · see citing works
Self-citationInfluenza-Induced Inflammation Drives Pneumococcal Otitis Media
Short, K. R., Reading, P. C., Brown, L. E., Pedersen, J., Gilbertson, B. P., Job, E. R., Edenborough, K. M., Habets, M. N., Zomer, A., Hermans, P. W. M., et al. (2013) · Infection and Immunity · doi:10.1128/iai.01278-12 · Cited by 65 · see citing works
Krone, C. L., Trzciński, K., Zborowski, T., Sanders, E. A. M., & Bogaert, D. (2013) · Infection and Immunity · doi:10.1128/iai.00618-13 · Cited by 63 · see citing works
Hinojosa, C. A., Mgbemena, V. E., Roekel, S. V., Austad, S. N., Miller, R. A., Bose, S., & Orihuela, C. J. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.013 · Cited by 61 · see citing works
Self-citationAdvances in Rodent Experimental Models of Sepsis
Cai, L., Rodgers, E. G., Schoenmann, N., & Raju, R. P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119578 · Cited by 61 · see citing works
Donor Age and Early Graft Failure After Lung Transplantation: A Cohort Study
Baldwin, M. R., Peterson, E. R., Easthausen, I. J., Quintanilla, I., Colago, E., Sonett, J. R., D’Ovidio, F., Costa, J. A., Diamond, J. M., Christie, J. D., et al. (2013) · American Journal of Transplantation · doi:10.1111/ajt.12428 · Cited by 59 · see citing works
Ghanem, E. N. B., Lee, J. N., Joma, B. H., Meydani, S. N., Leong, J. M., & Panda, A. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00161 · Cited by 54 · see citing works
Older but Not Wiser: the Age-Driven Changes in Neutrophil Responses during Pulmonary Infections
Simmons, S. R., Bhalla, M., Herring, S. E., Tchalla, E. Y. I., & Ghanem, E. N. B. (2021) · Infection and Immunity · doi:10.1128/iai.00653-20 · Cited by 54 · see citing works
Current concepts in host–microbe interaction leading to pneumococcal pneumonia
Vernatter, J., & Pirofski, L. (2013) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e3283608419 · Cited by 52 · see citing works
Kovacs, E. J., Boe, D. M., Boule, L. A., & Curtis, B. J. (2017) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2017.06.002 · Cited by 49 · see citing works
Pneumococcal Surface Proteins as Virulence Factors, Immunogens, and Conserved Vaccine Targets
Aceil, J., & Avci, F. Y. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.832254 · Cited by 49 · see citing works
Elevated A20 contributes to age-dependent macrophage dysfunction in the lungs
Hinojosa, C. A., Babu, R. A. S., Rahman, M. M., Fernandes, G., Boyd, A. R., & Orihuela, C. J. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.007 · Cited by 49 · see citing works
Self-citationRespiratory Infections in the Aging Lung: Implications for Diagnosis, Therapy, and Prevention
Häder, A., Köse-Vogel, N., Schulz, L., Mlynska, L., Hornung, F., Hagel, S., Teichgräber, U. K.-M., Lang, S. M., Pletz, M. W., Saux, C. J. L., et al. (2023) · Aging and Disease · doi:10.14336/ad.2023.0329 · Cited by 51 · see citing works
Iovino, F., Brouwer, M. C., van de Beek, D., Molema, G., & Bijlsma, J. J. E. (2013) · Cellular Microbiology · doi:10.1111/cmi.12129 · Cited by 45 · see citing works
How Inflammation Blunts Innate Immunity in Aging
Goldberg, E. L., Shaw, A. C., & Montgomery, R. R. (2020) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000504480 · Cited by 45 · see citing works
The aging lung: microenvironment, mechanisms, and diseases
Wang, Y., Huang, X., Luo, G., Xu, Y., Deng, X., Lin, Y., Wang, Z., Zhou, S., Wang, S., Chen, H., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1383503 · Cited by 46 · see citing works
Senescence and Host–Pathogen Interactions
Humphreys, D., ElGhazaly, M., & Frisan, T. (2020) · Cells · doi:10.3390/cells9071747 · Cited by 40 · see citing works
Elsayed, R., Elashiry, M., Liu, Y., Morandini, A. C., El-Awady, A., Elashiry, M. M., Hamrick, M., & Cutler, C. W. (2023) · Aging and disease · doi:10.14336/ad.2022.0623 · Cited by 40 · see citing works
Novick, S., Shagan, M., Blau, K., Lifshitz, S., Givon‐Lavi, N., Grossman, N., Bodner, L., Dagan, R., & Nebenzahl, Y. M. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.5996 · Cited by 40 · see citing works
Animal Models of Pneumococcal pneumonia
Borsa, N., Pasquale, M. F. D., & Restrepo, M. I. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174220 · Cited by 36 · see citing works
Contribution of viral and bacterial infections to senescence and immunosenescence
Reyes, A., Ortiz, G., Duarte, L. F., Fernández, C., Hernández‐Armengol, R., Palacios, P. A., Prado, Y., Andrade, C. A., Rodríguez‐Guilarte, L., Kalergis, A. M., et al. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1229098 · Cited by 36 · see citing works
Association between Maturation and Aging and Pulmonary Responses in Animal Models of Lung Injury
Schouten, L. R. A., Schultz, M. J., van Kaam, A. H., Juffermans, N. P., Bos, A. P., & Asperen, R. M. W. (2015) · Anesthesiology · doi:10.1097/aln.0000000000000687 · Cited by 34 · see citing works
Immune ageing and susceptibility to Streptococcus pneumoniae
Gonçalves, M. T., Mitchell, T. J., & Lord, J. M. (2015) · Biogerontology · doi:10.1007/s10522-015-9614-8 · Cited by 33 · see citing works
Co‐ and polymicrobial infections in the gut mucosa: The host–microbiota–pathogen perspective
Frisan, T. (2020) · Cellular Microbiology · doi:10.1111/cmi.13279 · Cited by 33 · see citing works
Faniyi, A. A., Hughes, M., Scott, A., Belchamber, K. B. R., & Sapey, E. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15759 · Cited by 32 · see citing works
Biofilm and planktonic pneumococci demonstrate disparate immunoreactivity to human convalescent sera
Sánchez, C. J., Hurtgen, B. J., Lizcano, A., Shivshankar, P., Cole, G. T., & Orihuela, C. J. (2011) · BMC Microbiology · doi:10.1186/1471-2180-11-245 · Cited by 31 · see citing works
Self-citationImmune aging and infectious diseases
Chen, R., Zou, J., Chen, J., Wang, L., Kang, R., & Tang, D. (2024) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003410 · Cited by 33 · see citing works
Shukla, S. D., Sohal, S. S., O’Toole, R., Eapen, M. S., & Walters, E. H. (2015) · Expert Review of Respiratory Medicine · doi:10.1586/17476348.2015.1070673 · Cited by 29 · see citing works
Haas, K. M., Blevins, M. W., High, K. P., Pang, B., Swords, W. E., & Yammani, R. D. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit442 · Cited by 29 · see citing works
Grigg, J. (2012) · Thorax · doi:10.1136/thoraxjnl-2012-202206 · Cited by 28 · see citing works
P. aeruginosa interactions with other microbes in biofilms during co-infection
Oliveira, M., Cunha, E. S., Tavares, L. M., & Serrano, I. D. (2023) · AIMS Microbiology · doi:10.3934/microbiol.2023032 · Cited by 27 · see citing works
Bhalla, M., Yeoh, J. H., Lamneck, C., Herring, S. E., Tchalla, E. Y. I., Heinzinger, L. R., Leong, J. M., & Ghanem, E. N. B. (2019) · Cellular Microbiology · doi:10.1111/cmi.13141 · Cited by 26 · see citing works
Kamio, N., Hayata, M., Tamura, M., Tanaka, H., & Imai, K. (2021) · FEBS Letters · doi:10.1002/1873-3468.14084 · Cited by 26 · see citing works
Blanchette, K. A., & Orihuela, C. J. (2012) · Future Microbiology · doi:10.2217/fmb.11.160 · Cited by 25 · see citing works
Self-citationConvergence in the Epidemiology and Pathogenesis of COPD and Pneumonia
Gautam, S., & O’Toole, R. (2016) · COPD Journal of Chronic Obstructive Pulmonary Disease · doi:10.1080/15412555.2016.1191456 · Cited by 25 · see citing works
Cellular senescence in normal and premature lung aging
Bartling, B. (2013) · Zeitschrift für Gerontologie und Geriatrie · doi:10.1007/s00391-013-0543-3 · Cited by 24 · see citing works
Beyond the Hayflick limit: How microbes influence cellular aging
Abavisani, M., Faraji, S., Ebadpour, N., Karav, S., & Sahebkar, A. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102657 · Cited by 24 · see citing works
Role of caveolin-1 in asthma and chronic inflammatory respiratory diseases
Royce, S. G., & Saux, C. J. L. (2014) · Expert Review of Respiratory Medicine · doi:10.1586/17476348.2014.905915 · Cited by 23 · see citing works
Grant, L. R., Slack, M., Yan, Q., Trzciński, K., Barratt, J., Sobczyk, E. A., Appleby, J. C., Cane, A. D., Jódar, L., Istúriz, R., et al. (2021) · Expert Review of Vaccines · doi:10.1080/14760584.2021.1921579 · Cited by 22 · see citing works
Torrelles, J. B., Restrepo, B. I., Bai, Y., Ross, C. N., Schlesinger, L. S., & Turner, J. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.818700 · Cited by 23 · see citing works
Guo, G., Watterson, S., Zhang, S., Bjourson, A. J., McGilligan, V., Peace, A. J., & Singh, T. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101363 · Cited by 20 · see citing works
Drechsler, S., Lynch, M. A., Novella, S., Navarro, H. G., Hecimovic, S. K., Barini, E., Tucci, V., Castro, R. E., Vandenbroucke, R. E., Osuchowski, M. F., et al. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.07.005 · Cited by 18 · see citing works
The Stress of Lung Aging: Endoplasmic Reticulum and Senescence Tête-à-Tête
Ngassie, M. L. K., Brandsma, C., Gosens, R., Prakash, Y. S., & Burgess, J. K. (2021) · Physiology · doi:10.1152/physiol.00039.2020 · Cited by 18 · see citing works
Association Between Periodontal Disease and the Risk of COVID-19 Complications and Mortality
Espinoza, D. A. K. E., Dulanto-Vargas, J. A., Torre, A. C. L., Lamas-Castillo, F. E., Flores‐Mir, C., Cervantes‐Ganoza, L., López‐Gurreonero, C., Castañeda, M. I. L., & Cayo-Rojas, C. F. (2021) · Journal of International Society of Preventive and Community Dentistry · doi:10.4103/jispcd.jispcd_189_21 · Cited by 18 · see citing works
Pinto, K. G., Nascimento, D. O., Corrêa-Ferreira, A., Morrot, A., Freire-de-Lima, C. G., Lopes, M. F., DosReis, G. A., & Filardy, A. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01569 · Cited by 17 · see citing works
Gonzales, J., Chakraborty, T., Romero, M. J., Mraheil, M. A., Kutlar, A., Pace, B. S., & Lucas, R. (2021) · Toxins · doi:10.3390/toxins13020157 · Cited by 16 · see citing works
Lizcano, A., Babu, R. A. S., Shenoy, A. T., Saville, A. M., Kumar, N., D’Mello, A., Hinojosa, C. A., Gilley, R. P., Segovia, J. A., Mitchell, T. J., et al. (2017) · Microbes and Infection · doi:10.1016/j.micinf.2017.04.001 · Cited by 16 · see citing works
Self-citationShaikh, S. B., Goracci, C., Tjitropranoto, A., & Rahman, I. (2023) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2023.2205127 · Cited by 14 · see citing works
Urban, B. C., Gonçalves, A. N. A., Loukov, D., Passos, F. M., Reiné, J., Gonzalez‐Dias, P., Solórzano, C., Mitsi, E., Nikolaou, E., O’Connor, D., et al. (2024) · Mucosal Immunology · doi:10.1016/j.mucimm.2024.06.010 · Cited by 14 · see citing works
Janesch, P., Stulik, L., Rouha, H., Varga, C., Steinhäuser, J., Zerbs, M., & Nagy, E. (2018) · Cytokine · doi:10.1016/j.cyto.2018.09.012 · Cited by 14 · see citing works
Oral and systemic health: is there a “new” link with COVID-19?
Herrera, D., Serrano, J., Roldán, S., Alonso, B., & Sanz, M. (2023) · Clinical Oral Investigations · doi:10.1007/s00784-023-04950-2 · Cited by 13 · see citing works
Kruckow, K. L., Murray, E., Shayhidin, E., Rosenberg, A. F., Bowdish, D. M. E., & Orihuela, C. J. (2024) · Aging Cell · doi:10.1111/acel.14133 · Cited by 11 · see citing works
Self-citationWeight, C. M., Jochems, S. P., Adler, H., Ferreira, D. M., Brown, J., & Heyderman, R. S. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.651474 · Cited by 11 · see citing works
Melchio, R., Giamello, J. D., Testa, E., Iturriaga, L. A. R., Falcetta, A., Serraino, C., Riva, P., Bracco, C., Fernández, L. S., D’Agnano, S., et al. (2021) · Internal and Emergency Medicine · doi:10.1007/s11739-020-02615-6 · Cited by 8 · see citing works
KRT5+/p63+ Stem Cells Undergo Senescence in the Human Lung with Pathological Aging
Moreno‐Valladares, M., Moncho-Amor, V., Silva, T. M., Garcés, J. P., Álvarez‐Satta, M., & Matheu, A. (2023) · Aging and Disease · doi:10.14336/ad.2022.1128 · Cited by 8 · see citing works
Can animal models really teach us anything about pneumonia? Pro
Orihuela, C. J., Maus, U. A., & Brown, J. (2020) · European Respiratory Journal · doi:10.1183/13993003.01539-2019 · Cited by 8 · see citing works
Self-citationMechanisms of Predisposition to Pneumonia
Infante, A. J., McCullers, J. A., & Orihuela, C. J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-410530-0.00019-3 · Cited by 8 · see citing works
Self-citationRolewska, P., Simm, A., Silber, R., & Bartling, B. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0057oc · Cited by 8 · see citing works
Fernandes, S. E., Alakesh, A., Rajmani, R. S., Jhunjhunwala, S., & Saini, D. K. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119063 · Cited by 7 · see citing works
Lu, R., Huang, Q. M., Yu, T., Liu, D., & Hong, X. (2025) · BMC Cardiovascular Disorders · doi:10.1186/s12872-025-04702-y · Cited by 6 · see citing works
Jirru, E., Lee, S. F., Harris, R. M., Yang, J., Cho, S. J., & Stout-Delgado, H. W. (2020) · Vaccines · doi:10.3390/vaccines8020298 · Cited by 6 · see citing works
Understanding the impact of ER stress on lung physiology
Fu, Z., Wang, W., & Gao, Y. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1466997 · Cited by 6 · see citing works
Acute effects of ambient air pollution exposure on lung function in the elderly in Hangzhou, China
Liao, H., Chen, S., Xu, S., Lv, Y., Liu, W., & Xu, H. (2022) · International Journal of Environmental Health Research · doi:10.1080/09603123.2022.2067523 · Cited by 8 · see citing works
Pneumococcal Pili and Adhesins
Hilleringmann, M., Köhler, S., Gámez, G., & Hammerschmidt, S. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-410530-0.00017-x · Cited by 6 · see citing works
Bacterial Interactions with Mucosal Epithelial Cells
Hurwitz, J. L., Orihuela, C. J., DiRita, V. J., & TUOMANEN, E. I. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-415847-4.00049-5 · Cited by 6 · see citing works
Self-citationJaramillo‐Rangel, G., Chávez-Briones, M.-D.-L., Ancer-Arellano, A., Miranda-Maldonado, I. C., & Ortega‐Martínez, M. (2023) · Biomedicines · doi:10.3390/biomedicines11072075 · Cited by 5 · see citing works
Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk
Lee, M.-M., Zuo, Y., Steiling, K. A., Mizgerd, J. P., Kalesan, B., & Walkey, A. J. (2024) · PLoS ONE · doi:10.1371/journal.pone.0296139 · Cited by 5 · see citing works
Immunity, Inflammation, and Aging
Meyer, K. C. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-397803-5.00003-4 · Cited by 5 · see citing works
Effect of physical activity in lymphocytes senescence burden in patients with COPD
Alfaro, E., Díaz‐García, E., García-Tovar, S., Galera, R., Casitas, R., Martínez-Cerón, E., Torres-Vargas, M., Padilla, J. M., López-Fernández, C., Pérez-Moreno, P., et al. (2024) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00151.2024 · Cited by 4 · see citing works
Korpak, K., Rossi, M., MEERHAEGHE, A. V., Boudjeltia, K. Z., & Compagnie, M. (2024) · Nutrition and Healthy Aging · doi:10.3233/nha-220184 · Cited by 3 · see citing works
Age-Associated Changes in Structure and Function of the Aging Human Lung
Meyer, K. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00064-6 · Cited by 3 · see citing works
Age-Related Dysfunction in the Innate Immune Response to Lung Infections
Boe, D. M., Chen, M. M., & Kovacs, E. J. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_91 · Cited by 3 · see citing works
Wnt signaling pathway in lung aging and aging-related chronic lung diseases
Wu, J., Dean, W. D., Hejing, W., & Jing, L. (2025) · Biogerontology · doi:10.1007/s10522-025-10367-z · Cited by 2 · see citing works
Shivshankar, P. (2012) · ISRN Inflammation · doi:10.5402/2012/267101 · Cited by 2 · see citing works
Self-citationAging and respiratory infections in laboratory animals
Манских, В. Н. (2015) · Advances in Gerontology · doi:10.1134/s2079057015010075 · Cited by 2 · see citing works
From systemic disease to the eye: Why senescence deserves attention in ocular infections
Maiti, S., & Joseph, J. (2026) · Experimental Eye Research · doi:10.1016/j.exer.2026.111095 · Cited by 1 · see citing works
- Authors
- Shivshankar, P., Boyd, A. R., Le Saux, C. J., Yeh, I., & Orihuela, C. J.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Orihuela, Carlos J.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2011-06-14
- Volume
- 10
- Issue
- 5
- Pages
- 798-806
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3173515
- OpenAlex
- W1569854985
- Cited by
- 117
- References
- 37
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 9 · 2022: 4 · 2021: 14 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 15 · 2012: 7
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG092313, R21AG029313, AG033274, R21AG033274)
- National Institute of Allergy and Infectious Diseases (R01AI078972, AI078972)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, pneumococcal pneumonia, Streptococcus pneumoniae, bacterial adhesion, keratin 10, laminin receptor, platelet-activating factor receptor, senescence-associated secretory phenotype, lung inflammation, p16, oxidative stress, genotoxic stress, aged mice, bacterial ligands
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Aging, Animals, Bacterial Adhesion, Bleomycin, Disease Susceptibility, Female, Humans, Immunohistochemistry, Inflammation, Lung, Mice, Inbred BALB C, Middle Aged, Pneumonia, Pneumococcal, Streptococcus pneumoniae, Immunoblotting, Biomarkers, Cytokines, Cellular Senescence, Receptors, Laminin, Oxidative Stress, Cell Line, Tumor, Mice, Kaplan-Meier Estimate, Keratin-10
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