Cited by 282T-cell and B-cell ImmunologyHematopoietic Stem Cell TransplantationGenetics, Aging, and Longevity in Model Organisms

The DOI matches its Crossref record; 158 of the 158 references it cites were found in a registry or an index.

Changes in primary lymphoid organs with aging

Open access

Chinn, Ivan K., Blackburn, Clare C., Manley, Nancy R., Sempowski, Gregory D.·2012·Seminars in Immunology

DOI 10.1016/j.smim.2012.04.005PMC PMC3415579

Open this paper in CoChat — free account

Abstract

Aging is associated with decreased immune function that leads to increased morbidity and mortality in the elderly. Immune senescence is accompanied by age-related changes in two primary lymphoid organs, bone marrow and thymus, that result in decreased production and function of B and T lymphocytes. In bone marrow, hematopoietic stem cells exhibit reduced self-renewal potential, increased skewing toward myelopoiesis, and decreased production of lymphocytes with aging. These functional sequelae of aging are caused in part by increased oxidative stress, inflammation, adipocyte differentiation, and disruption of hypoxic osteoblastic niches. In thymus, aging is associated with tissue involution, exhibited by a disorganization of the thymic epithelial cell architecture and increased adiposity. This dysregulation correlates with a loss of stroma-thymocyte 'cross-talk', resulting in decreased export of naïve T cells. Mounting evidence argues that with aging, thymic inflammation, systemic stress, local Foxn1 and keratinocyte growth factor expression, and sex steroid levels play critical roles in actively driving thymic involution and overall adaptive immune senescence across the lifespan. With a better understanding of the complex mechanisms and pathways that mediate bone marrow and thymus involution with aging, potential increases for the development of safe and effective interventions to prevent or restore loss of immune function with aging.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.smim.2012.04.005

Cites

158 of 158 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
Osteoblastic cells regulate the haematopoietic stem cell niche
Calvi, L. M., Adams, G. B., Weibrecht, K. W., Weber, J. M., Olson, D. P., Knight, M. C., Martin, R. P., Schipani, E., Pajevic, P. D., Bringhurst, F. R., et al. (2003) · Nature · doi:10.1038/nature02040 · Cited by 3,559
Identification of the haematopoietic stem cell niche and control of the niche size
Zhang, J., Niu, C. S., Ye, L., Huang, H., He, X. C., Tong, W.-G., Ross, J., Haug, J., Johnson, T. J., Feng, J. Q., et al. (2003) · Nature · doi:10.1038/nature02041 · Cited by 2,948
Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2007) · JAMA · doi:10.1001/jama.297.8.842 · Cited by 2,275
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., McDowell, E. P., Lazo-Kallanian, S., Williams, I. R., Sears, C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.003 · Cited by 1,562
Mice Lacking p27 Display Increased Body Size, Multiple Organ Hyperplasia, Retinal Dysplasia, and Pituitary Tumors
Nakayama, K., Ishida, N., Shirane, M., Inomata, A., Inoue, T., SHISHIDO, N., Horii, I., Loh, D. Y., & Nakayama, K. (1996) · Cell · doi:10.1016/s0092-8674(00)81237-4 · Cited by 1,548
A Syndrome of Multiorgan Hyperplasia with Features of Gigantism, Tumorigenesis, and Female Sterility in p27 -Deficient Mice
Fero, M. L., Rivkin, M. J., Tasch, M., Porter, P. L., Carow, C. E., Firpo, E. J., Polyák, K., Tsai, L., Broudy, V. C., Perlmutter, R. M., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81239-8 · Cited by 1,459
Enhanced Growth of Mice Lacking the Cyclin-Dependent Kinase Inhibitor Function of p27
Kiyokawa, H., Kineman, R. D., Manova-Todorova, K. O., Soares, V., Hoffman, E. S., Ono, M., Khanam, D., Hayday, A., Frohman, L. A., & Koff, A. (1996) · Cell · doi:10.1016/s0092-8674(00)81238-6 · Cited by 1,243
Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., et al. (2004) · Nature · doi:10.1038/nature02989 · Cited by 1,175 · cited 2×
“Treatment with N-acetylcysteine or catalase decreased intracellular ROS levels in HSCs and restored hematopoietic reconstitutive capacity of the cells [28], thus emphasizing the additional impact of ROS on HSC functional decline with aging.”
Background
Unified nomenclature for the winged helix/forkhead transcription factorsPreprint
Kaestner, K. H., Knöchel, W., & Martínez, D. E. (2000) · Genes & Development · doi:10.1101/gad.14.2.142 · Cited by 1,162

Flagged first, then by citations

Show all 158 references

Research works printed but not linked: 1

Wagegg, 2010, Adipogenic and osteogenic switch in differentiation of human mesenchymal stem cells (hMSCs) is triggered by hypoxia in a HIF-1 dependent manner [abstract], Arthritis Rheumatism, 62, 630

Sorted by citations

The twilight of immunity: emerging concepts in aging of the immune system
Nikolich-Žugich, J. (2018) · Nature Immunology · doi:10.1038/s41590-017-0006-x · Cited by 1,240
Understanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827
Causes, consequences, and reversal of immune system aging
Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64096 · Cited by 793
SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes
Nikolich-Zugich, J., Knox, K. S., Rios, C. T., Natt, B., Bhattacharya, D., & Fain, M. J. (2020) · GeroScience · doi:10.1007/s11357-020-00186-0 · Cited by 577
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510
Senescent cell clearance by the immune system: Emerging therapeutic opportunities
Prata, L. G. P. L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2019.04.003 · Cited by 497
The Effect of Age on Thymic Function
Palmer, D. B. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00316 · Cited by 494
Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging
Thomas, R., Wang, W., & Su, D.-M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-0173-8 · Cited by 442
Successful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362
Naive T Cell Maintenance and Function in Human Aging
Goronzy, J. J., Fang, F., Cavanagh, M., Qi, Q., & Weyand, C. M. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500046 · Cited by 362
Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians
Hashimoto, K., Kouno, T., Ikawa, T., Hayatsu, N., Miyajima, Y., Yabukami, H., Terooatea, T., Sasaki, T., Suzuki, T., Valentine, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907883116 · Cited by 343
Emerging Concepts and Technologies in Vaccine Development
Brisse, M. E., Vrba, S. M., Kirk, N. M., Liang, Y., & Ly, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.583077 · Cited by 329
Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood
Duggal, N. A., Pollock, R. D., Lazarus, N. R., Harridge, S., & Lord, J. M. (2018) · Aging Cell · doi:10.1111/acel.12750 · Cited by 261
Aging of the T Cell Compartment in Mice and Humans: From No Naive Expectations to Foggy Memories
Nikolich-Žugich, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401174 · Cited by 259
IBD across the age spectrum—is it the same disease?
Ruel, J., Ruane, D., Mehandru, S., Gower‐Rousseau, C., & Colombel, J. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.240 · Cited by 244
Thymus and aging: morphological, radiological, and functional overview
Rezzani, R., Nardo, L., Favero, G., Peroni, M., & Rodella, L. F. (2013) · AGE · doi:10.1007/s11357-013-9564-5 · Cited by 198
Regeneration of the aged thymus by a single transcription factor
Bredenkamp, N., Nowell, C. S., & Blackburn, C. C. (2014) · Development · doi:10.1242/dev.103614 · Cited by 194
Self-citation
Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses
Pulko, V., Davies, J. S., Martinez, C., Lanteri, M. C., Busch, M. P., Diamond, M. S., Knox, K., Bush, E. C., Sims, P. A., Sinari, S., et al. (2016) · Nature Immunology · doi:10.1038/ni.3483 · Cited by 175
The Biology of Recent Thymic Emigrants
Fink, P. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-100010 · Cited by 186
An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts
Bredenkamp, N., Ulyanchenko, S., O’Neill, K. E., Manley, N. R., Vaidya, H. J., & Blackburn, C. C. (2014) · Nature Cell Biology · doi:10.1038/ncb3023 · Cited by 172
Self-citation
Long-term maintenance of human naive T cells through in situ homeostasis in lymphoid tissue sites
Thome, J. J. C., Grinshpun, B., Kumar, B. V., Kubota, M., Ohmura, Y., Lerner, H., Sempowski, G. D., Shen, Y., & Farber, D. L. (2016) · Science Immunology · doi:10.1126/sciimmunol.aah6506 · Cited by 162
Self-citation
Activation of immunosuppressive network in the aging process
Salminen, A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100998 · Cited by 155
Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs
Steegenga, W. T., Boekschoten, M. V., Lute, C., Hooiveld, G. J. E. J., de Groot, P. J., Morris, T. J., Teschendorff, A. E., Butcher, L. M., Beck, S., & Müller, M. M. (2014) · AGE · doi:10.1007/s11357-014-9648-x · Cited by 150
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration
Wertheimer, T., Velardi, E., Tsai, J. J.-Y., Cooper, K., Xiao, S., Kloss, C. C., Jarick, K. J., Mokhtari, Z., Brede, C., DeRoos, P. C., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aal2736 · Cited by 132
Self-citation
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
“…these modifications are linked to the immune system response to permanent stress. self-renewal potential and increased skewing toward myelopoiesis [28], probably because of compromised Pax5 expression and Rag2 recombinase function and bone marrow niche alterations This novel vision considers…”
Myeloid-Derived Suppressor Cells: Not Only in Tumor Immunity
Pawelec, G., Verschoor, C. P., & Ostrand‐Rosenberg, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01099 · Cited by 126
From causes of aging to death from COVID-19
Blagosklonny, M. V. (2020) · Aging · doi:10.18632/aging.103493 · Cited by 128
The Changing Landscape of Naive T Cell Receptor Repertoire With Human Aging
Egorov, E. S., Kasatskaya, S. A., Zubov, V. N., Izraelson, M., Nakonechnaya, T. O., Staroverov, D. B., Angius, A., Cucca, F., Mamedov, I. Z., Rosati, E., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01618 · Cited by 117
Type 2 cytokine signaling in macrophages protects from cellular senescence and organismal aging
Zhou, Z., Yao, J., Wu, D., Huang, X., Wang, Y., Li, X., Lu, Q., & Qiu, Y. (2024) · Immunity · doi:10.1016/j.immuni.2024.01.001 · Cited by 122
Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus
Ulyanchenko, S., O’Neill, K. E., Medley, T. L., Farley, A., Vaidya, H. J., Cook, A., Blair, N. F., & Blackburn, C. C. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.02.080 · Cited by 117
Self-citation
Global Transcriptional Profiling Reveals Distinct Functions of Thymic Stromal Subsets and Age-Related Changes during Thymic Involution
Ki, S., Park, D., Selden, H. J., Seita, J., Chung, H., Kim, J., Iyer, V. R., & Ehrlich, L. I. R. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.070 · Cited by 116
Lifespan‐extending caloric restriction or m TOR inhibition impair adaptive immunity of old mice by distinct mechanisms
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 107
Self-citation
The role of myeloid-derived suppressor cells (MDSC) in the inflammaging process
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.09.001 · Cited by 101
Thymic rejuvenation and aging
Ventevogel, M. S., & Sempowski, G. D. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.06.002 · Cited by 90
Self-citation
Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease
Bueno, V., Sant’Anna, O. A., & Lord, J. M. (2014) · AGE · doi:10.1007/s11357-014-9729-x · Cited by 95
Inhibition of B Lymphopoiesis by Adipocytes and IL-1–Producing Myeloid-Derived Suppressor Cells
Kennedy, D. E., & Knight, K. L. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500957 · Cited by 97
ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01904-z · Cited by 99
Age-related susceptibility to coronavirus infections: role of impaired and dysregulated host immunity
Channappanavar, R., & Perlman, S. M. (2020) · Journal of Clinical Investigation · doi:10.1172/jci144115 · Cited by 94
Functional and Homeostatic Impact of Age-Related Changes in Lymph Node Stroma
Thompson, H. L., Smithey, M. J., Surh, C. D., & Nikolich‐Žugich, J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00706 · Cited by 87
Multiscale engineering of immune cells and lymphoid organs
Kim, S., Shah, S. B., Graney, P. L., & Singh, A. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0100-9 · Cited by 79
Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution
Barbouti, A., Vasileiou, P. V. S., Evangelou, K., Vlasis, K. G., Papoudou‐Bai, A., Gorgoulis, V. G., & Kanavaros, P. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/7986071 · Cited by 86
Regulatory pathways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocorticoid therapy and radiotherapy.
Georgiou, K. R., Hui, S. K., & Xian, C. J. (2012) · Europe PMC (PubMed Central) · Cited by 80
Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
Zhang, L., Mack, R. M., Breslin, P., & Zhang, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00994-z · Cited by 80
Reactive oxygen species contribute to dysfunction of bone marrow hematopoietic stem cells in aged C57BL/6 J mice
Porto, M. L., Rodrigues, B. P., Menezes, T. N., Ceschim, S. L., Casarini, D. E., Gava, A. L., Pereira, T. D. M. C., Vasquez, E. C., Campagnaro, B. P., & Meyrelles, S. S. (2015) · Journal of Biomedical Science · doi:10.1186/s12929-015-0201-8 · Cited by 82
Lymph nodes as barriers to T‐cell rejuvenation in aging mice and nonhuman primates
Thompson, H. L., Smithey, M. J., Uhrlaub, J. L., Jeftic, I. D., Jergović, M., White, S. E., Currier, N., Lang, A. M., Okoye, A. A., Park, B. S., et al. (2018) · Aging Cell · doi:10.1111/acel.12865 · Cited by 75
Targeting cellular senescence in metabolic disease
Palmer, A. K., Tchkonia, T., & Kirkland, J. L. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101601 · Cited by 76
Age-Related Changes in Thymic Central Tolerance
Srinivasan, J., Lancaster, J. N., Singarapu, N., Hale, L. P., Ehrlich, L. I. R., & Richie, E. R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.676236 · Cited by 67
Aging of the hematopoietic system
Snoeck, H. (2013) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3283623c77 · Cited by 73
A 2020 View of Thymus Stromal Cells in T Cell Development
Han, J., & Zúñiga‐Pflücker, J. C. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2000889 · Cited by 64
Immunosenescence, Aging, and Systemic Lupus Erythematous
Montoya-Ortiz, G. (2013) · Autoimmune Diseases · doi:10.1155/2013/267078 · Cited by 70
Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis
Shirafkan, F., Hensel, L., & Rattay, K. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1339714 · Cited by 67
Immune senescence: significance of the stromal microenvironment
Masters, A. R., Haynes, L., Su, D.-M., & Palmer, D. B. (2016) · Clinical & Experimental Immunology · doi:10.1111/cei.12851 · Cited by 65
Restoration of Thymus Function with Bioengineered Thymus Organoids
Tajima, A., Pradhan, I., Trucco, M., & Fan, Y. (2016) · Current Stem Cell Reports · doi:10.1007/s40778-016-0040-x · Cited by 65
Administration of RANKL boosts thymic regeneration upon bone marrow transplantation
Lopes, N., Vachon, H., Marie, J. C., & Irla, M. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201607176 · Cited by 61
Does senescence affect lymph node number and morphology? A systematic review
Ahmadi, O., McCall, J. L., & Stringer, M. D. (2013) · ANZ Journal of Surgery · doi:10.1111/ans.12067 · Cited by 57
Thymus aging and immune reconstitution, progresses and challenges
Li, Y. R., & Zúñiga‐Pflücker, J. C. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101837 · Cited by 57
Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution
Hamazaki, Y., Sekai, M., & Minato, N. (2016) · Immunological Reviews · doi:10.1111/imr.12412 · Cited by 55
The Dual Role of the Pervasive “Fattish” Tissue Remodeling With Age
Conte, M., Martucci, M., Sandri, M., Franceschi, C., & Salvioli, S. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00114 · Cited by 58
Physiologic Thymic Involution Underlies Age-Dependent Accumulation of Senescence-Associated CD4+ T Cells
Sato, K., Kato, A., Sekai, M., Hamazaki, Y., & Minato, N. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1602005 · Cited by 54
Overexpression of wild-type IL-7Rα promotes T-cell acute lymphoblastic leukemia/lymphoma
Silva, A., Almeida, A. R. M., Cachucho, A., Neto, J. L., Demeyer, S., Matos, M., Hogan, T. V., Li, Y., Meijerink, J. P. P., Cools, J., et al. (2021) · Blood · doi:10.1182/blood.2019000553 · Cited by 54
Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19
Lega, S., Naviglio, S., Volpi, S., & Tommasini, A. (2020) · Vaccines · doi:10.3390/vaccines8020224 · Cited by 56
Tissue-Specific Gene Expression Changes are Associated with Aging in Mice
Srivastava, A., Barth, E., Ermolaeva, M., Guenther, M., Frahm, C., Marz, M., & Witte, O. W. (2020) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2020.12.001 · Cited by 54
Regulation of the Immune System Development by Glucocorticoids and Sex Hormones
Quatrini, L., Ricci, B., Ciancaglini, C., Tumino, N., & Moretta, L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.672853 · Cited by 51
Thymic stromal cells: Roles in atrophy and age-associated dysfunction of the thymus
Cepeda, S., & Griffith, A. V. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.12.022 · Cited by 53
Non-Epithelial Thymic Stromal Cells: Unsung Heroes in Thymus Organogenesis and T Cell Development
Nitta, T., & Takayanagi, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.620894 · Cited by 48
Blocking the FSTL1-DIP2A Axis Improves Anti-tumor Immunity
Kudo‐Saito, C., Ishida, A., Shouya, Y., Teramoto, K., Igarashi, T., Kon, R., Saito, K., Awada, C., Ogiwara, Y., & Toyoura, M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.043 · Cited by 47
In situ evidence of cellular senescence in Thymic Epithelial Cells (TECs) during human thymic involution
Barbouti, A., Evangelou, K., Pateras, I. S., Papoudou-Bai, A., Patereli, A., Stefanaki, K., Rontogianni, D., Muñoz-Espín, D., Kanavaros, P., & Gorgoulis, V. G. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.02.005 · Cited by 44
Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease
Hasib, L., Lundberg, A. K., Zachrisson, H., Ernerudh, J., & Jonasson, L. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12398 · Cited by 44
Effect of IL-7 Therapy on Naive and Memory T Cell Homeostasis in Aged Rhesus Macaques
Okoye, A. A., Rohankhedkar, M., Konfe, A. L., Abana, C. O., Reyes, M. D., Clock, J. A., Duell, D. M., Sylwester, A. W., Sammader, P., Legasse, A. W., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500609 · Cited by 44
Dynamic regulation of Notch1 activation and Notch ligand expression in human thymus development
García-León, M. J., Fuentes, P., de la Pompa, J. L., & Toribio, M. L. (2018) · Development · doi:10.1242/dev.165597 · Cited by 44
Health disparities: Intracellular consequences of social determinants of health
Emeny, R. T., Carpenter, D. O., & Lawrence, D. A. (2021) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2021.115444 · Cited by 47
Zinc deficiency as possible link between immunosenescence and age-related diseases
Schulz, M. T., & Rink, L. (2025) · Immunity & Ageing · doi:10.1186/s12979-025-00511-1 · Cited by 50
Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis
Kennedy, D. E., & Knight, K. L. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601643 · Cited by 44
Immunosenescence: a product of the environment?
Su, D.-M., Aw, D., & Palmer, D. B. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.05.018 · Cited by 41
Age-Associated Changes to Lymph Node Fibroblastic Reticular Cells
Kwok, T., Medovich, S. C., Silva, I., Brown, E. M., Haug, J. C., Barrios, M. R., Morris, K. A., & Lancaster, J. N. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.838943 · Cited by 42
Metallothionein and stress combine to affect multiple organ systems
Lynes, M. A., Hidalgo, J., Manso, Y., Devisscher, L., Laukens, D., & Lawrence, D. A. (2014) · Cell Stress and Chaperones · doi:10.1007/s12192-014-0501-z · Cited by 41
The Inherent Human Aging Process and the Facilitating Role of Exercise
Lazarus, N. R., & Harridge, S. D. R. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01135 · Cited by 43
The fibroblast: An emerging key player in thymic T cell selection
Nitta, T., Ota, A., Iguchi, T., Muro, R., & Takayanagi, H. (2021) · Immunological Reviews · doi:10.1111/imr.12985 · Cited by 41
Exosome-mediated delivery of superoxide dismutase for anti-aging studies in Caenorhabditis elegans
Shao, X., Zhang, M., Chen, Y., Sun, S., Yang, S., & Li, Q. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123090 · Cited by 39
Single-cell RNA sequencing unveils the hidden powers of zebrafish kidney for generating both hematopoiesis and adaptive antiviral immunity
Hu, C., Zhang, N., Hong, Y. M., Tie, R., Fan, D., Lin, A., Chen, Y., Xiang, L., & Shao, J.-Z. (2024) · eLife · doi:10.7554/elife.92424 · Cited by 39
Adult thymic epithelial cell (TEC) progenitors and TEC stem cells: Models and mechanisms for TEC development and maintenance
Hamazaki, Y. (2015) · European Journal of Immunology · doi:10.1002/eji.201545844 · Cited by 37
The natural killer cell dysfunction of aged mice is due to the bone marrow stroma and is not restored by IL ‐15/ IL ‐15Rα treatment
Nair, S., Fang, M., & Sigal, L. J. (2014) · Aging Cell · doi:10.1111/acel.12291 · Cited by 38
Late Effects of Exposure to Ionizing Radiation and Age on Human Thymus Morphology and Function
Ito, R., Hale, L. P., Geyer, S. M., Li, J., Sornborger, A. T., Kajimura, J., Kusunoki, Y., Yoshida, K., van den Brink, M. R. M., Kyoizumi, S., et al. (2017) · Radiation Research · doi:10.1667/rr4554.1 · Cited by 37
Self-citation
Sublethal Total Body Irradiation Causes Long-Term Deficits in Thymus Function by Reducing Lymphoid Progenitors
Xiao, S., Shterev, I. D., Zhang, W., Young, L. F., Shieh, J.-H., Moore, M. A. S., van den Brink, M. R. M., Sempowski, G. D., & Manley, N. R. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1600934 · Cited by 39
Self-citation
Review of Influenza Virus Vaccines: The Qualitative Nature of Immune Responses to Infection and Vaccination Is a Critical Consideration
Chan, L., Alizadeh, K., Alizadeh, K., Fazel, F., Kakish, J. E., Karimi, N., Knapp, J. P., Mehrani, Y., Minott, J. A., Morovati, S., et al. (2021) · Vaccines · doi:10.3390/vaccines9090979 · Cited by 40
Enhanced Hematopoietic Stem Cell Function Mediates Immune Regeneration following Sex Steroid Blockade
Khong, D., Dudakov, J. A., Hammett, M. V., Jurblum, M. I., Khong, S. M. L., Goldberg, G. L., Ueno, T., Spyroglou, L., Young, L. F., van den Brink, M. R. M., et al. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.01.018 · Cited by 40
Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells
Satoh, R., Kakugawa, K., Yasuda, T., Yoshida, H., Sibilia, M. C., Katsura, Y., Levi, B. Z., Abramson, J., Koseki, Y., Koseki, H., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005776 · Cited by 36
Role of the Nuclear Lamina in Age-Associated Nuclear Reorganization and Inflammation
Kristiani, L., Kim, M., & Kim, Y. (2020) · Cells · doi:10.3390/cells9030718 · Cited by 36
Self-recognition drives the preferential accumulation of promiscuous CD4(+) T-cells in aged mice
Deshpande, N. R., Parrish, H. L., & Kuhns, M. S. (2015) · eLife · doi:10.7554/elife.05949 · Cited by 35
Immunosenescence and cancer: Opportunities and challenges
Fu, Z., Xu, H., Yue, L., Zheng, W., Pan, L., Gao, F., & Liu, X. (2023) · Medicine · doi:10.1097/md.0000000000036045 · Cited by 37
Compartmentalized effects of aging on group 2 innate lymphoid cell development and function
D’Souza, S. S., Shen, X., Fung, I. T. H., Ye, L., Kuentzel, M. L., Chittur, S. V., Furuya, Y., Siebel, C. W., Maillard, I. P., Metzger, D. W., et al. (2019) · Aging Cell · doi:10.1111/acel.13019 · Cited by 36
Adaptive immunity and atherosclerosis: aging at its crossroads
Snijckers, R., & Foks, A. C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1350471 · Cited by 40
Central tolerance is impaired in the middle‐aged thymic environment
Lancaster, J. N., Keatinge-Clay, D. L., Srinivasan, J., Li, Y., Selden, H. J., Nam, S., Richie, E. R., & Ehrlich, L. I. R. (2022) · Aging Cell · doi:10.1111/acel.13624 · Cited by 33
Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus
Sun, L., Brown, R. E., Chen, S., Zhuge, Q., & Su, D. (2012) · Aging · doi:10.18632/aging.100487 · Cited by 36
Decline of FOXN1 gene expression in human thymus correlates with age: possible epigenetic regulation
Reis, M. D. D. S., Csomós, K., Dias, L. P. B., Prodàn, Z., Szerafin, T., Savino, W., & Takács, L. (2015) · Immunity & Ageing · doi:10.1186/s12979-015-0045-9 · Cited by 34
Intrinsic and extrinsic contributors to defective CD8+ T cell responses with aging
Jergović, M., Smithey, M. J., & Nikolich‐Žugich, J. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.01.011 · Cited by 33
Cell‐type‐specific role of lamin‐B1 in thymus development and its inflammation‐driven reduction in thymus aging
Yue, S., Zheng, X., & Zheng, Y. (2019) · Aging Cell · doi:10.1111/acel.12952 · Cited by 32
Innovative Medicine
Nakao, K., Minato, N., & Üemoto, S. (2015) · Springer eBooks · doi:10.1007/978-4-431-55651-0 · Cited by 34
MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19
Bumiller‐Bini, V., Oliveira, C. F., Carvalho, T. M., Kretzschmar, G. C., Gonçalves, L. B., Alencar, N. M., Filho, M. A. G., Beltrame, M. H., & Boldt, A. B. W. (2021) · Genetics and Molecular Biology · doi:10.1590/1678-4685-gmb-2020-0199 · Cited by 30
CD147 deficiency in T cells prevents thymic involution by inhibiting the EMT process in TECs in the presence of TGFβ
Chen, R., Wang, K., Feng, Z., Zhang, M.-Y., Wu, J., Geng, J., & Chen, Z. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0353-7 · Cited by 31

Authors: Chinn, I. K., Blackburn, C. C., Manley, N. R., & Sempowski, G. D.
Affiliations: Duke Medical Center (US)
MRC Centre for Regenerative Medicine (GB)
University of Georgia (US)
Corresponding author: Sempowski, Gregory D.
ORCID: Chinn, Ivan K.
Blackburn, Clare C.
Manley, Nancy R.
Sempowski, Gregory D.
Venue: Seminars in Immunology
Publisher: Elsevier BV
Published: 2012-10
Volume: 24
Issue: 5
Pages: 309-320
ISSN: 1044-5323 (ISSN-L)
DOI: 10.1016/j.smim.2012.04.005
PMC: PMC3415579
OpenAlex: W2136991900
Cited by: 282
References: 158
Citations by year: 2026: 12 · 2025: 8 · 2024: 17 · 2023: 14 · 2022: 26 · 2021: 23 · 2020: 31 · 2019: 26 · 2018: 25 · 2017: 18 · 2016: 20 · 2015: 22 · 2014: 20 · 2013: 17 · 2012: 3
FWCI: 1.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Seminars in Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Leukaemia and Lymphoma Research
Directorate for Biological Sciences
Biotechnology and Biological Sciences Research Council (BB/H021183/1)
National Institute on Aging (AG035302, AG-025150, R01AG035302, R01AG025150)
National Institute of Allergy and Infectious Diseases (R01AI082127, HHSN272200900059C, R01AI055001, AI076514, AI082127, UC6AI058607, P01AI076514)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD043494, K12HD043494)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: immunosenescence, aging, primary lymphoid organs, thymic involution, hematopoietic stem cells, myelopoiesis, oxidative stress, Foxn1, keratinocyte growth factor, sex steroids, adipose tissue, B cells, T cells
MeSH terms: Aging, Animals, Bone Marrow, Humans, Immunity, Innate, Lymphatic System, Cell Hypoxia, Oxidative Stress

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Changes in primary lymphoid organs with aging

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks