Immunosenescence: a product of the environment?
Open accessAbstract
The major function of the immune system is to provide protection against pathogens, in order to prevent infections and potential death. However, with increasing age the immune system undergoes alterations culminating in a progressive deterioration in the ability to respond to infection and vaccination. The precise mechanisms associated with immunosenescence have not been fully elucidated although extensive analyses have suggested that intrinsic defects within immune cells are potentially involved. Despite the stromal niche playing a critical role in the development and activation of immune cells, the role of extrinsic factors within the microenvironment in immunosenescence is less well understood. Moreover, emerging evidence suggests that the aged microenvironment contributes significantly to the age-associated decline of immune function and additionally may offer a potential target for rejuvenating the immune system. Indeed, rejuvenation strategies which have targeted the thymic stromal microenvironment have proved to be successful in recovering thymic function in the aged.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
The tumor microenvironment may accelerate senescence of the immune system.
“However, the main obstacle to achieving efficacious immunotherapy is the tumor microenvironment (TME), which may accelerate senescence of the immune system [18, 19]: potential targets for rejuvenating the immune system are still a hypothesis.”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [19]
Cites
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · see citing works
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,180 · see citing works
Immunosenescence: emerging challenges for an ageing population
Aw, D., Silva, A. B., & Palmer, D. B. (2007) · Immunology · doi:10.1111/j.1365-2567.2007.02555.x · Cited by 880 · see citing works
Self-citationmTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
Yilmaz, Ö. H., Katajisto, P., Lamming, D. W., Gültekin, Y., Bauer-Rowe, K. E., Sengupta, S., Birsoy, K., Dursun, A., Yilmaz, V. O., Selig, M., et al. (2012) · Nature · doi:10.1038/nature11163 · Cited by 753 · see citing works
mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells
Chen, C., Liu, Y., Liu, Y., & Zheng, P. (2009) · Science Signaling · doi:10.1126/scisignal.2000559 · Cited by 680 · see citing works
New member of the winged-helix protein family disrupted in mouse and rat nude mutations
Nehls, M. C., Pfeifer, D., Schorpp, M., Hedrich, H. J., & Boehm, T. L. J. (1994) · Nature · doi:10.1038/372103a0 · Cited by 635 · see citing works
Distinct Hematopoietic Stem Cell Subtypes Are Differentially Regulated by TGF-β1
Challen, G. A., Boles, N. C., Chambers, S. M., & Goodell, M. A. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.02.002 · Cited by 580 · see citing works
Thymic involution and immune reconstitution.
Lynch, H. E., Goldberg, G. L., Chidgey, A., Van den Brink, M. R. M., Boyd, R., & Sempowski, G. D. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.04.003 · Cited by 522 · see citing works
Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?
Akbar, A. N., & Henson, S. M. (2011) · Nature Reviews Immunology · doi:10.1038/nri2959 · Cited by 474 · see citing works
Lymphostromal interactions in thymic development and function
Anderson, G., & Jenkinson, E. J. (2001) · Nature reviews. Immunology · doi:10.1038/35095500 · Cited by 461 · see citing works
Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells
Gray, D. H. D., Seach, N., Ueno, T., Milton, M. K., Liston, A., Lew, A. M., Goodnow, C. C., & Boyd, R. L. (2006) · Blood · doi:10.1182/blood-2006-02-004531 · Cited by 458 · see citing works
Human immunosenescence: is it infectious?
Pawelec, G., Akbar, A., Caruso, C., Solana, R., Grubeck‐Loebenstein, B., & Wikby, A. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00271.x · Cited by 405 · see citing works
Interleukin-22 Drives Endogenous Thymic Regeneration in Mice
Dudakov, J. A., Hanash, A. M., Jenq, R. R., Young, L. F., Ghosh, A., Singer, N. V., West, M. L., Smith, O. M., Holland, A. M., Tsai, J. J.-Y., et al. (2012) · Science · doi:10.1126/science.1218004 · Cited by 392 · see citing works
Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver
Stanger, B. Z., Tanaka, A., & Melton, D. A. (2007) · Nature · doi:10.1038/nature05537 · Cited by 385 · see citing works
An evolutionary perspective on the mechanisms of immunosenescence
Shanley, D. P., Aw, D., Manley, N. R., & Palmer, D. B. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.05.001 · Cited by 315 · see citing works
Changes in primary lymphoid organs with aging
Chinn, I. K., Blackburn, C. C., Manley, N. R., & Sempowski, G. D. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.005 · Cited by 282 · see citing works
Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing
Ergen, A. V., Boles, N. C., & Goodell, M. A. (2012) · Blood · doi:10.1182/blood-2011-11-391730 · Cited by 280 · see citing works
Form follows function: lymphoid tissue microarchitecture in antimicrobial immune defence
Junt, T., Scandella, E., & Ludewig, B. (2008) · Nature reviews. Immunology · doi:10.1038/nri2414 · Cited by 264 · see citing works
Androgen Receptors in Thymic Epithelium Modulate Thymus Size and Thymocyte Development
Olsen, N. J., Olson, G. E., Viselli, S. M., Gu, X., & Kovacs, W. J. (2001) · Endocrinology · doi:10.1210/endo.142.3.8032 · Cited by 244 · see citing works
McElhaney, J. E., Zhou, X., Talbot, H. K., Soethout, E., Bleackley, R. C., Granville, D. J., & Pawelec, G. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.01.015 · Cited by 229 · see citing works
Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner
Chen, L., Xiao, S., & Manley, N. R. (2008) · Blood · doi:10.1182/blood-2008-05-156265 · Cited by 221 · see citing works
Min, D., Panoskaltsis-Mortari, A., Kuro-o, M., Holländer, G. A., Blazar, B. R., & Weinberg, K. I. (2007) · Blood · doi:10.1182/blood-2006-08-043794 · Cited by 214 · see citing works
Stem cells and the aging hematopoietic system
Beerman, I., Maloney, W. J., Weissman, I. L., & Rossi, D. J. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.06.007 · Cited by 206 · see citing works
Ghrelin promotes thymopoiesis during aging
Dixit, V. D., Yang, H., Sun, Y., Weeraratna, A. T., Youm, Y., Smith, R. G., & Taub, D. D. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30248 · Cited by 204 · see citing works
Ortman, C. (2002) · International Immunology · doi:10.1093/intimm/dxf042 · Cited by 195 · see citing works
The Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence
Youm, Y.-H., Kanneganti, T.-D., Vandanmagsar, B., Zhu, X., Ravussin, A., Adijiang, A., Owen, J. S., Thomas, M. J., Francis, J., Parks, J. S., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2011.11.005 · Cited by 172 · see citing works
Zook, E. C., Krishack, P. A., Zhang, S., Zeleznik‐Le, N. J., Firulli, A. B., Witte, P. L., & Le, P. T. (2011) · Blood · doi:10.1182/blood-2011-03-342097 · Cited by 148 · see citing works
ΔNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2
Candi, E., Rufini, A., Terrinoni, A., Miraglia, A. G., Lena, A. M., Mantovani, R., Knight, R. A., & Melino, G. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703458104 · Cited by 147 · see citing works
Barbieri, C. E., & Pietenpol, J. A. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.11.028 · Cited by 140 · see citing works
Griffith, A. V., Fallahi, M., Venables, T., & Petrie, H. T. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00773.x · Cited by 120 · see citing works
Postnatal Tissue-specific Disruption of Transcription Factor FoxN1 Triggers Acute Thymic Atrophy
Cheng, L., Guo, J., Sun, L., Fu, J., Barnes, P. F., METZGER, D., Chambon, P., Oshima, R. G., Amagai, T., & Su, D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.072124 · Cited by 115 · see citing works
Self-citationIntrathymic IL-7: The where, when, and why of IL-7 signaling during T cell development
Hong, C.-W., Luckey, M. A., & Park, J.-H. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.02.002 · Cited by 111 · see citing works
CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1
Murooka, T. T., Rahbar, R., Platanias, L. C., & Fish, E. N. (2008) · Blood · doi:10.1182/blood-2007-11-125039 · Cited by 109 · see citing works
The aged microenvironment contributes to the age‐related functional defects of CD4 T cells in mice
Lefebvre, J. S., Maue, A. C., Eaton, S. M., Lanthier, P. A., Tighe, M. P., & Haynes, L. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00836.x · Cited by 105 · see citing works
Lymphohematopoietic progenitors do not have a synchronized defect with age‐related thymic involution
Zhu, X., Gui, J., Dohkan, J., Cheng, L., Barnes, P. F., & Su, D. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00325.x · Cited by 103 · see citing works
Self-citationAlterations in Marginal Zone Macrophages and Marginal Zone B Cells in Old Mice
Birjandi, S. Z., Ippolito, J. A., Ramadorai, A. K., & Witte, P. L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001271 · Cited by 92 · see citing works
Sun, L., Guo, J., Brown, R., Amagai, T., Zhao, Y., & Su, D. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00559.x · Cited by 83 · see citing works
Self-citationAging of the microenvironment influences clonality in hematopoiesis
Vas, V., Senger, K., Dörr, K., Niebel, A., & Geiger, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042080 · Cited by 83 · see citing works
Aspinall, R., Pido-Lopez, J., Imami, N., Henson, S. M., N’Gom, P. T., Morre, M., Niphuis, H., Remarque, E. J., Rosenwirth, B., & Heeney, J. L. (2007) · Rejuvenation Research · doi:10.1089/rej.2006.9098 · Cited by 82 · see citing works
Cbx4 regulates the proliferation of thymic epithelial cells and thymus function
Liu, B., Liu, Y.-F., Du, Y., Mardaryev, A. N., Yang, W., Chen, H., Xu, Z.-M., Xu, C., Zhang, X., Botchkarev, V. A., et al. (2013) · Development · doi:10.1242/dev.085035 · Cited by 78 · see citing works
Kilpinen, L., Tigistu‐Sahle, F., Oja, S., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m030650 · Cited by 72 · see citing works
An Epithelial Progenitor Pool Regulates Thymus Growth
Jenkinson, W. E., Bacon, A., White, A. J., Anderson, G., & Jenkinson, E. J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.6101 · Cited by 70 · see citing works
Garfin, P. M., Min, D., Bryson, J. L., Serwold, T. F., Edris, B., Blackburn, C. C., Richie, E. R., Weinberg, K. I., Manley, N. R., Sage, J., et al. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20121716 · Cited by 69 · see citing works
The origin and implication of thymic involution.
Aw, D., & Palmer, D. B. (2011) · Europe PMC (PubMed Central) · Cited by 67 · see citing works
Self-citationConcise Review: Hematopoietic Stem Cell Aging, Life Span, and Transplantation
Zant, G. E. V., & Liang, Y. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0033 · Cited by 61 · see citing works
Aging of hematopoietic stem cells: Intrinsic changes or micro-environmental effects?
Woolthuis, C. M., de Haan, G., & Huls, G. A. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.05.006 · Cited by 59 · see citing works
Contribution of an Aged Microenvironment to Aging-Associated Myeloproliferative Disease
Vas, V., Wandhoff, C., Dörr, K., Niebel, A., & Geiger, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031523 · Cited by 55 · see citing works
Reversal of age-associated thymic atrophy: Treatments, delivery, and side effects
Aspinall, R., & Mitchell, W. A. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.04.014 · Cited by 44 · see citing works
Migration of immature and mature B cells in the aged microenvironment
Wols, H. A. M., Johnson, K. M., Ippolito, J. A., Birjandi, S. Z., Su, Y. A., Le, P. T., & Witte, P. L. (2009) · Immunology · doi:10.1111/j.1365-2567.2009.03182.x · Cited by 42 · see citing works
The stem cell niche: tissue physiology at a single cell level
Hoggatt, J., & Scadden, D. T. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60238 · Cited by 40 · see citing works
Sun, L., Brown, R. E., Chen, S., Zhuge, Q., & Su, D. (2012) · Aging · doi:10.18632/aging.100487 · Cited by 33 · see citing works
Self-citationJoiner, D. M., Tayim, R. J., Kadado, A. A., & Goldstein, S. A. (2012) · Biogerontology · doi:10.1007/s10522-012-9391-6 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
The Effect of Age on Thymic Function
Palmer, D. B. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00316 · Cited by 494 · see citing works
Self-citationContributions 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 · see citing works
Self-citationSuccessful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362 · see citing works
Immunosenescence and vaccine failure in the elderly: strategies for improving response
Boraschi, D., & Italiani, P. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.006 · Cited by 86 · see citing works
Telomere shortening and immune activity in war veterans with posttraumatic stress disorder
Jergović, M., Tomičević, M., Vidović, A., Bendelja, K., Savić, A., Vojvoda, V., Rac, D., Lovrić-Čavar, D., Rabatić, S., Jovanovic, T., et al. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.06.010 · Cited by 67 · see citing works
- Authors
- Su, D.-M., Aw, D., & Palmer, D. B.
- Affiliations
- University of North Texas Health Science Center (US)
- University of London (GB)
- Corresponding author
- Palmer, Donald B
- ORCID
- Su, Dong-Ming
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 25
- Issue
- 4
- Pages
- 498-503
- ISSN
- 0952-7915 (ISSN-L)
- OpenAlex
- W1988422147
- Cited by
- 41
- References
- 52
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 2
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- immunosenescence, aging, immune system decline, thymus, vaccine response, infection susceptibility, external factors
- MeSH terms
- Aging, Animals, Bone Marrow, Cell Differentiation, Hematopoietic Stem Cells, Humans, Immune System, Thymocytes
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
