p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells
Open accessAbstract
T cell senescence is thought to contribute to immune function decline, but the pathways that mediate senescence in these cells are not clear. Here, we evaluated T cell populations from healthy volunteers and determined that human CD8+ effector memory T cells that reexpress the naive T cell marker CD45RA have many characteristics of cellular senescence, including decreased proliferation, defective mitochondrial function, and elevated levels of both ROS and p38 MAPK. Despite their apparent senescent state, we determined that these cells secreted high levels of both TNF-α and IFN-γ and showed potent cytotoxic activity. We found that the senescent CD45RA-expressing population engaged anaerobic glycolysis to generate energy for effector functions. Furthermore, inhibition of p38 MAPK signaling in senescent CD8+ T cells increased their proliferation, telomerase activity, mitochondrial biogenesis, and fitness; however, the extra energy required for these processes did not arise from increased glucose uptake or oxidative phosphorylation. Instead, p38 MAPK blockade in these senescent cells induced an increase in autophagy through enhanced interactions between p38 interacting protein (p38IP) and autophagy protein 9 (ATG9) in an mTOR-independent manner. Together, our findings describe fundamental metabolic requirements of senescent primary human CD8+ T cells and demonstrate that p38 MAPK blockade reverses senescence via an mTOR-independent pathway.
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Increased glycolysis and reactive oxygen species (ROS) production are features of immunosenescence.
“T cell–output decline is an important feature of immunosenescence as well as the production of senescence-associated secretory phenotype, increased glycolysis, and reactive oxygen species.”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [36]
Aging T cells preferentially employ anaerobic glycolysis to generate energy, resulting in mitochondrial dysfunction and increased ROS generation.
“Moreover, aging T cells preferentially employ anaerobic glycolysis to generate energy, which results in mitochondrial dysfunction and increased reactive oxygen species (ROS) generation [36].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [36]
Within primary human T cells, both CD4+ and CD8+ populations contain a subset of poorly proliferative cells with characteristics very similar to senescent fibroblasts.
“Within primary human T cells, in both CD4 + [23, 28, 29] and CD8 + [25, 30] populations, there is a subset of poorly proliferative cells that exhibit characteristics that are very similar to senescent fibroblasts (Fig. 1).”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
T cells within both CD4+ and CD8+ compartments that have senescent characteristics increase during ageing.
“An important observation is that T cells within both CD4 + and CD8 + compartments that have senescent characteristics increase during ageing [25, 33-38] and are therefore likely to have an impact on altered immune function in older individuals.”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
The increase in senescent T cells during ageing is likely to have an impact on altered immune function in older individuals.
“An important observation is that T cells within both CD4 + and CD8 + compartments that have senescent characteristics increase during ageing [25, 33-38] and are therefore likely to have an impact on altered immune function in older individuals.”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Highly differentiated CD27-CD28- T cells that re-express CD45RA have multiple characteristics of senescence including loss of telomerase activity, DNA damage, high levels of reactive oxygen species and the lowest proliferative capacity.
“The highly differentiated CD27 - CD28 - population of T cells can be further divided and the cells that re-express CD45RA within this subset have multiple characteristics of senescence including loss of telomerase activity, DNA damage, high levels of reactive oxygen species (ROS) and the lowest proliferative capacity [25, 30].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
CD45RA re-expressing senescent T cells do not have critically short telomeres, suggesting that senescence in these cells may be induced by other mechanisms including DNA damage by increased ROS production.
“Intriguingly, the CD45RA re-expressing senesecent T cells do not have critically short telomeres suggesting that senescence in these cell may be induced by other mechanisms including DNA damage by increased ROS production [25, 30].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
p38 signalling inhibited autophagy in senescent T cells via a non-canonical mTORC1 independent process involving increased trafficking of the autophagy regulating protein Atg9 from the endosomes to the lysosomes.
“It was found that the p38 signalling inhibited autophagy in senescent T cells, a non-canonical mTORC1 independent process, that occurs instead via a mechanism that involved increased trafficking of the autophagy regulating protein Atg9 from the endosomes to the lysosomes [25].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Senescent CD8+ T cells exhibit mitochondrial dysfunction, increased production of reactive oxygen species and impaired mitochondrial biogenesis, which may explain their dependence on glycolysis for energy.
“Senescent CD8 + T cells exhibit mitochondrial dysfunction, increased production of reactive oxygen species (ROS) and impaired mitochondrial biogenesis, which may explain their dependence on glycolysis for energy [25].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Despite increased mitochondrial function, senescent T cells still preferentially utilize glycolysis and not OXPHOS for increased proliferation after p38 blockade.
“However despite the increased mitochondrial function, senescent T cells still preferentially utilize glycolysis and not OXPHOS for increased proliferation after p38 blockade.”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Blocking p38 enhanced autophagy, increased mitochondrial biogenesis, cleared dysfunctional mitochondria and reduced ROS production in senescent CD8+ T cells, indicating an overall improvement of mitochondrial fitness.
“Blocking p38 enhanced autophagy, increased mitochondrial biogenesis, cleared dysfunctional mitochondria and reduced ROS production in senescent CD8 + T cells [25] indicating an overall improvement of mitochondrial fitness.”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Defective autophagy results in a failure to clear the large giant dysfunctional mitochondria that is linked to increased ROS production by senescent CD8+ T cells.
“Nevertheless, the defective autophagy results in a failure to clear the large giant dysfunctional mitochondria that is linked to increased ROS production by senescent CD8 + T cells [25].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Senescent CD8+ T cells display both low autophagic activity and lack mTORC1 activity.
“However senescent CD8 + T cells displayed both low autophagic activity [25, 65] and also lack mTORC1 activity [25].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Based on in vitro data, blocking agents to p38 could be used in vivo to enhance certain T cell functions.
“One target for reversing senescence in T cells would be the p38 MAP kinase pathway and based on data that has been obtained in vitro , blocking agents to p38 could be used in vivo to enhance certain T cell functions [23-25, 30] .”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
The lack of mitochondrial biogenesis in senescent T cells may be a consequence of the failure of these cells to activate mTOR, as demonstrated by their inability to phosphorylate mTORC1 or mTORC2.
“The lack of mitochondrial biogenesis may well be a consequence of the failure of senescent T cells to activate mTOR (mammaliam target of rapamycin), a central integrator of immune signalling and cell metabolism [62], as demonstrated by their inability to phosphorylate the mTOCR1 [25] or the mTORC2 complex [63].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Recycling of metabolic precursors resulting from increased autophagy, and not greater glucose uptake, fuels the enhanced proliferative activity of senescent T cells after p38 inhibition.
“Furthermore, the recycling of metabolic precursors resulting from increased autophagy and not greater glucose uptake fuels the enhanced proliferative activity of senescent T cells after p38 inhibition.”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
Human senescent CD8+ T cells preferentially utilise glycolysis to generate ATP, as opposed to the effector memory subset which is more metabolically flexible and can use either glycolysis or oxidative phosphorylation.
“It was shown that human senescent CD8 + T cells preferentially utilise glycolysis to generate ATP, as opposed to the effector memory subset which are much more metabolically flexible and can either glycolysis or oxidative phosphorylation (OXPHOS) for functional activities (Fig. 3).”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
There is an interrelationship between senescence, nutrition and inflammation in regulating T cell function.
“the new awareness of the interrelationship between senescence, nutrition and inflammation in regulating T cell function [25, 29, 61].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [25]
The p38-MAPK pathway plays a pleiotropic role in cell survival, both sustaining proliferation and inducing apoptosis in a cell type-specific manner, depending on the type of stimulus.
“The p38-MAPK pathway plays a pleiotropic role in cell survival, both sustaining proliferation, and inducing apoptosis in a cell type-specific manner, depending on the type of stimulus (185).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [185]
Autophagy, by inhibiting cell senescence, is a critical regulator of memory CD8+ formation, and age-related autophagy defect is one explanation why CD8+ T memory formation becomes defective in old age.
“Autophagy, by inhibiting cell senescence, is a critical regulator of memory CD8+ formation, and age-related autophagy defect is one of the explanations why CD8+ T memory formation becomes defective in old age (38, 185).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [185]
In senescent CD8+ T cells, p38-MAPK induces an increase in autophagy through interactions between a p38 interacting protein and autophagy protein 9, in an mTOR-independent manner, suggesting that p38-MAPK blockade reverses senescence via an mTOR-independent pathway.
“Moreover, in senescent CD8+ T cells, p38-MAPK induces an increase in autophagy through interactions between a p38 interacting protein and autophagy protein 9, in a mTOR-independent manner, suggesting that p38-MAPK blockade reverses senescence via mTOR-independent pathway (185).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [185]
High levels of reactive oxygen species in T cells impair cytotoxicity, perhaps mediated by T cell lipid peroxidation, resulting in failure to control viruses.
“and high levels of reactive oxygen species in T cells impair cytotoxicity, perhaps mediated by T cell lipid peroxidation, resulting in failure to control viruses (Henson et al. 2014; Matsushita et al. 2015).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Henson et al. 2014
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Cites
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227 · see citing works
Mammalian MAP kinase signalling cascades
Chang, L., & Karin, M. (2001) · Nature · doi:10.1038/35065000 · Cited by 5,118 · 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
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057 · see citing works
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,855 · see citing works
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103 · see citing works
mTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575 · see citing works
Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development
van der Windt, G. J. W., Everts, B., Chang, C.-H., Curtis, J. D., Freitas, T. C., Amiel, E., Pearce, E. J., & Pearce, E. L. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.007 · Cited by 1,540 · see citing works
Reversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457 · see citing works
Metabolic Regulation of T Lymphocytes
MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095956 · Cited by 1,244 · see citing works
Brenchley, J. M., Karandikar, N. J., Betts, M. R., Ambrozak, D. R., Hill, B. J., Crotty, L. E., Casazza, J. P., Kuruppu, J., Migueles, S. A., Connors, M., et al. (2003) · Blood · doi:10.1182/blood-2002-07-2103 · Cited by 1,073 · see citing works
Freund, A., Patil, C. K., & Campisi, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.69 · Cited by 1,039 · see citing works
Regulation of Immune Responses by mTOR
Powell, J. D., Pollizzi, K. N., Heikamp, E. B., & Horton, M. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075024 · Cited by 836 · see citing works
SPICE: Exploration and analysis of post‐cytometric complex multivariate datasets
Roederer, M., Nozzi, J. L., & Nason, M. (2011) · Cytometry Part A · doi:10.1002/cyto.a.21015 · Cited by 833 · see citing works
Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes
Young, A. R. J., Chan, E. Y. W., Hu, X. W., Köchl, R., Crawshaw, S. G., High, S., Hailey, D. W., Lippincott-Schwartz, J., & Tooze, S. A. (2006) · Journal of Cell Science · doi:10.1242/jcs.03172 · Cited by 815 · see citing works
Self-citationPhenotype and function of human T lymphocyte subsets: Consensus and issues
Appay, V., van Lier, R. A. W., Sallusto, F., & Roederer, M. (2008) · Cytometry Part A · doi:10.1002/cyto.a.20643 · Cited by 729 · see citing works
Canonical and non-canonical autophagy: variations on a common theme of self-eating?
Codogno, P., Mehrpour, M., & Proikas‐Cezanne, T. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3249 · Cited by 545 · see citing works
The metabolic footprint of aging in mice
Houtkooper, R. H., Argmann, C., Houten, S. M., Cantó, C., Jeninga, E. H., Andreux, P. A., Thomas, C., Doenlen, R., Schoonjans, K., & Auwerx, J. (2011) · Scientific Reports · doi:10.1038/srep00134 · Cited by 528 · see citing works
New insights into the role of mitochondria in aging: mitochondrial dynamics and more
Seo, A. Y., Joseph, A.-M., Dutta, D., Hwang, J. C. Y., Aris, J. P., & Leeuwenburgh, C. (2010) · Journal of Cell Science · doi:10.1242/jcs.070490 · Cited by 522 · see citing works
Integration of cellular bioenergetics with mitochondrial quality control and autophagy
Hill, B. G., Benavides, G. A., Lancaster, J. R., Ballinger, S. W., Dell’Italia, L., Zhang, J., & Darley-Usmar, V. M. (2012) · Biological Chemistry · doi:10.1515/hsz-2012-0198 · Cited by 481 · 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
Self-citationAutophagy facilitates glycolysis during Ras-mediated oncogenic transformation
Lock, R., Roy, S., Kenific, C. M., Su, J. S., Salas, E., Ronen, S. M., & Debnath, J. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-06-0500 · Cited by 467 · see citing works
MAPKAP kinases — MKs — two's company, three's a crowd
Gaestel, M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1834 · Cited by 413 · see citing works
Four functionally distinct populations of human effector-memory CD8+ T lymphocytes
Romero, P., Zippelius, A., Kurth, I., Pittet, M. J., Touvrey, C., Iancu, E. M., Corthesy, P., Devevre, E., Speiser, D. E., & Rufer, N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4112 · Cited by 405 · see citing works
Mitogen‐activated protein kinase p38 defines the common senescence‐signalling pathway
Iwasa, H., Han, J., & Ishikawa, F. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00620.x · Cited by 388 · see citing works
Mortensen, M., Ferguson, D. J. P., Edelmann, M. J., Kessler, B. M., Morten, K., Komatsu, M., & Simon, A. K. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913170107 · Cited by 388 · see citing works
Self-citationMultiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people
Koch, S. D., Larbi, A., Derhovanessian, E., Özcelik, D., Naumova, E. J., & Pawelec, G. (2008) · Immunity & Ageing · doi:10.1186/1742-4933-5-6 · Cited by 360 · see citing works
Glucose Availability Regulates IFN-γ Production and p70S6 Kinase Activation in CD8+ Effector T Cells
Cham, C. M., & Gajewski, T. F. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4670 · Cited by 359 · see citing works
Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway
Yamamoto, A., Cremona, M. L., & Rothman, J. E. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200510065 · Cited by 355 · see citing works
Voehringer, D., Koschella, M., & Pircher, H. (2002) · Blood · doi:10.1182/blood-2002-02-0657 · Cited by 352 · see citing works
Hodes, R. J., Hathcock, K. S., & Weng, N. (2002) · Nature reviews. Immunology · doi:10.1038/nri890 · Cited by 315 · see citing works
Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine kinases
Salvador, J. M., Mittelstadt, P. R., Guszczynski, T., Copeland, T. D., Yamaguchi, H., Appella, E., Fornace, A. J., & Ashwell, J. D. (2005) · Nature Immunology · doi:10.1038/ni1177 · Cited by 306 · see citing works
Coppé, 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
“Another defining feature of fibroblast senescence is the acquisition of a senescence-associated secretory phenotype (SASP), featuring the secretion of growth factors, proteases, and inflammatory cytokines that affect neighboring cells in a paracrine manner (3).”
Human CD8+ T-cell differentiation in response to viruses
van Lier, R. A. W., ten Berge, I. J. M., & Gamadia, L. E. (2003) · Nature Reviews Immunology · doi:10.1038/nri1254 · Cited by 297 · see citing works
Yang, K., Neale, G. A. M., Green, D. R., He, W., & Chi, H. (2011) · Nature Immunology · doi:10.1038/ni.2068 · Cited by 294 · see citing works
Itakura, E., Kishi-Itakura, C., Koyama-Honda, I., & Mizushima, N. (2012) · Journal of Cell Science · doi:10.1242/jcs.094110 · Cited by 286 · see citing works
Henson, S. M., Franzese, O., Macaulay, R., Libri, V., Azevedo, R. I., Kiani-Alikhan, S., Plunkett, F. J., Masters, J. E., Jackson, S., Griffiths, S. J., et al. (2009) · Blood · doi:10.1182/blood-2009-01-199588 · Cited by 262 · see citing works
Self-citationCoordinated regulation of autophagy by p38α MAPK through mAtg9 and p38IP
Webber, J. L., & Tooze, S. A. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.321 · Cited by 251 · see citing works
Self-citationLiu, K., Hodes, R. J., & Weng, N. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.8.4826 · Cited by 234 · see citing works
Reversible Senescence in Human CD4+CD45RA+CD27− Memory T Cells
Di Mitri, D., Azevedo, R. I., Henson, S. M., Libri, V., Riddell, N. E., Macaulay, R., Kipling, D., Soares, M. V. D., Battistini, L., & Akbar, A. N. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100978 · Cited by 231 · see citing works
Self-citationPlunkett, F. J., Franzese, O., Finney, H. M., Fletcher, J. M., Belaramani, L. L., Salmon, M., Dokal, I., Webster, D., Lawson, A. D. G., & Akbar, A. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.12.7710 · Cited by 222 · see citing works
Self-citationMetabolism, migration and memory in cytotoxic T cells
Finlay, D. K., & Cantrell, D. A. (2011) · Nature reviews. Immunology · doi:10.1038/nri2888 · Cited by 220 · see citing works
Faint, J. M., Annels, N. E., Curnow, S. J., Shields, P., Pilling, D., Hislop, A. D., Wu, L., Akbar, A. N., Buckley, C. D., Moss, P. A. H., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.1.212 · Cited by 171 · see citing works
Self-citationChu, C. T., Zhu, J.-H., & Dagda, R. (2007) · Autophagy · doi:10.4161/auto.4625 · Cited by 170 · see citing works
Song, Z., Von Figura, G., Liu, Y., Kraus, J. M., Torrice, C., Dillon, P., Rudolph‐Watabe, M., Ju, Z., Kestler, H. A., Sanoff, H., et al. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00583.x · Cited by 163 · see citing works
Cytomegalovirus Infection Reduces Telomere Length of the Circulating T Cell Pool
van de Berg, P. J. E. J., Griffiths, S. J., Yong, S.-L., Macaulay, R., Bemelman, F. J., Jackson, S., Henson, S. M., ten Berge, I. J. M., Akbar, A. N., & van Lier, R. A. W. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903442 · Cited by 157 · see citing works
Self-citationPhadwal, K., Alegre-Abarrategui, J., Watson, A. S., Pike, L., Anbalagan, S., Hammond, E. M., Wade-Martins, R., McMichael, A., Klenerman, P., & Simon, A. K. (2012) · Autophagy · doi:10.4161/auto.18935 · Cited by 155 · see citing works
Self-citationTelomere dysfunction, autoimmunity and aging.
(2011) · Europe PMC (PubMed Central) · Cited by 138 · see citing works
New insights into the function of Atg9
Webber, J. L., & Tooze, S. A. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.020 · Cited by 123 · see citing works
Self-citationOxygen free radicals in cell senescence: Are they signal transducers?
Passos, J. F., & Von Zglinicki, T. (2006) · Free Radical Research · doi:10.1080/10715760600917151 · Cited by 122 · see citing works
Direct measurement of T cell subset kinetics in vivo in elderly men and women
Wallace, D. L., Zhang, Y., Ghattas, H., Worth, A., Irvine, A., Bennett, A. R., Griffin, G. E., Beverley, P. C. L., Tough, D. F., & Macallan, D. C. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.1787 · Cited by 115 · see citing works
Dagarag, M. D., Evazyan, T., Rao, N. P., & Effros, R. B. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.10.6303 · Cited by 107 · see citing works
Valmori, D., Scheibenbogen, C., Dutoit, V., Nagorsen, D., Asemissen, A. M., Rubio‐Godoy, V., Rimoldi, D., Guillaume, P., Romero, P. J., Schadendorf, D., et al. (2002) · PubMed · Cited by 106 · see citing works
Plunkett, F. J., Franzese, O., Belaramani, L. L., Fletcher, J. M., Gilmour, K. C., Sharifi, R., Khan, N., Hislop, A. D., Cara, A., Salmon, M., et al. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.006 · Cited by 74 · see citing works
Self-citationAltman, B. J., Wofford, J. A., Zhao, Y., Coloff, J. L., Ferguson, E. C., Wieman, H. L., Swearingen, A. E. D. V., Ilkayeva, O., & Rathmell, J. C. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-08-0829 · Cited by 65 · see citing works
Proliferative arrest and cell cycle regulation in CD8+CD28− versus CD8+CD28+ T cells
Scheuring, U. J., Sabzevari, H., & Theofilopoulos, A. N. (2002) · Human Immunology · doi:10.1016/s0198-8859(02)00683-3 · Cited by 59 · see citing works
Telomere loss, senescence, and genetic instability in CD4+ T lymphocytes overexpressing hTERT
Röth, A., Baerlocher, G. M., Schertzer, M., Chavez, E. A., Dührsen, U., & Lansdorp, P. M. (2005) · Blood · doi:10.1182/blood-2004-10-4144 · Cited by 57 · see citing works
Increased mitochondrial mass characterizes the survival defect of HIV-specific CD8+ T cells
Petrovas, C., Mueller, Y. M., Dimitriou, I. D., Altork, S. R., Banerjee, A., Sklar, P. A., Mounzer, K., Altman, J. D., & Katsikis, P. D. (2006) · Blood · doi:10.1182/blood-2006-05-021626 · Cited by 50 · see citing works
Reversal of functional defects in highly differentiated young and old CD8 T cells by PDL blockade
Henson, S. M., Macaulay, R., Franzese, O., & Akbar, A. N. (2012) · Immunology · doi:10.1111/j.1365-2567.2011.03550.x · Cited by 42 · see citing works
Self-citationThe road to recovery: translating PD-1 biology into clinical benefit
Riley, J. L., & June, C. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.12.001 · Cited by 30 · see citing works
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Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?
Fulop, T., Larbi, A., Dupuis, G., Le Page, A., Frost, E. H., Cohen, A. A., Witkowski, J. M., & Franceschi, C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01960 · Cited by 1,364 · see citing works
Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines
Rea, I. M., Gibson, D. S., McGilligan, V., McNerlan, S. E., Alexander, H. D., & Ross, O. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00586 · Cited by 1,267 · see citing works
Immunosenescence: molecular mechanisms and diseases
Liu, Z., Liang, Q., Ren, Y., Guo, C., Ge, X., Wang, L., Cheng, Q., Luo, P., Zhang, Y., & Han, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01451-2 · Cited by 1,023 · see citing works
Mittelbrunn, M., & Kroemer, G. (2021) · Nature Immunology · doi:10.1038/s41590-021-00927-z · Cited by 702 · see citing works
Aiello, A., Farzaneh, F., Candore, G., Caruso, C., Davinelli, S., Gambino, C. M., Ligotti, M. E., Zareian, N., & Accardi, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02247 · Cited by 693 · see citing works
Campbell, J. P., & Turner, J. E. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00648 · Cited by 692 · see citing works
Autophagy and autophagy-related proteins in the immune system
Shibutani, S., Saitoh, T., Nowag, H., Münz, C., & Yoshimori, T. (2015) · Nature Immunology · doi:10.1038/ni.3273 · Cited by 581 · see citing works
Mechanisms underlying T cell ageing
Goronzy, J. J., & Weyand, C. M. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0180-1 · Cited by 506 · see citing works
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
Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis
Cadwell, K. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.100 · Cited by 478 · see citing works
Aging of the immune system: Focus on inflammation and vaccination
Pinti, M., Appay, V., Campisi, J., Frasca, D., Fülöp, T., Sauce, D., Larbi, A., Weinberger, B., & Cossarizza, A. (2016) · European Journal of Immunology · doi:10.1002/eji.201546178 · Cited by 439 · see citing works
Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment
Zhao, Y., Shao, Q., & Peng, G. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0344-8 · Cited by 382 · see citing works
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 · see citing works
Tumour burden and efficacy of immune-checkpoint inhibitors
Dall’Olio, F. G., Marabelle, A., Caramella, C., Garcia, C., Aldea, M., Chaput, N., Robert, C., & Besse, B. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00564-3 · Cited by 350 · see citing works
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 348 · see citing works
CD57 in human natural killer cells and T-lymphocytes
Kared, H., Martelli, S., Ng, T. P., Pender, S. L. F., & Larbi, A. (2016) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-016-1803-z · Cited by 309 · see citing works
Metabolic adaptation of lymphocytes in immunity and disease
Chapman, N. M., & Chi, H.-B. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.012 · Cited by 263 · see citing works
Senescence of T Lymphocytes: Implications for Enhancing Human Immunity
Akbar, A. N., Henson, S. M., & Lanna, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.09.002 · Cited by 285 · see citing works
Self-citationA sestrin-dependent Erk–Jnk–p38 MAPK activation complex inhibits immunity during aging
Lanna, A., Gomes, D. C. O., Muller-Durovic, B., McDonnell, T., Escors, D., Gilroy, D. W., Lee, J. H., Karin, M., & Akbar, A. N. (2017) · Nature Immunology · doi:10.1038/ni.3665 · Cited by 284 · see citing works
Self-citationImmune Senescence, Immunosenescence and Aging
Lee, K.-A., Flores, R. R., Jang, I. H., Saathoff, A., & Robbins, P. D. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.900028 · Cited by 283 · see citing works
Human CD 8 + EMRA T cells display a senescence‐associated secretory phenotype regulated by p38 MAPK
Callender, L. A., Carroll, E. C., Beal, R. W. J., Chambers, E. S., Nourshargh, S., Akbar, A. N., & Henson, S. M. (2017) · Aging Cell · doi:10.1111/acel.12675 · Cited by 265 · see citing works
Self-citationSchurich, A., Pallett, L. J., Jajbhay, D., Wijngaarden, J. E., Otano, I., Gill, U. S., Hansi, N. K., Kennedy, P. T. F., Nastouli, E., Gilson, R. J. C., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.078 · Cited by 258 · see citing works
Self-citationTargeting autophagy to overcome drug resistance: further developments
Chang, H., & Zou, Z. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01000-2 · Cited by 252 · see citing works
Sestrins induce natural killer function in senescent-like CD8+ T cells
Pereira, B. I., Maeyer, R. P. H. D., Covre, L. P., Nehar-Belaid, D., Lanna, A., Ward, S., Marcheş, R., Chambers, E. S., Gomes, D. C. O., Riddell, N. E., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0643-3 · Cited by 247 · see citing works
Self-citationMoro‐García, M. A., Mayo, J. C., Sainz, R. M., & Alonso‐Arias, R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00339 · Cited by 232 · see citing works
Targeting immune dysfunction in aging
Borgoni, S., Kudryashova, K. S., Burka, K., & de Magalhães, J. P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101410 · Cited by 227 · see citing works
Cellular senescence: Immunosurveillance and future immunotherapy
Burton, D. G. A., & Stolzing, A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.02.001 · Cited by 221 · see citing works
Knaus, H. A., Berglund, S., Hackl, H., Blackford, A. L., Zeidner, J. F., Montiel-Esparza, R., Mukhopadhyay, R., Vanura, K., Blazar, B. R., Karp, J. E., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120974 · Cited by 216 · see citing works
Martínez‐Zamudio, R. I., Dewald, H. K., Vasilopoulos, T., Gittens‐Williams, L., Fitzgerald‐Bocarsly, P., & Herbig, U. (2021) · Aging Cell · doi:10.1111/acel.13344 · Cited by 213 · see citing works
T-cell Exhaustion in Multiple Myeloma Relapse after Autotransplant: Optimal Timing of Immunotherapy
Chung, D. J., Pronschinske, K. B., Shyer, J. A., Sharma, S., Leung, S., Curran, S. A., Lesokhin, A. M., Devlin, S. M., Giralt, S., & Young, J. W. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0055 · Cited by 210 · see citing works
Cellular senescence: Molecular mechanisms and pathogenicity
Wei, W., & Ji, S. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26956 · Cited by 205 · see citing works
T‐cell metabolism governing activation, proliferation and differentiation; a modular view
Dimeloe, S., Burgener-Gasser, A.-V., Grählert, J., & Hess, C. (2016) · Immunology · doi:10.1111/imm.12655 · Cited by 200 · see citing works
Suen, H., Brown, R. D., Yang, S. S., Weatherburn, C., Ho, P. J., Woodland, N., Nassif, N. T., Barbaro, P., Bryant, C. E., Hart, D. N. J., et al. (2016) · Leukemia · doi:10.1038/leu.2016.84 · Cited by 201 · see citing works
The Cellular and Molecular Basis of Translational Immunometabolism.
Norata, G., Caligiuri, G., Chavakis, T., Matarese, G., Netea, M., Nicoletti, A., O'Neill, L., & Marelli-Berg, F. (2015) · Immunity · doi:10.1016/j.immuni.2015.08.023 · Cited by 191 · see citing works
Age-associated remodeling of T cell immunity and metabolism
Han, S., Georgiev, P., Ringel, A. E., Sharpe, A. H., & Haigis, M. C. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.11.005 · Cited by 193 · see citing works
Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection
Tu, W., & Rao, S. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.02111 · Cited by 189 · see citing works
Nicolini, A., & Ferrari, P. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1353787 · Cited by 187 · see citing works
Pangrazzi, L., & Weinberger, B. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110887 · Cited by 180 · see citing works
Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives
Zhang, M., Salas, S. S., Damba, T., Borghesan, M., Demaria, M., & Moshage, H. J. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111572 · Cited by 180 · see citing works
Autophagy and skin wound healing
Ren, H., Zhao, F., Zhang, Q., Huang, X., & Wang, Z. (2022) · Burns & Trauma · doi:10.1093/burnst/tkac003 · Cited by 176 · see citing works
Senescent T cells: a potential biomarker and target for cancer therapy
Zhang, J., He, T., Xue, L., & Guo, H. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103409 · Cited by 171 · see citing works
Mitochondrial mass governs the extent of human T cell senescence
Callender, L. A., Carroll, E. C., Bober, E., Akbar, A. N., Solito, E., & Henson, S. M. (2019) · Aging Cell · doi:10.1111/acel.13067 · Cited by 167 · see citing works
Self-citationFrasca, D., Diaz, A., Romero, M., & Blomberg, B. B. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2016.12.001 · Cited by 160 · see citing works
Effects of altered glycolysis levels on CD8+ T cell activation and function
Cao, J., Liao, S., Zeng, F., Liao, Q., Luo, G., & Zhou, Y. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05937-3 · Cited by 164 · see citing works
Ferrara, R., Mezquita, L., Auclin, E., Chaput, N., & Besse, B. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.08.003 · Cited by 163 · see citing works
Immunosenescence: Aging and Immune System Decline
Goyani, P., Christodoulou, R. C., & Vassiliou, E. K. (2024) · Vaccines · doi:10.3390/vaccines12121314 · Cited by 177 · see citing works
Immunosenescence and inflammaging: Mechanisms and role in diseases
Ajoolabady, A., Praticò, D., Tang, D., Zhou, S., Franceschi, C., & Ren, J. T. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102540 · Cited by 159 · see citing works
Reduced naïve <scp>CD</scp> 8 <sup>+</sup> <scp>T</scp> ‐cell priming efficacy in elderly adults
Briceño, O., Lissina, A., Wanke, K., Afonso, G., Braun, A., Ragon, K., Miquel, T., Gostick, E., Papagno, L., Stiasny, K., et al. (2016) · Aging Cell · doi:10.1111/acel.12384 · Cited by 151 · see citing works
The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities
Sun, Y., Wang, X., Liu, T., Zhu, X., & Pan, X. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00815-5 · Cited by 151 · see citing works
Henson, S. M., Macaulay, R., Riddell, N. E., Nunn, C. J., & Akbar, A. N. (2015) · European Journal of Immunology · doi:10.1002/eji.201445312 · Cited by 146 · see citing works
Self-citationWu, Y., Li, Z., Dong, L., Li, W., Wu, Y., Wang, J., Chen, H.-P., Liu, H., Li, M., Jin, C., et al. (2019) · Autophagy · doi:10.1080/15548627.2019.1628536 · Cited by 144 · see citing works
Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1
Jeng, M. Y., Hull, P. A., Fei, M., Kwon, H.-S., Tsou, C.-L., Kasler, H., Ng, C.-P., Gordon, D. E., Johnson, J., Krogan, N., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20161066 · Cited by 121 · see citing works
Ionizing radiation-induced cellular senescence promotes tissue fibrosis after radiotherapy. A review
Nguyen, H. Q., To, N. H., Zadigue, P., Kerbrat, S., TAILLE, A. D. L., Gouvello, S. L., & Belkacémi, Y. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.06.012 · Cited by 123 · see citing works
Salminen, A. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02123-w · Cited by 124 · see citing works
The characterization of varicella zoster virus-specific T cells in skin and blood during aging
Vukmanovic-Stejic, M., Sandhu, D., Seidel, J. A., Patel, N., Sobande, T. O., Agius, E., Jackson, S. E., Fuentes-Duculan, J., Suárez-Fariñas, M., Mabbott, N. A., et al. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.63 · Cited by 117 · see citing works
Self-citationType 2 diabetes is associated with the accumulation of senescent T cells
Lau, E. Y. M., Carroll, E. C., Callender, L. A., Hood, G., Berryman, V., Pattrick, M., Finer, S., Hitman, G. A., Ackland, G. L., & Henson, S. M. (2019) · Clinical & Experimental Immunology · doi:10.1111/cei.13344 · Cited by 116 · see citing works
Self-citationIs immunosenescence influenced by our lifetime “dose” of exercise?
Turner, J. E. (2016) · Biogerontology · doi:10.1007/s10522-016-9642-z · Cited by 112 · see citing works
Autophagy Function and Regulation in Kidney Disease
Kaushal, G. P., Chandrashekar, K., Juncos, L. A., & Shah, S. V. (2020) · Biomolecules · doi:10.3390/biom10010100 · Cited by 111 · see citing works
Basic science and pathogenesis of ageing with HIV
Lagathu, C., Cossarizza, A., Béréziat, V., Nasi, M., Capeau, J., & Pinti, M. (2017) · AIDS · doi:10.1097/qad.0000000000001441 · Cited by 108 · see citing works
Expansion and Cell-Cycle Arrest: Common Denominators of Cellular Senescence
Ogrodnik, M., Salmonowicz, H., Jurk, D., & Passos, J. F. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.06.011 · Cited by 104 · see citing works
Convergence of Innate and Adaptive Immunity during Human Aging
Pereira, B. I., & Akbar, A. N. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00445 · Cited by 106 · see citing works
Self-citationLoschinski, R., Böttcher, M., Stoll, A., Bruns, H., Mackensen, A., & Mougiakakos, D. (2018) · Oncotarget · doi:10.18632/oncotarget.24442 · Cited by 106 · see citing works
Maternal and fetal T cells in term pregnancy and preterm labor
Miller, D., Gershater, M., Slutsky, R., Romero, R. J., & Gomez‐Lopez, N. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0471-2 · Cited by 104 · see citing works
Angin, M., Volant, S., Passaes, C., Lécuroux, C., Monceaux, V., Dillies, M., Valle‐Casuso, J. C., Pancino, G., Vaslin, B., Grand, R. L., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0081-4 · Cited by 103 · see citing works
T Cell Fitness and Autologous CAR T Cell Therapy in Haematologic Malignancy
Mehta, P. H., Fiorenza, S., Koldej, R. M., Jaworowski, A., Ritchie, D. S., & Quinn, K. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.780442 · Cited by 98 · see citing works
Interleukin-7 and Immunosenescence
Nguyen, V., Mendelsohn, A., & Larrick, J. W. (2017) · Journal of Immunology Research · doi:10.1155/2017/4807853 · Cited by 96 · see citing works
Rutella, S., Vadakekolathu, J. N., Mazziotta, F., Reeder, S., Yau, T. O., Mukhopadhyay, R., Dickins, B., Altmann, H., Krämer, M., Knaus, H. A., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci159579 · Cited by 96 · see citing works
Cellular senescence: from growth arrest to immunogenic conversion
Burton, D. G. A., & Faragher, R. (2015) · AGE · doi:10.1007/s11357-015-9764-2 · Cited by 95 · see citing works
The role of senescent T cells in immunopathology
Covre, L. P., De Maeyer, R. P. H., Gomes, D. C. O., & Akbar, A. N. (2020) · Aging Cell · doi:10.1111/acel.13272 · Cited by 93 · see citing works
Self-citationThe Mucosal Immune System and Its Regulation by Autophagy
Kabat, A. M., Pott, J., & Maloy, K. J. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00240 · Cited by 93 · see citing works
Autophagy and Immune Senescence
Zhang, H., Puleston, D. J., & Simon, A. K. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.06.001 · Cited by 93 · see citing works
Self-citationT Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease
Shirakawa, K., & Sano, M. (2021) · Cells · doi:10.3390/cells10092435 · Cited by 87 · see citing works
Metabolic requirements of human pro-inflammatory B cells in aging and obesity
Frasca, D., Diaz, A., Romero, M., Thaller, S. R., & Blomberg, B. B. (2019) · PLoS ONE · doi:10.1371/journal.pone.0219545 · Cited by 86 · see citing works
Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases
Yang, B., Lin, Y., Huang, Y., Shen, Y.-Q., & Chen, Q. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103032 · Cited by 90 · see citing works
Nair, R., Somasundaram, V., Kuriakose, A., Krishn, S. R., Raben, D., Salazar, R. L., & Nair, P. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1548234 · Cited by 90 · see citing works
Cellular senescence: Implications for metabolic disease
Schafer, M. J., Miller, J. D., & LeBrasseur, N. K. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.08.047 · Cited by 84 · see citing works
Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation
Jones, N., Cronin, J., Dolton, G. M., Panetti, S., Schauenburg, A. J. A., Galloway, S. A. E., Sewell, A. K., Cole, D. K., Thornton, C. A., & Francis, N. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01516 · Cited by 83 · see citing works
Host Resistance and Immune Aging
Bandaranayake, T., & Shaw, A. C. (2016) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2016.02.007 · Cited by 85 · see citing works
Frasca, D. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2017.07.002 · Cited by 82 · see citing works
Chang, K., Kang, P., Liu, Y., Huang, K., Miao, T., Sagona, A. P., Nezis, I. P., Bodmer, R., Ocorr, K. A., & Bai, H. (2019) · Autophagy · doi:10.1080/15548627.2019.1704117 · Cited by 82 · see citing works
Chen, J., Kelley, W. J., & Goldstein, D. R. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000380 · Cited by 80 · see citing works
Interactions between Autophagy and Inhibitory Cytokines
Wu, T., Li, W., & Yao, Y.-M. (2016) · International Journal of Biological Sciences · doi:10.7150/ijbs.15194 · Cited by 82 · see citing works
Wang, Q., & Ren, J. T. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.06.024 · Cited by 81 · see citing works
Role of Autophagy in Lung Inflammation
Painter, J. D., Galle-Treger, L., & Akbari, O. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01337 · Cited by 79 · see citing works
Nicholas, D., Proctor, E. A., Raval, F., Ip, B. C., Habib, C., Ritou, E., Grammatopoulos, T. N., Steenkamp, D., Dooms, H., Apovian, C. M., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170975 · Cited by 77 · see citing works
Epigenomic drivers of immune dysfunction in aging
Keenan, C. R., & Allan, R. S. (2018) · Aging Cell · doi:10.1111/acel.12878 · Cited by 76 · see citing works
Modulation of Autophagy for Controlling Immunity
Jang, Y. J., Kim, J. H., & Byun, S. (2019) · Cells · doi:10.3390/cells8020138 · Cited by 74 · see citing works
The role of autophagy in colitis-associated colorectal cancer
Wu, Y., Yao, J., Xie, J., Liu, Z., Zhou, Y., Pan, H., & Han, W. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-018-0031-8 · Cited by 74 · see citing works
IL-15 in T-Cell Responses and Immunopathogenesis
Lee, H., Park, S., & Shin, E. (2024) · Immune Network · doi:10.4110/in.2024.24.e11 · Cited by 73 · see citing works
The senescence journey in cancer immunoediting
Zingoni, A., Antonangeli, F., Sozzani, S., Santoni, A., Cippitelli, M., & Soriani, A. (2024) · Molecular Cancer · doi:10.1186/s12943-024-01973-5 · Cited by 74 · see citing works
The effects of age and systemic metabolism on anti-tumor T cell responses
Drijvers, J. M., Sharpe, A. H., & Haigis, M. C. (2020) · eLife · doi:10.7554/elife.62420 · Cited by 69 · see citing works
“Furthermore, aged memory CD8 T cells may have increased mTOR activity and glycolysis well as a reduced ability to engage in autophagy (Davenport et al., 2019; Henson et al., 2014), while newly activated aged CD4 T cells fail to”
BackgroundAutophagy in T Cell Function and Aging
Macián, F. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00213 · Cited by 69 · see citing works
Activation of G protein‐coupled receptor 30 protects neurons by regulating autophagy in astrocytes
Wang, X., Yue, J., Hu, L., Tian, Z., Zhang, K., Yang, L., Zhang, H., Guo, Y., Feng, B., Liu, H., et al. (2019) · Glia · doi:10.1002/glia.23697 · Cited by 71 · see citing works
Bonney, E. A. (2017) · American Journal of Reproductive Immunology · doi:10.1111/aji.12652 · Cited by 67 · see citing works
Turner, J. E., & Brum, P. C. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/4234765 · Cited by 65 · see citing works
Jin, J., Mu, Y., Zhang, H., Sturmlechner, I., Wang, C., Jadhav, R. R., Xia, Q., Weyand, C. M., & Goronzy, J. J. (2023) · Nature Aging · doi:10.1038/s43587-023-00399-w · Cited by 64 · see citing works
Assessing immune aging in HIV-infected patients
Appay, V., & Sauce, D. (2016) · Virulence · doi:10.1080/21505594.2016.1195536 · Cited by 65 · see citing works
Zhao, L., Lan, Z., Peng, L., Wan, L., Liu, D., Tan, X., Tang, C., Chen, G., & Liu, H. (2022) · Cell Proliferation · doi:10.1111/cpr.13278 · Cited by 64 · see citing works
Senescence and the Aging Immune System as Major Drivers of Chronic Kidney Disease
Schroth, J., Thiemermann, C., & Henson, S. M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.564461 · Cited by 59 · see citing works
Self-citationPI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling
Thürmer, M., Gollowitzer, A., Pein, H., Neukirch, K., Gelmez, E., Waltl, L., Wielsch, N., Winkler, R., Loeser, K., Grander, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30374-9 · Cited by 62 · see citing works
- Authors
- Henson, S. M., Lanna, A., Riddell, N. E., Franzese, O., Macaulay, R., Griffiths, S. J., Puleston, D. J., Watson, A. S., Simon, A. K., Tooze, S. A., & Akbar, A. N.
- Affiliations
- University College London (GB)
- University of Rome Tor Vergata (IT)
- University of Oxford (GB)
- Cancer Research UK (GB)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2014-08-01
- Volume
- 124
- Issue
- 9
- Pages
- 4004-4016
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4151208
- OpenAlex
- W1976615668
- Cited by
- 389
- References
- 60
- Citations by year
- 2026: 29 · 2025: 49 · 2024: 42 · 2023: 33 · 2022: 37 · 2021: 39 · 2020: 28 · 2019: 31 · 2018: 27 · 2017: 27 · 2016: 32 · 2015: 13 · 2014: 2
- FWCI
- 16.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Cancer Research UK (15153)
- National Institute for Health and Care Research
- University College London
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/J006750/1, BB/G021422/1)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- T cell senescence, CD8+ T cells, p38 MAPK signaling, mTOR-independent autophagy, Atg9, CD45RA, effector memory T cells, mitochondrial biogenesis, anaerobic glycolysis, telomerase activity, cytotoxicity, immunosenescence, T cell metabolism
- MeSH terms
- Autophagy-Related Proteins, Mechanistic Target of Rapamycin Complex 1, Adult, Autophagy, DNA Damage, Glycolysis, Humans, Membrane Proteins, Mitochondria, Oxidative Phosphorylation, Cellular Senescence, CD8-Positive T-Lymphocytes, MAP Kinase Signaling System, Vesicular Transport Proteins, Multiprotein Complexes, p38 Mitogen-Activated Protein Kinases, Membrane Potential, Mitochondrial, TOR Serine-Threonine Kinases
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.
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