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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2020

Open Access 01-12-2020 | Cancer Immunotherapy | Review

Immunosenescence: a key player in cancer development

Authors: Jingyao Lian, Ying Yue, Weina Yu, Yi Zhang

Published in: Journal of Hematology & Oncology | Issue 1/2020

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Abstract

Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumors. 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. Senescent T cells exhibit abnormal phenotypes, including downregulation of CD27, CD28, and upregulation of CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, and cytotoxic T-lymphocyte-associated protein 4, which are tightly related to malignant tumors. The role of immunosenescence in tumors is sophisticated: the many factors involved include cAMP, glucose competition, and oncogenic stress in the tumor microenvironment, which can induce the senescence of T cells, macrophages, natural killer cells, and dendritic cells. Accordingly, these senescent immune cells could also affect tumor progression. In addition, the effect of immunosenescence on the response to immune checkpoint blocking antibody therapy so far is ambiguous due to the low participation of elderly cancer patients in clinical trials. Furthermore, many other senescence-related interventions could be possible with genetic and pharmacological methods, including mTOR inhibition, interleukin-7 recombination, and NAD+ activation. Overall, this review aims to highlight the characteristics of immunosenescence and its impact on malignant tumors and immunotherapy, especially the future directions of tumor treatment through senescence-focused strategies.
Literature
1.
2.
Hsu T. Educational initiatives in geriatric oncology - Who, why, and how? J Geriat Oncol. 2016;7(5):390–6. CrossRef
3.
Munoz-Espin D, Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol. 2014;15(7):482–96. PubMedCrossRef
4.
Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, Campisi J, Collado M, Evangelou K, Ferbeyre G, et al. Cellular senescence: defining a path forward. Cell. 2019;179(4):813–27. PubMedCrossRef
5.
6.
Nacarelli T, Lau L, Fukumoto T, Zundell J, Fatkhutdinov N, Wu S, Aird KM, Iwasaki O, Kossenkov AV, Schultz D, et al. NAD metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol. 2019;21(3):397–407. PubMedPubMedCentralCrossRef
7.
Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007;130(2):223–33. PubMedCrossRef
8.
Yang L, Li A, Lei Q, Zhang Y. Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment. J Hematol Oncol. 2019;12(1):125. PubMedPubMedCentralCrossRef
9.
10.
11.
Pawelec G. Immunosenescence comes of age. Symposium on Aging Research in Immunology: The Impact of Genomics. EMBO Rep. 2007;8(3):220–3.
12.
13.
Caruso C, Accardi G, Virruso C, Candore G. Sex, gender and immunosenescence: a key to understand the different lifespan between men and women? Immun Ageing. 2013;10(1):20. PubMedPubMedCentralCrossRef
14.
15.
16.
Aiello A, Accardi G, Candore G, Caruso C, Colomba C, Di Bona D, Duro G, Gambino CM, Ligotti ME, Pandey JP. Role of Immunogenetics in the Outcome of HCMV Infection: Implications for Ageing. Int J Mol Sci. 2019;20(3):685. PubMedCentralCrossRef
17.
18.
Fane M, Weeraratna AT. How the ageing microenvironment influences tumour progression. Nat Rev Cancer. 2020;20(2):89–106. PubMedCrossRef
19.
Su D-M, Aw D, Palmer DB. Immunosenescence: a product of the environment? Curr Opin Immunol. 2013;25(4):498–503. PubMedCrossRef
20.
Nikolich-Žugich J. Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories. J Immunol. 2014;193(6):2622–9. PubMedCrossRef
21.
Nikolich-Zugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018;19(1):10–9. PubMedCrossRef
22.
23.
Pinti M, Appay V, Campisi J, Frasca D, Fülöp T, Sauce D, Larbi A, Weinberger B, Cossarizza A. Aging of the immune system: Focus on inflammation and vaccination. Eur J Immunol. 2016;46(10):2286–301. PubMedPubMedCentralCrossRef
24.
Palmer S, Albergante L, Blackburn CC, Newman TJ. Thymic involution and rising disease incidence with age. Proc Natl Acad Sci U S A. 2018;115(8):1883–8. PubMedPubMedCentralCrossRef
25.
26.
Cancro MP, Hao Y, Scholz JL, Riley RL, Frasca D, Dunn-Walters DK, Blomberg BB. B cells and aging: molecules and mechanisms. Trends Immunol. 2009;30(7):313–8. PubMedPubMedCentralCrossRef
27.
Akbar AN, Henson SM. Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat Rev Immunol. 2011;11(4):289–95. PubMedCrossRef
28.
Hazeldine J, Lord JM. Innate immunosenescence: underlying mechanisms and clinical relevance. Biogerontology. 2015;16(2):187–201. PubMedCrossRef
29.
Masters AR, Haynes L, Su DM, Palmer DB. Immune senescence: significance of the stromal microenvironment. Clin Exp Immunol. 2017;187(1):6–15. PubMedCrossRef
30.
31.
Crespo J, Sun H, Welling TH, Tian Z, Zou W. T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment. Curr Opin Immunol. 2013;25(2):214–21. PubMedPubMedCentralCrossRef
32.
Yang OO, Lin H, Dagarag M, Ng HL, Effros RB, Uittenbogaart CH. Decreased perforin and granzyme B expression in senescent HIV-1-specific cytotoxic T lymphocytes. Virology. 2005;332(1):16–9. PubMedCrossRef
33.
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 1995;92(20):9363–7. PubMedCrossRefPubMedCentral
34.
Debacq-Chainiaux F, Erusalimsky JD, Campisi J, Toussaint O. Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protoc. 2009;4(12):1798–806. PubMedCrossRef
35.
Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, Karoly ED, Freeman GJ, Petkova V, Seth P, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun. 2015;6:6692. PubMedCrossRef
36.
Henson SM, Lanna A, Riddell NE, Franzese O, Macaulay R, Griffiths SJ, Puleston DJ, Watson AS, Simon AK, Tooze SA, et al. p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells. J Clin Invest. 2014;124(9):4004–16. PubMedPubMedCentralCrossRef
37.
Sun Y, Coppé J-P, Lam EWF. Cellular senescence: the sought or the unwanted? Trend Mol Med. 2018;24(10):871–85. CrossRef
38.
Larbi A, Fulop T. From, “truly naïve” to “exhausted senescent” T cells: when markers predict functionality. Cytometry A. 2014;85(1):25–35. PubMedCrossRef
39.
Zhao Y, Shao Q, Peng G. Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment. Cell Mol Immunol. 2020;17(1):27–35. PubMedCrossRef
40.
41.
Huff WX, Kwon JH, Henriquez M, Fetcko K, Dey M. The evolving role of CD8CD28 Immunosenescent T cells in cancer immunology. Int J Mol Sci. 2019;20(11):2810. PubMedCentralCrossRef
42.
Mondal AM, Horikawa I, Pine SR, Fujita K, Morgan KM, Vera E, Mazur SJ, Appella E, Vojtesek B, Blasco MA, et al. p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes. J Clin Invest. 2013;123(12):5247–57. PubMedPubMedCentralCrossRef
43.
Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Ibrahim JG, Thomas NE, Sharpless NE. Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell. 2009;8(4):439–48. PubMedCrossRef
44.
Bernadotte A, Mikhelson VM, Spivak IM. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. Aging. 2016;8(1):3–11. PubMedPubMedCentralCrossRef
45.
Manser AR, Uhrberg M. Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance. Cancer Immunol Immunother. 2016;65(4):417–26. PubMedCrossRef
46.
Sanchez-Correa B, Campos C, Pera A, Bergua JM, Arcos MJ, Banas H, Casado JG, Morgado S, Duran E, Solana R, et al. Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies? Cancer Immunol Immunother. 2016;65(4):453–63. PubMedCrossRef
47.
Tahir S, Fukushima Y, Sakamoto K, Sato K, Fujita H, Inoue J, Uede T, Hamazaki Y, Hattori M, Minato N. A CD153+CD4+ T follicular cell population with cell-senescence features plays a crucial role in lupus pathogenesis via osteopontin production. J Immunol. 2015;194(12):5725–35. PubMedCrossRef
48.
Wang Y-H, Yu X-H, Luo S-S, Han H. Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing. Immun Ageing. 2015;12:17. PubMedPubMedCentralCrossRef
49.
DeSantis CE, Miller KD, Dale W, Mohile SG, Cohen HJ, Leach CR, Goding Sauer A, Jemal A, Siegel RL. Cancer statistics for adults aged 85 years and older, 2019. CA: a cancer journal for clinicians. 2019;69(6):452–67.
50.
Pelissier Vatter FA, Schapiro D, Chang H, Borowsky AD, Lee JK, Parvin B, Stampfer MR, LaBarge MA, Bodenmiller B, Lorens JB. High-dimensional phenotyping identifies age-emergent cells in human mammary epithelia. Cell Rep. 2018;23(4):1205–19. PubMedPubMedCentralCrossRef
51.
Ye J, Huang X, Hsueh EC, Zhang Q, Ma C, Zhang Y, Varvares MA, Hoft DF, Peng G. Human regulatory T cells induce T-lymphocyte senescence. Blood. 2012;120(10):2021–31. PubMedPubMedCentralCrossRef
52.
Ye J, Ma C, Hsueh EC, Eickhoff CS, Zhang Y, Varvares MA, Hoft DF, Peng G. Tumor-derived γδ regulatory T cells suppress innate and adaptive immunity through the induction of immunosenescence. J Immunol. 2013;190(5):2403–14. PubMedCrossRef
53.
Liu X, Mo W, Ye J, Li L, Zhang Y, Hsueh EC, Hoft DF, Peng G. Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition. Nat Commun. 2018;9(1):249. PubMedPubMedCentralCrossRef
54.
Wang D, Yang L, Yue D, Cao L, Li L, Wang D, Ping Y, Shen Z, Zheng Y, Wang L, et al. Macrophage-derived CCL22 promotes an immunosuppressive tumor microenvironment via IL-8 in malignant pleural effusion. Cancer Lett. 2019;452:244–53. PubMedCrossRef
55.
56.
Sitkovsky MV, Kjaergaard J, Lukashev D, Ohta A. Hypoxia-adenosinergic immunosuppression: tumor protection by T regulatory cells and cancerous tissue hypoxia. Clin Cancer Res. 2008;14(19):5947–52. PubMedCrossRef
57.
Vang T, Torgersen KM, Sundvold V, Saxena M, Levy FO, Skålhegg BS, Hansson V, Mustelin T, Taskén K. Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor. J Exp Med. 2001;193(4):497–507. PubMedPubMedCentralCrossRef
58.
Salminen A, Kauppinen A, Kaarniranta K. Myeloid-derived suppressor cells (MDSC): an important partner in cellular/tissue senescence. Biogerontology. 2018;19(5):325–39. PubMedCrossRef
59.
Wang W, Chen JX, Liao R, Deng Q, Zhou JJ, Huang S, Sun P. Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6-p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced premature senescence. Mol Cell Biol. 2002;22(10):3389–403. PubMedPubMedCentralCrossRef
60.
Freund A, Patil CK, Campisi J. p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 2011;30(8):1536–48. PubMedPubMedCentralCrossRef
61.
Van Nguyen T, Puebla-Osorio N, Pang H, Dujka ME, Zhu C. DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model. J Exp Med. 2007;204(6):1453–61. PubMedPubMedCentralCrossRef
62.
Rodier F, Coppé J-P, Patil CK, Hoeijmakers WAM, Muñoz DP, Raza SR, Freund A, Campeau E, Davalos AR, Campisi J. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009;11(8):973–9. PubMedPubMedCentralCrossRef
63.
Ye J, Ma C, Hsueh EC, Dou J, Mo W, Liu S, Han B, Huang Y, Zhang Y, Varvares MA, et al. TLR8 signaling enhances tumor immunity by preventing tumor-induced T-cell senescence. EMBO Mol Med. 2014;6(10):1294–311. PubMedPubMedCentralCrossRef
64.
Lanna A, Gomes DCO, Muller-Durovic B, McDonnell T, Escors D, Gilroy DW, Lee JH, Karin M, Akbar AN. A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging. Nat Immunol. 2017;18(3):354–63. PubMedPubMedCentralCrossRef
65.
Lanna A, Henson SM, Escors D, Akbar AN. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells. Nat Immunol. 2014;15(10):965–72. PubMedPubMedCentralCrossRef
66.
67.
Onyema OO, Decoster L, Njemini R, Forti LN, Bautmans I, De Waele M, Mets T. Chemotherapy-induced changes and immunosenescence of CD8+ T-cells in patients with breast cancer. Anticancer Res. 2015;35(3):1481–9. PubMed
68.
Sceneay J, Goreczny GJ, Wilson K, Morrow S, DeCristo MJ, Ubellacker JM, Qin Y, Laszewski T, Stover DG, Barrera V, et al. Interferon signaling is diminished with age and is associated with immune checkpoint blockade efficacy in triple-negative breast cancer. Cancer Discov. 2019;9(9):1208–27. PubMedCrossRef
69.
Ecker BL, Kaur A, Douglass SM, Webster MR, Almeida FV, Marino GE, Sinnamon AJ, Neuwirth MG, Alicea GM, Ndoye A, et al. Age-related changes in HAPLN1 increase lymphatic permeability and affect routes of melanoma metastasis. Cancer Discov. 2019;9(1):82–95. PubMedCrossRef
70.
Kaur A, Webster MR, Marchbank K, Behera R, Ndoye A, Kugel CH, Dang VM, Appleton J, O’Connell MP, Cheng P, et al. sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance. Nature. 2016;532(7598):250–4. PubMedPubMedCentralCrossRef
71.
Oh J, Magnuson A, Benoist C, Pittet MJ, Weissleder R. Age-related tumor growth in mice is related to integrin α 4 in CD8+ T cells. JCI insight. 2018;3(21):e122961. PubMedCentralCrossRef
72.
73.
Ershler WB, Socinski MA, Greene CJ. Bronchogenic cancer, metastases, and aging. J Am Geriatr Soc. 1983;31(11):673–6. PubMedCrossRef
74.
Ershler WB, Stewart JA, Hacker MP, Moore AL, Tindle BH. B16 murine melanoma and aging: slower growth and longer survival in old mice. J Natl Cancer Inst. 1984;72(1):161–4. PubMedCrossRef
75.
Pili R, Guo Y, Chang J, Nakanishi H, Martin GR, Passaniti A. Altered angiogenesis underlying age-dependent changes in tumor growth. J Natl Cancer Inst. 1994;86(17):1303–14. PubMedCrossRef
76.
77.
Gomes AP, Ilter D, Low V, Endress JE, Fernández-García J, Rosenzweig A, Schild T, Broekaert D, Ahmed A, Planque M, et al. Age-induced accumulation of methylmalonic acid promotes tumour progression. Nature. 2020;585(7824):283–7. PubMedCrossRefPubMedCentral
78.
Ruscetti M, Morris JP, Mezzadra R, Russell J, Leibold J, Romesser PB, Simon J, Kulick A, Ho Y-J, Fennell M, et al. Senescence-induced vascular remodeling creates therapeutic vulnerabilities in pancreas cancer. Cell. 2020;181(2):424-441.e21. PubMedPubMedCentralCrossRef
79.
Naumova E, Pawelec G, Mihaylova A. Natural killer cells, ageing and cancer. Cancer Immunol Immunother. 2016;65(4):367–70. PubMedCrossRef
80.
81.
Shehata HM, Hoebe K, Chougnet CA. The aged nonhematopoietic environment impairs natural killer cell maturation and function. Aging Cell. 2015;14(2):191–9. PubMedPubMedCentralCrossRef
82.
Fauriat C, Just-Landi S, Mallet F, Arnoulet C, Sainty D, Olive D, Costello RT. Deficient expression of NCR in NK cells from acute myeloid leukemia: Evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Blood. 2007;109(1):323–30. PubMedCrossRef
83.
Lakshmikanth T, Burke S, Ali TH, Kimpfler S, Ursini F, Ruggeri L, Capanni M, Umansky V, Paschen A, Sucker A, et al. NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. J Clin Invest. 2009;119(5):1251–63. PubMedPubMedCentralCrossRef
84.
Carlsten M, Björkström NK, Norell H, Bryceson Y, van Hall T, Baumann BC, Hanson M, Schedvins K, Kiessling R, Ljunggren H-G, et al. DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells. Cancer Res. 2007;67(3):1317–25. PubMedCrossRef
85.
Campos C, López N, Pera A, Gordillo JJ, Hassouneh F, Tarazona R, Solana R. Expression of NKp30, NKp46 and DNAM-1 activating receptors on resting and IL-2 activated NK cells from healthy donors according to CMV-serostatus and age. Biogerontology. 2015;16(5):671–83. PubMedCrossRef
86.
Campos C, Pera A, Sanchez-Correa B, Alonso C, Lopez-Fernandez I, Morgado S, Tarazona R, Solana R. Effect of age and CMV on NK cell subpopulations. Exp Gerontol. 2014;54:130–7. PubMedCrossRef
87.
Sanchez-Correa B, Campos C, Pera A, Bergua JM, Arcos MJ, Bañas H, Casado JG, Morgado S, Duran E, Solana R, et al. Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies? Cancer Immunol Immunother. 2016;65(4):453–63. PubMedCrossRef
88.
Tarazona R, Sanchez-Correa B, Casas-Avilés I, Campos C, Pera A, Morgado S, López-Sejas N, Hassouneh F, Bergua JM, Arcos MJ, et al. Immunosenescence: limitations of natural killer cell-based cancer immunotherapy. Cancer Immunol Immunother. 2017;66(2):233–45. PubMedCrossRef
89.
Curti A, Ruggeri L, D’Addio A, Bontadini A, Dan E, Motta MR, Trabanelli S, Giudice V, Urbani E, Martinelli G, et al. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood. 2011;118(12):3273–9. PubMedCrossRef
90.
Goronzy JJ, Fang F, Cavanagh MM, Qi Q, Weyand CM. Naive T cell maintenance and function in human aging. J Immunol. 2015;194(9):4073–80. PubMedCrossRef
91.
Qi Q, Zhang DW, Weyand CM, Goronzy JJ. Mechanisms shaping the naïve T cell repertoire in the elderly - thymic involution or peripheral homeostatic proliferation? Exp Gerontol. 2014;54:71–4. PubMedPubMedCentralCrossRef
92.
Drabkin MJ, Meyer JI, Kanth N, Lobel S, Fogel J, Grossman J, Krumenacker JH. Age-stratified patterns of thymic involution on multidetector CT. J Thorac Imaging. 2018;33(6):409–16. PubMedCrossRef
93.
94.
Rezzani R, Nardo L, Favero G, Peroni M, Rodella LF. Thymus and aging: morphological, radiological, and functional overview. Age (Dordr). 2014;36(1):313–51. CrossRef
95.
96.
97.
Fukushima Y, Minato N, Hattori M. The impact of senescence-associated T cells on immunosenescence and age-related disorders. Inflamm Regen. 2018;38:24. PubMedPubMedCentralCrossRef
98.
99.
100.
Pulko V, Davies JS, Martinez C, Lanteri MC, Busch MP, Diamond MS, Knox K, Bush EC, Sims PA, Sinari S, et al. Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses. Nat Immunol. 2016;17(8):966–75. PubMedPubMedCentralCrossRef
101.
Chiu B-C, Martin BE, Stolberg VR, Chensue SW. Cutting edge: Central memory CD8 T cells in aged mice are virtual memory cells. J Immunol. 2013;191(12):5793–6. CrossRefPubMed
102.
Quinn KM, Fox A, Harland KL, Russ BE, Li J, Nguyen THO, Loh L, Olshanksy M, Naeem H, Tsyganov K, et al. Age-related decline in primary CD8(+) T cell responses is associated with the development of senescence in virtual memory CD8(+) T cells. Cell Rep. 2018;23(12):3512–24. PubMedCrossRef
103.
Jansen CS, Prokhnevska N, Master VA, Sanda MG, Carlisle JW, Bilen MA, Cardenas M, Wilkinson S, Lake R, Sowalsky AG, et al. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature. 2019;576(7787):465–70. PubMedCrossRefPubMedCentral
104.
Held W, Siddiqui I, Schaeuble K, Speiser DE. Intratumoral CD8 T cells with stem cell-like properties: implications for cancer immunotherapy. Sci Transl Med. 2019;11(515):eaay6863.
105.
106.
Di Benedetto S, Derhovanessian E, Steinhagen-Thiessen E, Goldeck D, Müller L, Pawelec G. Impact of age, sex and CMV-infection on peripheral T cell phenotypes: results from the Berlin BASE-II Study. Biogerontology. 2015;16(5):631–43. PubMedCrossRef
107.
Ahmed R, Roger L, Costa Del Amo P, Miners KL, Jones RE, Boelen L, Fali T, Elemans M, Zhang Y, Appay V, et al. Human stem cell-like memory T cells are maintained in a state of dynamic flux. Cell reports. 2016;17(11):2811–8. PubMedCrossRef
108.
Li M, Yao D, Zeng X, Kasakovski D, Zhang Y, Chen S, Zha X, Li Y, Xu L. Age related human T cell subset evolution and senescence. Immun Ageing. 2019;16:24. PubMedPubMedCentralCrossRef
109.
Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, Wong G, Strickland M, Malleret B, Amoah A, et al. Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway. Nat Commun. 2020;11(1):821. PubMedPubMedCentralCrossRef
110.
111.
112.
113.
Lichtenegger FS, Krupka C, Haubner S, Köhnke T, Subklewe M. Recent developments in immunotherapy of acute myeloid leukemia. J Hematol Oncol. 2017;10(1):142. PubMedPubMedCentralCrossRef
114.
Wei G, Ding L, Wang J, Hu Y, Huang H. Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Exp Hematol Oncol. 2017;6:10. PubMedPubMedCentralCrossRef
115.
116.
117.
Sidaway P. Immunotherapy: CAR T cell therapy efficacious against B-ALL across age groups. Nat Rev Clin Oncol. 2018;15(4):199. PubMedCrossRef
118.
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48. PubMedPubMedCentralCrossRef
119.
Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic Leukemia. N Engl J Med. 2018;378(5):449–59. PubMedPubMedCentralCrossRef
120.
Stirrups R. CAR T-cells for relapsed B-cell ALL in children and young adults. Lancet Oncol. 2018;19(3):e144. PubMedCrossRef
121.
122.
123.
Yao D, Xu L, Tan J, Zhang Y, Lu S, Li M, Lu S, Yang L, Chen S, Chen J, et al. Re-balance of memory T cell subsets in peripheral blood from patients with CML after TKI treatment. Oncotarget. 2017;8(47):81852–9. PubMedPubMedCentralCrossRef
124.
Zhu X, Niedermann G. Rapid and efficient transfer of the T cell aging marker CD57 from glioblastoma stem cells to CAR T cells. Oncoscience. 2015;2(5):476–82. PubMedPubMedCentralCrossRef
125.
Zhu X, Prasad S, Gaedicke S, Hettich M, Firat E, Niedermann G. Patient-derived glioblastoma stem cells are killed by CD133-specific CAR T cells but induce the T cell aging marker CD57. Oncotarget. 2015;6(1):171–84. PubMedCrossRef
126.
Yang Y, Kohler ME, Chien CD, Sauter CT, Jacoby E, Yan C, Hu Y, Wanhainen K, Qin H, Fry TJ. TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and leukemic clearance. Sci Transl Med. 2017;9(417):eaag1209.
127.
Amor C, Feucht J, Leibold J, Ho Y-J, Zhu C, Alonso-Curbelo D, Mansilla-Soto J, Boyer JA, Li X, Giavridis T, et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature. 2020;583(7814):127–32. PubMedCrossRefPubMedCentral
128.
Fornara O, Odeberg J, Wolmer Solberg N, Tammik C, Skarman P, Peredo I, Stragliotto G, Rahbar A, Soderberg-Naucler C. Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery. Oncoimmunology. 2015;4(9):e1036211. PubMedPubMedCentralCrossRef
129.
Shimatani K, Nakashima Y, Hattori M, Hamazaki Y, Minato N. PD-1+ memory phenotype CD4+ T cells expressing C/EBPalpha underlie T cell immunodepression in senescence and leukemia. Proc Natl Acad Sci USA. 2009;106(37):15807–12. PubMedCrossRefPubMedCentral
130.
Fang F, Yu M, Cavanagh MM, Hutter Saunders J, Qi Q, Ye Z, Le Saux S, Sultan W, Turgano E, Dekker CL, et al. Expression of CD39 on activated T cells impairs their survival in older individuals. Cell Rep. 2016;14(5):1218–31. PubMedPubMedCentralCrossRef
131.
Elyahu Y, Hekselman I, Eizenberg-Magar I, Berner O, Strominger I, Schiller M, Mittal K, Nemirovsky A, Eremenko E, Vital A, et al. Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes. Sci Adv. 2019;5(8):eaaw8330.
132.
Kozlowska E, Biernacka M, Ciechomska M, Drela N. Age-related changes in the occurrence and characteristics of thymic CD4(+) CD25(+) T cells in mice. Immunology. 2007;122(3):445–53. PubMedPubMedCentralCrossRef
133.
Thomas DC, Mellanby RJ, Phillips JM, Cooke A. An early age-related increase in the frequency of CD4+ Foxp3+ cells in BDC2.5NOD mice. Immunology. 2007;121(4):565–76.
134.
Zhao L, Sun L, Wang H, Ma H, Liu G, Zhao Y. Changes of CD4+CD25+Foxp3+ regulatory T cells in aged Balb/c mice. J Leukoc Biol. 2007;81(6):1386–94. PubMedCrossRef
135.
Pan X-D, Mao Y-Q, Zhu L-J, Li J, Xie Y, Wang L, Zhang G-B. Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice. Chin Med J (Engl). 2012;125(11):2004–11.
136.
Gong Z, Jia Q, Chen J, Diao X, Gao J, Wang X, Zhu B. Impaired cytolytic activity and loss of clonal neoantigens in elderly patients with lung adenocarcinoma. J Thorac Oncol. 2019;14(5):857–66. PubMedCrossRef
137.
Wang S-S, Liu W, Ly D, Xu H, Qu L, Zhang L. Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer. Cell Mol Immunol. 2019;16(1):6–18. PubMedCrossRef
138.
Hagen M, Derudder E. Inflammation and the alteration of B-Cell physiology in aging. Gerontology. 2020;66(2):105–13. PubMedCrossRef
139.
140.
Bulati M, Caruso C, Colonna-Romano G. From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by “inflamm-ageing.” Ageing Res Rev. 2017;36:125–36. PubMedCrossRef
141.
Kogut I, Scholz JL, Cancro MP, Cambier JC. B cell maintenance and function in aging. Semin Immunol. 2012;24(5):342–9. PubMedCrossRef
142.
Cepeda S, Cantu C, Orozco S, Xiao Y, Brown Z, Semwal MK, Venables T, Anderson MS, Griffith AV. Age-associated decline in thymic B cell expression of aire and aire-dependent self-antigens. Cell Rep. 2018;22(5):1276–87. PubMedPubMedCentralCrossRef
143.
Johnson KM, Owen K, Witte PL. Aging and developmental transitions in the B cell lineage. Int Immunol. 2002;14(11):1313–23. PubMedCrossRef
144.
Kline GH, Hayden TA, Klinman NR. B cell maintenance in aged mice reflects both increased B cell longevity and decreased B cell generation. J Immunol. 1999;162(6):3342–9. PubMed
145.
Agrawal A, Gupta S. Impact of aging on dendritic cell functions in humans. Ageing Res Rev. 2011;10(3):336–45. PubMedCrossRef
146.
Gardner JK, Mamotte CDS, Jackaman C, Nelson DJ. Modulation of dendritic cell and T cell cross-talk during aging: the potential role of checkpoint inhibitory molecules. Ageing Res Rev. 2017;38:40–51. PubMedCrossRef
147.
Jackaman C, Tomay F, Duong L, Abdol Razak NB, Pixley FJ, Metharom P, Nelson DJ. Aging and cancer: the role of macrophages and neutrophils. Ageing Res Rev. 2017;36:105–16. PubMedCrossRef
148.
He Y-M, Li X, Perego M, Nefedova Y, Kossenkov AV, Jensen EA, Kagan V, Liu Y-F, Fu S-Y, Ye Q-J, et al. Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation. Nat Med. 2018;24(2):224–31. PubMedPubMedCentralCrossRef
149.
Salminen A, Kauppinen A, Kaarniranta K. AMPK activation inhibits the functions of myeloid-derived suppressor cells (MDSC): impact on cancer and aging. J Mol Med (Berl). 2019;97(8):1049–64. CrossRef
150.
Scher KS, Hurria A. Under-representation of older adults in cancer registration trials: known problem, little progress. J Clin Oncol. 2012;30(17):2036–8. PubMedCrossRef
151.
Mohile SG, Dale W, Somerfield MR, Hurria A. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology summary. J Oncol Pract. 2018;14(7):442–6. PubMedCrossRef
152.
Ferrara R, Mezquita L, Auclin E, Chaput N, Besse B. Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: does age really matter? Cancer Treat Rev. 2017;60:60–8. PubMedCrossRef
153.
Padron A, Hurez V, Gupta HB, Clark CA, Pandeswara SL, Yuan B, Svatek RS, Turk MJ, Drerup JM, Li R, et al. Age effects of distinct immune checkpoint blockade treatments in a mouse melanoma model. Exp Gerontol. 2018;105:146–54. PubMedCrossRefPubMedCentral
154.
Kugel CH 3rd, Douglass SM, Webster MR, Kaur A, Liu Q, Yin X, Weiss SA, Darvishian F, Al-Rohil RN, Ndoye A, et al. Age Correlates with response to Anti-PD1, reflecting age-related differences in intratumoral effector and regulatory T-cell populations. Clin Cancer Res. 2018;24(21):5347–56. PubMedPubMedCentralCrossRef
155.
Elias R, Giobbie-Hurder A, McCleary NJ, Ott P, Hodi FS, Rahma O. Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis. J Immunother Cancer. 2018;6(1):26. PubMedPubMedCentralCrossRef
156.
Li P, Yang X, Feng Y, Wu L, Ma W, Ding G, Wei Y, Sun L. The impact of immunosenescence on the efficacy of immune checkpoint inhibitors in melanoma patients: a meta-analysis. Onco Targets Ther. 2018;11:7521–7. PubMedPubMedCentralCrossRef
157.
Marur S, Singh H, Mishra-Kalyani P, Larkins E, Keegan P, Sridhara R, Blumenthal GM, Pazdur R. FDA analyses of survival in older adults with metastatic non-small cell lung cancer in controlled trials of PD-1/PD-L1 blocking antibodies. Semin Oncol. 2018;45(4):220–5. PubMedCrossRef
158.
Nishijima TF, Muss HB, Shachar SS, Moschos SJ. Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: a systematic review and meta-analysis. Cancer Treat Rev. 2016;45:30–7. PubMedCrossRef
159.
Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4(12):1721–8. PubMedPubMedCentralCrossRef
160.
Ridolfi L, De Rosa F, Petracci E, Tanda ET, Marra E, Pigozzo J, Marconcini R, Guida M, Cappellini GCA, Gallizzi G, et al. Anti-PD1 antibodies in patients aged >/= 75 years with metastatic melanoma: a retrospective multicentre study. J Geriatr Oncol. 2020;11(3):515–22. PubMedCrossRef
161.
Sekido K, Tomihara K, Tachinami H, Heshiki W, Sakurai K, Moniruzzaman R, Imaue S, Fujiwara K, Noguchi M. Alterations in composition of immune cells and impairment of anti-tumor immune response in aged oral cancer-bearing mice. Oral Oncol. 2019;99:104462. PubMedCrossRef
162.
Belgioia L, Desideri I, Errico A, Franzese C, Daidone A, Marino L, Fiore M, Borghetti P, Greto D, Fiorentino A, et al. Safety and efficacy of combined radiotherapy, immunotherapy and targeted agents in elderly patients: a literature review. Crit Rev Oncol Hematol. 2019;133:163–70. PubMedCrossRef
163.
164.
St Sauver JL, Boyd CM, Grossardt BR, Bobo WV, Finney Rutten LJ, Roger VL, Ebbert JO, Therneau TM, Yawn BP, Rocca WA. Risk of developing multimorbidity across all ages in an historical cohort study: differences by sex and ethnicity. BMJ Open. 2015;5(2):e006413. PubMedPubMedCentralCrossRef
165.
Pignolo RJ, Passos JF, Khosla S, Tchkonia T, Kirkland JL. Reducing senescent cell burden in aging and disease. Trends in molecular medicine. 2020;26(7):630–8. PubMedCrossRefPubMedCentral
166.
Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019;571(7764):183–92. PubMedPubMedCentralCrossRef
167.
McCay CM, Maynard LA, Sperling G, Barnes LL. The Journal of Nutrition. Volume 18 July--December, 1939. Pages 1--13. Retarded growth, life span, ultimate body size and age changes in the albino rat after feeding diets restricted in calories. Nutrit Rev. 1975;33(8):241–43.
168.
Mattison JA, Colman RJ, Beasley TM, Allison DB, Kemnitz JW, Roth GS, Ingram DK, Weindruch R, de Cabo R, Anderson RM. Caloric restriction improves health and survival of rhesus monkeys. Nat Commun. 2017;8:14063. PubMedPubMedCentralCrossRef
169.
Pifferi F, Terrien J, Marchal J, Dal-Pan A, Djelti F, Hardy I, Chahory S, Cordonnier N, Desquilbet L, Hurion M, et al. Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates. Commun Biol. 2018;1:30. PubMedPubMedCentralCrossRef
170.
171.
Kim M-J, Miller CM, Shadrach JL, Wagers AJ, Serwold T. Young, proliferative thymic epithelial cells engraft and function in aging thymuses. J Immunol. 2015;194(10):4784–95. PubMedCrossRef
172.
Sun L, Guo J, Brown R, Amagai T, Zhao Y, Su D-M. Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution. Aging Cell. 2010;9(3):347–57. PubMedCrossRef
173.
Henson SM, Snelgrove R, Hussell T, Wells DJ, Aspinall R. An IL-7 fusion protein that shows increased thymopoietic ability. J Immunol. 2005;175(6):4112–8. PubMedCrossRef
174.
Duggal NA, Pollock RD, Lazarus NR, Harridge S, Lord JM. Major features of immunosenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood. Aging Cell. 2018;17(2):e12750. PubMedCentralCrossRef
175.
Muñoz-Lorente MA, Cano-Martin AC, Blasco MA. Mice with hyper-long telomeres show less metabolic aging and longer lifespans. Nat Commun. 2019;10(1):4723. PubMedPubMedCentralCrossRef
176.
Partridge L, Fuentealba M, Kennedy BK. The quest to slow ageing through drug discovery. Nat Rev Drug Discov. 2020;19(8):513–32. PubMedCrossRef
177.
178.
179.
Strong R, Miller RA, Antebi A, Astle CM, Bogue M, Denzel MS, Fernandez E, Flurkey K, Hamilton KL, Lamming DW, et al. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell. 2016;15(5):872–84. PubMedPubMedCentralCrossRef
180.
Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin M-J, et al. Metformin improves healthspan and lifespan in mice. Nat Commun. 2013;4:2192. PubMedCrossRef
181.
Bannister CA, Holden SE, Jenkins-Jones S, Morgan CL, Halcox JP, Schernthaner G, Mukherjee J, Currie CJ. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab. 2014;16(11):1165–73. PubMedCrossRef
182.
Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW-L, Thomas EL, Kockel L. With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab. 2010;11(6):453–65.
183.
Ha CW, Huh W-K. Rapamycin increases rDNA stability by enhancing association of Sir2 with rDNA in Saccharomyces cerevisiae. Nucleic Acids Res. 2011;39(4):1336–50. PubMedCrossRef
184.
Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460(7253):392–5. PubMedPubMedCentralCrossRef
185.
Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, et al. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol Ser A Biol Sci Med Sci. 2011;66(2):191–201. CrossRef
186.
Kapahi P, Kaeberlein M, Hansen M. Dietary restriction and lifespan: Lessons from invertebrate models. Ageing Res Rev. 2017;39:3–14. PubMedCrossRef
187.
Popovich IG, Anisimov VN, Zabezhinski MA, Semenchenko AV, Tyndyk ML, Yurova MN, Blagosklonny MV. Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin. Cancer Biol Ther. 2014;15(5):586–92. PubMedPubMedCentralCrossRef
188.
Grabiner BC, Nardi V, Birsoy K, Possemato R, Shen K, Sinha S, Jordan A, Beck AH, Sabatini DM. A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity. Cancer Discov. 2014;4(5):554–63. PubMedPubMedCentralCrossRef
189.
Xu J, Pham CG, Albanese SK, Dong Y, Oyama T, Lee C-H, Rodrik-Outmezguine V, Yao Z, Han S, Chen D, et al. Mechanistically distinct cancer-associated mTOR activation clusters predict sensitivity to rapamycin. J Clin Invest. 2016;126(9):3526–40. PubMedPubMedCentralCrossRef
190.
Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schröder S, Adler T, Afonso LC, Aguilar-Pimentel JA, Becker L, Garrett L, et al. Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest. 2013;123(8):3272–91. PubMedPubMedCentralCrossRef
191.
Wilkinson JE, Burmeister L, Brooks SV, Chan C-C, Friedline S, Harrison DE, Hejtmancik JF, Nadon N, Strong R, Wood LK, et al. Rapamycin slows aging in mice. Aging Cell. 2012;11(4):675–82. PubMedCrossRef
192.
Sung JY, Lee KY, Kim J-R, Choi HC. Interaction between mTOR pathway inhibition and autophagy induction attenuates adriamycin-induced vascular smooth muscle cell senescence through decreased expressions of p53/p21/p16. Exp Gerontol. 2018;109:51–8. PubMedCrossRef
193.
Wang R, Sunchu B, Perez VI. Rapamycin and the inhibition of the secretory phenotype. Exp Gerontol. 2017;94:89–92. PubMedCrossRef
194.
Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, Caples K, Bradley L, Beaver LM, Ho E, et al. Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism. Aging Cell. 2017;16(3):564–74. PubMedPubMedCentralCrossRef
195.
196.
Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science (New York, NY). 2015;350(6265):1208–13. CrossRef
197.
Yoshino J, Baur JA, Imai S-I. NAD intermediates: the biology and therapeutic potential of NMN and NR. Cell Metab. 2018;27(3):513–28. PubMedCrossRef
198.
Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol. 2015;11(9):535–46. PubMedCrossRef
199.
Hikosaka K, Yaku K, Okabe K, Nakagawa T. Implications of NAD metabolism in pathophysiology and therapeutics for neurodegenerative diseases. Nutr Neurosci. 2019;1–13.
200.
Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, Brenner C. Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell. 2007;129(3):473–84. PubMedCrossRef
201.
Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cantó C, Mottis A, Jo Y-S, Viswanathan M, Schoonjans K, et al. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154(2):430–41. PubMedPubMedCentralCrossRef
202.
Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, D’Amico D, Ropelle ER, Lutolf MP, Aebersold R, et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science (New York, NY). 2016;352(6292):1436–43. CrossRef
203.
de Picciotto NE, Gano LB, Johnson LC, Martens CR, Sindler AL, Mills KF, Imai S-I, Seals DR. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell. 2016;15(3):522–30. PubMedPubMedCentralCrossRef
204.
Gomes AP, Price NL, Ling AJY, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155(7):1624–38. PubMedPubMedCentralCrossRef
205.
Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 2016;24(6):795–806. PubMedPubMedCentralCrossRef
206.
Stein LR, Imai S-i. Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J. 2014;33(12):1321–40.
207.
Ramsey KM, Mills KF, Satoh A, Imai S-I. Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice. Aging Cell. 2008;7(1):78–88. PubMedCrossRef
208.
Grozio A, Mills KF, Yoshino J, Bruzzone S, Sociali G, Tokizane K, Lei HC, Cunningham R, Sasaki Y, Migaud ME, et al. Slc12a8 is a nicotinamide mononucleotide transporter. Nat Metab. 2019;1(1):47–57. PubMedPubMedCentralCrossRef
209.
210.
211.
Alpert A, Pickman Y, Leipold M, Rosenberg-Hasson Y, Ji X, Gaujoux R, Rabani H, Starosvetsky E, Kveler K, Schaffert S, et al. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat Med. 2019;25(3):487–95. PubMedPubMedCentralCrossRef
212.
Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD(+) and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 2016;17(11):679–90. PubMedPubMedCentralCrossRef
Metadata
Title
Immunosenescence: a key player in cancer development
Authors
Jingyao Lian
Ying Yue
Weina Yu
Yi Zhang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2020
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-020-00986-z

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