The population of childhood cancer survivors (CCS) has grown rapidly in recent decades. Although cured of their original malignancy, these individuals are at increased risk of serious late effects, including age-associated complications. An impaired immune system has been linked to the emergence of these conditions in the elderly and CCS, likely due to senescent immune cell phenotypes accompanied by low-grade inflammation, which in the elderly is known as "inflammaging." Whether these observations in the elderly and CCS are underpinned by similar mechanisms is unclear. If so, existing knowledge on immunosenescent phenotypes and inflammaging might potentially serve to benefit CCS. We summarize recent findings on the immune changes in CCS and the elderly, and highlight the similarities and identify areas for future research. Improving our understanding of the underlying mechanisms and immunosenescent markers of accelerated immune aging might help us to identify individuals at increased risk of serious health complications.

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Pediatric Oncology University Hospital Brno Brno Czech Republic

Institute of Hematology and Blood Transfusion Prague Czech Republic

International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic

Zobrazit více v PubMed

Agrawal A., Agrawal S., Gupta S. (2017). Role of Dendritic Cells in Inflammation and Loss of Tolerance in the Elderly. Front. Immunol. 8, 896. 10.3389/fimmu.2017.00896 PubMed DOI PMC

Agrawal A., Agrawal S., Cao J.-N., Su H., Osann K., Gupta S. (2007). Altered Innate Immune Functioning of Dendritic Cells in Elderly Humans: A Role of Phosphoinositide 3-Kinase-Signaling Pathway. J. Immunol. 178 (11), 6912–6922. 10.4049/jimmunol.178.11.6912 PubMed DOI

Agrawal S., Ganguly S., Tran A., Sundaram P., Agrawal A. (2016). Retinoic Acid Treated Human Dendritic Cells Induce T Regulatory Cells via the Expression of CD141 and GARP Which Is Impaired with Age. Aging 8 (6), 1223–1235. 10.18632/aging.100973 PubMed DOI PMC

Aiello A., Farzaneh F., Candore G., Caruso C., Davinelli S., Gambino C. M., et al. (2019). Immunosenescence and its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention. Front. Immunol. 10, 2247. 10.3389/fimmu.2019.02247 PubMed DOI PMC

Akbar A. N., Henson S. M., Lanna A. (2016). Senescence of T Lymphocytes: Implications for Enhancing Human Immunity. Trends Immunol. 37 (12), 866–876. 10.1016/j.it.2016.09.002 PubMed DOI

Alessio N., Aprile D., Squillaro T., Di Bernardo G., Finicelli M., Melone M. A., et al. (2019). The Senescence-Associated Secretory Phenotype (SASP) from Mesenchymal Stromal Cells Impairs Growth of Immortalized Prostate Cells but has No Effect on Metastatic Prostatic Cancer Cells. Aging 11 (15), 5817–5828. 10.18632/aging.102172 PubMed DOI PMC

Allsopp R. C., Cheshier S., Weissman I. L. (2001). Telomere Shortening Accompanies Increased Cell Cycle Activity during Serial Transplantation of Hematopoietic Stem Cells. J. Exp. Med. 193 (8), 917–924. 10.1084/jem.193.8.917 PubMed DOI PMC

Angelovich T. A., Shi M. D. Y., Zhou J., Maisa A., Hearps A. C., Jaworowski A. (2016). Ex Vivo foam Cell Formation is Enhanced in Monocytes from Older Individuals by Both Extrinsic and Intrinsic Mechanisms. Exp. Gerontol. 80, 17–26. 10.1016/j.exger.2016.04.006 PubMed DOI

Ariffin H., Azanan M. S., Abd Ghafar S. S., Oh L., Lau K. H., Thirunavakarasu T., et al. (2017). Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia Show Evidence of Chronic Inflammation and Cellular Aging. Cancer 123 (21), 4207–4214. 10.1002/cncr.30857 PubMed DOI

Armstrong G. T., Kawashima T., Leisenring W., Stratton K., Stovall M., Hudson M. M., et al. (2014). Aging and Risk of Severe, Disabling, Life-Threatening, and Fatal Events in the Childhood Cancer Survivor Study. J. Clin. Oncol. 32 (12), 1218–1227. 10.1200/jco.2013.51.1055 PubMed DOI PMC

Armstrong G. T., Oeffinger K. C., Chen Y., Kawashima T., Yasui Y., Leisenring W., et al. (2013). Modifiable Risk Factors and Major Cardiac Events Among Adult Survivors of Childhood Cancer. J. Clin. Oncol. 31 (29), 3673–3680. 10.1200/jco.2013.49.3205 PubMed DOI PMC

Armstrong G. T., Stovall M., Robison L. L. (2010). Long-term Effects of Radiation Exposure Among Adult Survivors of Childhood Cancer: Results from the Childhood Cancer Survivor Study. Radiat. Res. 174 (6), 840–850. 10.1667/rr1903.1 PubMed DOI PMC

Arnold C. R., Pritz T., Brunner S., Knabb C., Salvenmoser W., Holzwarth B., et al. (2014). T Cell Receptor-Mediated Activation Is a Potent Inducer of Macroautophagy in Human CD8+CD28+ T Cells but Not in CD8+CD28− T Cells. Exp. Gerontol. 54, 75–83. 10.1016/j.exger.2014.01.018 PubMed DOI

Arroyo E., Wells A. J., Gordon J. A., 3rd, Varanoske A. N., Gepner Y., Coker N. A., et al. (2017). Tumor Necrosis Factor-Alpha and Soluble TNF-Alpha Receptor Responses in Young vs. Middle-Aged Males Following Eccentric Exercise. Exp. Gerontol. 100, 28–35. 10.1016/j.exger.2017.10.012 PubMed DOI

Azanan M. S., Abdullah N. K., Chua L. L., Lum S. H., Abdul Ghafar S. S., Kamarulzaman A., et al. (2016). Immunity in Young Adult Survivors of Childhood Leukemia is Similar to the Elderly Rather Than Age-Matched Controls: Role of Cytomegalovirus. Eur. J. Immunol. 46 (7), 1715–1726. 10.1002/eji.201646356 PubMed DOI

Baerlocher G. M., Rovó A., Müller A., Matthey S., Stern M., Halter J., et al. (2009). Cellular Senescence of white Blood Cells in Very Long-Term Survivors After Allogeneic Hematopoietic Stem Cell Transplantation: The Role of Chronic Graft-Versus-Host Disease and Female Donor Sex. Blood 114 (1), 219–222. 10.1182/blood-2009-03-209833 PubMed DOI

Bartlett D. B., Fox O., McNulty C. L., Greenwood H. L., Murphy L., Sapey E., et al. (2016). Habitual Physical Activity Is Associated with the Maintenance of Neutrophil Migratory Dynamics in Healthy Older Adults. Brain Behav. Immun. 56, 12–20. 10.1016/j.bbi.2016.02.024 PubMed DOI PMC

Bates J. E., Howell R. M., Liu Q., Yasui Y., Mulrooney D. A., Dhakal S., et al. (2019). Therapy-Related Cardiac Risk in Childhood Cancer Survivors: An Analysis of the Childhood Cancer Survivor Study. J. Clin. Oncol. 37 (13), 1090–1101. 10.1200/jco.18.01764 PubMed DOI PMC

Beerman I., Bock C., Garrison B. S., Smith Z. D., Gu H., Meissner A., et al. (2013). Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging. Cell Stem Cell 12 (4), 413–425. 10.1016/j.stem.2013.01.017 PubMed DOI

Beharka A. A., Meydani M., Wu D., Leka L. S., Meydani A., Meydani S. N. (2001). Interleukin-6 Production Does Not Increase with Age. J. Gerontol. Ser. A: Biol. Sci. Med. Sci. 56 (2), B81–B88. 10.1093/gerona/56.2.b81 PubMed DOI

Bell J. T., Tsai P. C., Yang T. P., Pidsley R., Nisbet J., Glass D., et al. (2012). Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population. PLoS Genet. 8 (4), e1002629. 10.1371/journal.pgen.1002629 PubMed DOI PMC

Bhakta N., Liu Q., Ness K. K., Baassiri M., Eissa H., Yeo F., et al. (2017). The Cumulative burden of Surviving Childhood Cancer: an Initial Report from the St Jude Lifetime Cohort Study (SJLIFE). Lancet 390 (10112), 2569–2582. 10.1016/s0140-6736(17)31610-0 PubMed DOI PMC

Bischoff C., Graakjaer J., Petersen H. C., Hjelmborg J. v. B., Vaupel J. W., Bohr V., et al. (2005). The Heritability of Telomere Length Among the Elderly and Oldest-Old. Twin Res. Hum. Genet. 8 (5), 433–439. 10.1375/twin.8.5.433 PubMed DOI

Blanco E., Pérez-Andrés M., Arriba-Méndez S., Contreras-Sanfeliciano T., Criado I., Pelak O., et al. (2018). Age-Associated Distribution of Normal B-Cell and Plasma Cell Subsets in Peripheral Blood. J. Allergy Clin. Immunol. 141 (6), 2208–2219. 10.1016/j.jaci.2018.02.017 PubMed DOI

Bollati V., Schwartz J., Wright R., Litonjua A., Tarantini L., Suh H., et al. (2009). Decline in Genomic DNA Methylation through Aging in a Cohort of Elderly Subjects. Mech. Ageing Dev. 130 (4), 234–239. 10.1016/j.mad.2008.12.003 PubMed DOI PMC

Boucher N., Dufeu-Duchesne T., Vicaut E., Farge D., Effros R. B., Schächter F. (1998). CD28 Expression in T Cell Aging and Human Longevity. Exp. Gerontol. 33 (3), 267–282. 10.1016/s0531-5565(97)00132-0 PubMed DOI

Bredenkamp N., Nowell C. S., Blackburn C. C. (2014b). Regeneration of the Aged Thymus by a Single Transcription Factor. Development 141 (8), 1627–1637. 10.1242/dev.103614 PubMed DOI PMC

Bredenkamp N., Ulyanchenko S., O’Neill K. E., Manley N. R., Vaidya H. J., Blackburn C. C. (2014a). An Organized and Functional Thymus Generated from FOXN1-Reprogrammed Fibroblasts. Nat. Cell Biol 16 (9), 902–908. 10.1038/ncb3023 PubMed DOI PMC

Brenchley J. M., Karandikar N. J., Betts M. R., Ambrozak D. R., Hill B. J., Crotty L. E., et al. (2003). Expression of CD57 Defines Replicative Senescence and Antigen-Induced Apoptotic Death of CD8+ T Cells. Blood 101 (7), 2711–2720. 10.1182/blood-2002-07-2103 PubMed DOI

Brignardello E., Felicetti F., Castiglione A., Chiabotto P., Corrias A., Fagioli F., et al. (2013). Endocrine Health Conditions in Adult Survivors of Childhood Cancer: the Need for Specialized Adult-Focused Follow-Up Clinics. Eur. J. Endocrinol. 168 (3), 465–472. 10.1530/eje-12-1043 PubMed DOI

Brubaker A. L., Rendon J. L., Ramirez L., Choudhry M. A., Kovacs E. J. (2013). Reduced Neutrophil Chemotaxis and Infiltration Contributes to Delayed Resolution of Cutaneous Wound Infection with Advanced Age. J. Immunol. 190 (4), 1746–1757. 10.4049/jimmunol.1201213 PubMed DOI PMC

Bruni E., Cazzetta V., Donadon M., Cimino M., Torzilli G., Spata G., et al. (2019). Chemotherapy Accelerates Immune-Senescence and Functional Impairments of Vdelta2(pos) T Cells in Elderly Patients Affected by Liver Metastatic Colorectal Cancer. J. Immunother. Cancer 7 (1), 347. 10.1186/s40425-019-0825-4 PubMed DOI PMC

Brusnahan S. K., McGuire T. R., Jackson J. D., Lane J. T., Garvin K. L., O'Kane B. J., et al. (2010). Human Blood and Marrow Side Population Stem Cell and Stro-1 Positive Bone Marrow Stromal Cell Numbers Decline with Age, With an Increase in Quality of Surviving Stem Cells: Correlation with Cytokines. Mech. Ageing Dev. 131 (11-12), 718–722. 10.1016/j.mad.2010.10.002 PubMed DOI PMC

Bruunsgaard H., Andersen-Ranberg K., Jeune B., Pedersen A. N., Skinhoj P., Pedersen B. K. (1999). A High Plasma Concentration of TNF- Is Associated With Dementia in Centenarians. J. Gerontol. Ser. A: Biol. Sci. Med. Sci. 54 (7), M357–M364. 10.1093/gerona/54.7.m357 PubMed DOI

Bruunsgaard H., Skinhøj P., Pedersen A. N., Schroll M., Pedersen B. K. (2000). Ageing, Tumour Necrosis Factor-Alpha (TNF-α) and Atherosclerosis. Clin. Exp. Immunol. 121 (2), 255–260. 10.1046/j.1365-2249.2000.01281.x PubMed DOI PMC

Burnham A. J., Daley-Bauer L. P., Horwitz E. M. (2020). Mesenchymal Stromal Cells in Hematopoietic Cell Transplantation. Blood Adv. 4 (22), 5877–5887. 10.1182/bloodadvances.2020002646 PubMed DOI PMC

Butcher S. K., Chahal H., Nayak L., Sinclair A., Henriquez N. V., Sapey E., et al. (2001). Senescence in Innate Immune Responses: Reduced Neutrophil Phagocytic Capacity and CD16 Expression in Elderly Humans. J. Leukoc. Biol. 70 (6), 881–886. 10.1189/jlb.70.6.881 PubMed DOI

Callender L. A., Carroll E. C., Beal R. W. J., Chambers E. S., Nourshargh S., Akbar A. N., et al. (2018). Human CD8(+) EMRA T Cells Display a Senescence-Associated Secretory Phenotype Regulated by P38 MAPK. Aging Cell 17 (1), e12675. 10.1111/acel.12675 PubMed DOI PMC

Cartier A., Côté M., Lemieux I., Pérusse L., Tremblay A., Bouchard C., et al. (2009). Age-Related Differences in Inflammatory Markers in Men: Contribution of Visceral Adiposity. Metabolism 58 (10), 1452–1458. 10.1016/j.metabol.2009.04.025 PubMed DOI

Casella G., Munk R., Kim K. M., Piao Y., De S., Abdelmohsen K., et al. (2019). Transcriptome Signature of Cellular Senescence. Nucleic Acids Res. 47 (14), 7294–7305. 10.1093/nar/gkz555 PubMed DOI PMC

Castagna L., Bramanti S., Furst S., Giordano L., Sarina B., Crocchiolo R., et al. (2016). Tacrolimus Compared With Cyclosporine A After Haploidentical T-Cell Replete Transplantation With Post-Infusion Cyclophosphamide. Bone Marrow Transpl. 51 (3), 462–465. 10.1038/bmt.2015.289 PubMed DOI

Castañeda-Delgado J. E., Frausto-Lujan I., González-Curiel I., Montoya-Rosales A., Serrano C. J., Torres-Juarez F., et al. (2017). Differences in Cytokine Production during Aging and its Relationship with Antimicrobial Peptides Production. Immunol. Invest. 46 (1), 48–58. 10.1080/08820139.2016.1212873 PubMed DOI

Cepelova M., Kruseova J., Luks A., Capek V., Cepela P., Potockova J., et al. (2019). Accelerated Atherosclerosis, Hyperlipoproteinemia and Insulin Resistance in Long-Term Survivors of Hodgkin Lymphoma During Childhood and Adolescence. Neoplasma 66 (6), 978–987. 10.4149/neo_2019_190115n45 PubMed DOI

Chen G., Yung R. (2019). Meta‐Inflammaging at the Crossroad of Geroscience. Aging Med. 2 (3), 157–161. 10.1002/agm2.12078 PubMed DOI PMC

Chidrawar S. M., Khan N., Chan Y. L. T., Nayak L., Moss P. A. (2006). Ageing is Associated With a Decline in Peripheral Blood CD56bright NK Cells. Immun. Ageing 3, 10. 10.1186/1742-4933-3-10 PubMed DOI PMC

Childs B. G., Gluscevic M., Baker D. J., Laberge R.-M., Marquess D., Dananberg J., et al. (2017). Senescent Cells: An Emerging Target for Diseases of Ageing. Nat. Rev. Drug Discov. 16 (10), 718–735. 10.1038/nrd.2017.116 PubMed DOI PMC

Choi D. K., Strzepka J. T., Hunt S. R., Tannenbaum V. L., Jang I. E. (2020). Vaccination in Pediatric Cancer Survivors: Vaccination Rates, Immune Status, and Knowledge Regarding Compliance. Pediatr. Blood Cancer 67 (10), e28565. 10.1002/pbc.28565 PubMed DOI

Chow E. J., Baker K. S., Lee S. J., Flowers M. E. D., Cushing-Haugen K. L., Inamoto Y., et al. (2014). Influence of Conventional Cardiovascular Risk Factors and Lifestyle Characteristics on Cardiovascular Disease after Hematopoietic Cell Transplantation. J. Clin. Oncol. 32 (3), 191–198. 10.1200/jco.2013.52.6582 PubMed DOI PMC

Chow E. J., Simmons J. H., Roth C. L., Baker K. S., Hoffmeister P. A., Sanders J. E., et al. (2010). Increased Cardiometabolic Traits in Pediatric Survivors of Acute Lymphoblastic Leukemia Treated With Total Body Irradiation. Biol. Blood Marrow Transplant. 16 (12), 1674–1681. 10.1016/j.bbmt.2010.05.016 PubMed DOI PMC

Christensen B. C., Houseman E. A., Marsit C. J., Zheng S., Wrensch M. R., Wiemels J. L., et al. (2009). Aging and Environmental Exposures Alter Tissue-specific DNA Methylation Dependent Upon CpG Island Context. PLoS Genet. 5 (8), e1000602. 10.1371/journal.pgen.1000602 PubMed DOI PMC

Chua L. L., Rajasuriar R., Azanan M. S., Abdullah N. K., Tang M. S., Lee S. C., et al. (2017). Reduced Microbial Diversity in Adult Survivors of Childhood Acute Lymphoblastic Leukemia and Microbial Associations With Increased Immune Activation. Microbiome 5 (1), 35. 10.1186/s40168-017-0250-1 PubMed DOI PMC

Ciernikova S., Mego M., Semanova M., Wachsmannova L., Adamcikova Z., Stevurkova V., et al. (2017). Probiotic Survey in Cancer Patients Treated in the Outpatient Department in a Comprehensive Cancer Center. Integr. Cancer Ther. 16 (2), 188–195. 10.1177/1534735416643828 PubMed DOI PMC

Clemens E., van der Kooi A. L. F., Broer L., van Dulmen-den Broeder E., Visscher H., Kremer L., et al. (2018). The Influence of Genetic Variation on Late Toxicities in Childhood Cancer Survivors: A Review. Crit. Rev. Oncol. Hematol. 126, 154–167. 10.1016/j.critrevonc.2018.04.001 PubMed DOI

Cohen H. Y., Miller C., Bitterman K. J., Wall N. R., Hekking B., Kessler B., et al. (2004). Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase. Science 305 (5682), 390–392. 10.1126/science.1099196 PubMed DOI

Collerton J., Martin-Ruiz C., Davies K., Hilkens C. M., Isaacs J., Kolenda C., et al. (2012). Frailty and the Role of Inflammation, Immunosenescence and Cellular Ageing in the Very Old: Cross-Sectional Findings from the Newcastle 85+ Study. Mech. Ageing Dev. 133 (6), 456–466. 10.1016/j.mad.2012.05.005 PubMed DOI

Cupit-Link M. C., Kirkland J. L., Ness K. K., Armstrong G. T., Tchkonia T., LeBrasseur N. K., et al. (2017). Biology of Premature Ageing in Survivors of Cancer. ESMO Open 2 (5), e000250. 10.1136/esmoopen-2017-000250 PubMed DOI PMC

Daniel S., Nylander V., Ingerslev L. R., Zhong L., Fabre O., Clifford B., et al. (2018). T Cell Epigenetic Remodeling and Accelerated Epigenetic Aging Are Linked to Long-Term Immune Alterations in Childhood Cancer Survivors. Clin. Epigenetics 10 (1), 138. 10.1186/s13148-018-0561-5 PubMed DOI PMC

Di Mitri D., Azevedo R. I., Henson S. M., Libri V., Riddell N. E., Macaulay R., et al. (2011). Reversible Senescence in Human CD4+CD45RA+CD27− Memory T Cells. J. Immunol. 187 (5), 2093–2100. 10.4049/jimmunol.1100978 PubMed DOI

Dimri G. P., Lee X., Basile G., Acosta M., Scott G., Roskelley C., et al. (1995). A Biomarker that Identifies Senescent Human Cells in Culture and in Aging Skin In Vivo . Proc. Natl. Acad. Sci. 92 (20), 9363–9367. 10.1073/pnas.92.20.9363 PubMed DOI PMC

Donato A. J., Black A. D., Jablonski K. L., Gano L. B., Seals D. R. (2008). Aging is Associated With Greater Nuclear NFκB, Reduced IκBα, and Increased Expression of Proinflammatory Cytokines in Vascular Endothelial Cells of Healthy Humans. Aging Cell 7 (6), 805–812. 10.1111/j.1474-9726.2008.00438.x PubMed DOI PMC

Duggal N. A., Pollock R. D., Lazarus N. R., Harridge S., Lord J. M. (2018). Major Features of Immunesenescence, Including Reduced Thymic Output, Are Ameliorated by High Levels of Physical Activity in Adulthood. Aging Cell 17 (2). 10.1111/acel.12750 PubMed DOI PMC

Duggal N. A. (2018). Reversing the Immune Ageing Clock: Lifestyle Modifications and Pharmacological Interventions. Biogerontology 19 (6), 481–496. 10.1007/s10522-018-9771-7 PubMed DOI PMC

Edgar A. B., Duffin K., Borthwick S., Marciniak-Stepak P., Wallace W. H. (2013). Can Intensity of Long-Term Follow-Up for Survivors of Childhood and Teenage Cancer be Determined by Therapy-Based Risk Stratification? BMJ Open 3 (8). 10.1136/bmjopen-2012-002451 PubMed DOI PMC

Effinger K. E., Stratton K. L., Fisher P. G., Ness K. K., Krull K. R., Oeffinger K. C., et al. (2019). Long-Term Health and Social Function in Adult Survivors of Paediatric Astrocytoma: A Report from the Childhood Cancer Survivor Study. Eur. J. Cancer 106, 171–180. 10.1016/j.ejca.2018.10.016 PubMed DOI PMC

Effros R. B., Boucher N., Porter V., Zhu X., Spaulding C., Walford R. L., et al. (1994). Decline in CD28+ T Cells in Centenarians and in Long-Term T Cell Cultures: a Possible Cause for Both In Vivo and In Vitro Immunosenescence. Exp. Gerontol. 29 (6), 601–609. 10.1016/0531-5565(94)90073-6 PubMed DOI

Erskine R. M., Tomlinson D. J., Morse C. I., Winwood K., Hampson P., Lord J. M., et al. (2017). The Individual and Combined Effects of Obesity- and Ageing-Induced Systemic Inflammation on Human Skeletal Muscle Properties. Int. J. Obes. 41 (1), 102–111. 10.1038/ijo.2016.151 PubMed DOI PMC

Fagnoni F. F., Vescovini R., Mazzola M., Bologna G., Nigro E., Lavagetto G., et al. (1996). Expansion of Cytotoxic CD8 + CD28 − T Cells in Healthy Ageing People, Including Centenarians. Immunology 88 (4), 501–507. 10.1046/j.1365-2567.1996.d01-689.x PubMed DOI PMC

Fali T., Fabre-Mersseman V., Yamamoto T., Bayard C., Papagno L., Fastenackels S., et al. (2018). Elderly Human Hematopoietic Progenitor Cells Express Cellular Senescence Markers and are More Susceptible to Pyroptosis. JCI Insight 3 (13), e95319. 10.1172/jci.insight.95319 PubMed DOI PMC

Farrell T. L., McGuire T. R., Bilek L. D., Brusnahan S. K., Jackson J. D., Lane J. T., et al. (2014). Changes in the Frequencies of Human Hematopoietic Stem and Progenitor Cells With Age and Site. Exp. Hematol. 42 (2), 146–154. 10.1016/j.exphem.2013.11.003 PubMed DOI PMC

Felicetti F., Manicone R., Corrias A., Manieri C., Biasin E., Bini I., et al. (2011). Endocrine Late Effects After Total Body Irradiation in Patients Who Received Hematopoietic Cell Transplantation During Childhood: A Retrospective Study From a Single Institution. J. Cancer Res. Clin. Oncol. 137 (9), 1343–1348. 10.1007/s00432-011-1004-2 PubMed DOI PMC

Ferrucci L., Corsi A., Lauretani F., Bandinelli S., Bartali B., Taub D. D., et al. (2005). The Origins of Age-Related Proinflammatory State. Blood 105 (6), 2294–2299. 10.1182/blood-2004-07-2599 PubMed DOI PMC

Fischer C. P., Berntsen A., Perstrup L. B., Eskildsen P., Pedersen B. K. (2007). Plasma Levels of Interleukin-6 and C-Reactive Protein Are Associated With Physical Inactivity Independent of Obesity. Scand. J. Med. Sci. Sports 17 (5), 580–587. 10.1111/j.1600-0838.2006.00602.x PubMed DOI

Forrester S. J., Kikuchi D. S., Hernandes M. S., Xu Q., Griendling K. K. (2018). Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circ. Res. 122 (6), 877–902. 10.1161/circresaha.117.311401 PubMed DOI PMC

Forsey R. J., Thompson J. M., Ernerudh J., Hurst T. L., Strindhall J., Johansson B., et al. (2003). Plasma Cytokine Profiles in Elderly Humans. Mech. Ageing Dev. 124 (4), 487–493. 10.1016/s0047-6374(03)00025-3 PubMed DOI

Fowler H., Belot A., Ellis L., Maringe C., Luque-Fernandez M. A., Njagi E. N., et al. (2020). Comorbidity Prevalence Among Cancer Patients: A Population-Based Cohort Study of Four Cancers. BMC Cancer 20 (1), 2. 10.1186/s12885-019-6472-9 PubMed DOI PMC

Franceschi C., Bonafè M., Valensin S., Olivieri F., De Luca M., Ottaviani E., et al. (2000a). Inflamm-aging. An Evolutionary Perspective on Immunosenescence. Ann. N. Y Acad. Sci. 908, 244–254. 10.1111/j.1749-6632.2000.tb06651.x PubMed DOI

Franceschi C., Bonafè M., Valensin S. (2000b). Human Immunosenescence: The Prevailing of Innate Immunity, the Failing of Clonotypic Immunity, and the Filling of Immunological Space. Vaccine 18 (16), 1717–1720. 10.1016/s0264-410x(99)00513-7 PubMed DOI

Franceschi C., Garagnani P., Vitale G., Capri M., Salvioli S. (2017). Inflammaging and 'Garb-Aging'. Trends Endocrinol. Metab. 28 (3), 199–212. 10.1016/j.tem.2016.09.005 PubMed DOI

Franco S., Ozkaynak M. F., Sandoval C., Tugal O., Jayabose S., Engelhardt M., et al. (2003). Telomere Dynamics in Childhood Leukemia and Solid Tumors: A Follow-Up Study. Leukemia 17 (2), 401–410. 10.1038/sj.leu.2402815 PubMed DOI

Frasca D., Diaz A., Romero M., Blomberg B. B. (2017). Human Peripheral Late/Exhausted Memory B Cells Express a Senescent-Associated Secretory Phenotype and Preferentially Utilize Metabolic Signaling Pathways. Exp. Gerontol. 87 (Pt A), 113–120. 10.1016/j.exger.2016.12.001 PubMed DOI

Frasca D., Diaz A., Romero M., D'Eramo F., Blomberg B. B. (2017). Aging Effects on T-Bet Expression in Human B Cell Subsets. Cell Immunol. 321, 68–73. 10.1016/j.cellimm.2017.04.007 PubMed DOI

Frasca D., Ferracci F., Diaz A., Romero M., Lechner S., Blomberg B. B. (2016). Obesity Decreases B Cell Responses in Young and Elderly Individuals. Obesity 24 (3), 615–625. 10.1002/oby.21383 PubMed DOI PMC

Fried L. P., Tangen C. M., Walston J., Newman A. B., Hirsch C., Gottdiener J., et al. (2001). Frailty in Older Adults: Evidence for a Phenotype. J. Gerontol. Ser. A: Biol. Sci. Med. Sci. 56 (3), M146–M157. 10.1093/gerona/56.3.m146 PubMed DOI

Frobisher C., Glaser A., Glaser A., Levitt G. A., Cutter D. J., Winter D. L., et al. (2017). Risk Stratification of Childhood Cancer Survivors Necessary for Evidence-Based Clinical Long-Term Follow-Up. Br. J. Cancer 117 (11), 1723–1731. 10.1038/bjc.2017.347 PubMed DOI PMC

Fucikova J., Moserova I., Urbanova L., Bezu L., Kepp O., Cremer I., et al. (2015). Prognostic and Predictive Value of DAMPs and DAMP-Associated Processes in Cancer. Front. Immunol. 6, 402. 10.3389/fimmu.2015.00402 PubMed DOI PMC

Fülöp T., Larbi A., Witkowski J. M. (2019). Human Inflammaging. Gerontology 65 (5), 495–504. 10.1159/000497375 PubMed DOI

Fulop T., Larbi A., Witkowski J. M., Kotb R., Hirokawa K., Pawelec G. (2013). Immunosenescence and Cancer. Crit. Rev. Oncog 18 (6), 489–513. 10.1615/critrevoncog.2013010597 PubMed DOI

Fulop T., Witkowski J. M., Le Page A., Fortin C., Pawelec G., Larbi A. (2017). Intracellular Signalling Pathways: Targets to Reverse Immunosenescence. Clin. Exp. Immunol. 187 (1), 35–43. 10.1111/cei.12836 PubMed DOI PMC

Gallicchio L., Kalesan B., Hoffman S. C., Helzlsouer K. J. (2008). Non-cancer Adverse Health Conditions and Perceived Health and Function Among Cancer Survivors Participating in a Community-Based Cohort Study in Washington County, Maryland. J. Cancer Surviv. 2 (1), 12–19. 10.1007/s11764-008-0046-1 PubMed DOI

Gangemi S., Basile G., Monti D., Merendino R. A., Pasquale G. D., Bisignano U., et al. (2005). Age-related Modifications in Circulating IL-15 Levels in Humans. Mediators Inflamm. 2005 (4), 245–247. 10.1155/mi.2005.245 PubMed DOI PMC

Garbe K., Bratke K., Wagner S., Virchow J. C., Lommatzsch M. (2012). Plasmacytoid Dendritic Cells and Their Toll-Like Receptor 9 Expression Selectively Decrease With Age. Hum. Immunol. 73 (5), 493–497. 10.1016/j.humimm.2012.02.007 PubMed DOI

Gardner E. M. (2005). Caloric Restriction Decreases Survival of Aged Mice in Response to Primary Influenza Infection. J. Gerontol. Ser. A: Biol. Sci. Med. Sci. 60 (6), 688–694. 10.1093/gerona/60.6.688 PubMed DOI

Gatta G., Botta L., Rossi S., Aareleid T., Bielska-Lasota M., Clavel J., et al. (2014). Childhood Cancer Survival in Europe 1999-2007: Results of EUROCARE-5-A Population-Based Study. Lancet Oncol. 15 (1), 35–47. 10.1016/s1470-2045(13)70548-5 PubMed DOI

Gavazzi G., Mallaret M. R., Couturier P., Iffenecker A., Franco A. (2002). Bloodstream Infection: Differences Between Young‐Old, Old, and Old‐Old Patients. J. Am. Geriatr. Soc. 50 (10), 1667–1673. 10.1046/j.1532-5415.2002.50458.x PubMed DOI

Geenen M. M., Cardous-Ubbink M. C., Kremer L. C. M., van den Bos C., van der Pal H. J. H., Heinen R. C., et al. (2007). Medical Assessment of Adverse Health Outcomes in Long-Term Survivors of Childhood Cancer. JAMA 297 (24), 2705–2715. 10.1001/jama.297.24.2705 PubMed DOI

Genovese G., Kähler A. K., Handsaker R. E., Lindberg J., Rose S. A., Bakhoum S. F., et al. (2014). Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence. N. Engl. J. Med. 371 (26), 2477–2487. 10.1056/nejmoa1409405 PubMed DOI PMC

Goldberg E. L., Romero‐Aleshire M. J., Renkema K. R., Ventevogel M. S., Chew W. M., Uhrlaub J. L., et al. (2015). Lifespan‐Extending Caloric Restriction or mTOR Inhibition Impair Adaptive Immunity of Old Mice by Distinct Mechanisms. Aging cell 14 (1), 130–138. 10.1111/acel.12280 PubMed DOI PMC

Goossen G. M., Kremer L. C., van de Wetering M. D. (2013). Influenza Vaccination in Children Being Treated with Chemotherapy for Cancer. Cochrane Database Syst. Rev. 2013 (8), CD006484. 10.1002/14651858.CD006484.pub2 PubMed DOI PMC

Gramatges M. M., Liu Q., Yasui Y., Okcu M. F., Neglia J. P., Strong L. C., et al. (2014). Telomere Content and Risk of Second Malignant Neoplasm in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. Clin. Cancer Res. 20 (4), 904–911. 10.1158/1078-0432.ccr-13-2076 PubMed DOI PMC

Granot T., Senda T., Carpenter D. J., Matsuoka N., Weiner J., Gordon C. L., et al. (2017). Dendritic Cells Display Subset and Tissue-Specific Maturation Dynamics Over Human Life. Immunity 46 (3), 504–515. 10.1016/j.immuni.2017.02.019 PubMed DOI PMC

Guida J. L., Agurs-Collins T., Ahles T. A., Campisi J., Dale W., Demark-Wahnefried W., et al. (2021). Strategies to Prevent or Remediate Cancer and Treatment-Related Aging. J. Natl. Cancer Inst. 113 (2), 112–122. 10.1093/jnci/djaa060 PubMed DOI PMC

Haapanen M. J., Perälä M.-M., Salonen M. K., Guzzardi M. A., Iozzo P., Kajantie E., et al. (2018). Telomere Length and Frailty: The Helsinki Birth Cohort Study. J. Am. Med. Dir. Assoc. 19 (8), 658–662. 10.1016/j.jamda.2018.05.011 PubMed DOI

Halper B., Hofmann M., Oesen S., Franzke B., Stuparits P., Vidotto C., et al. (2015). Influence of Age and Physical Fitness on miRNA-21, TGF-β and its Receptors in Leukocytes of Healthy Women. Exerc. Immunol. Rev. 21, 154–163. PubMed

Han J. H., Harmoney K. M., Dokmeci E., Torrez J., Chavez C. M., Cordova de Ortega L., et al. (2018). Dynamic Re-immunization of Off-Treatment Childhood Cancer Survivors: An Implementation Feasibility Study. PLoS One 13 (2), e0191804. 10.1371/journal.pone.0191804 PubMed DOI PMC

Han J. W., Kwon S. Y., Won S. C., Shin Y. J., Ko J. H., Lyu C. J. (2009). Comprehensive Clinical Follow-Up of Late Effects in Childhood Cancer Survivors Shows the Need for Early and Well-Timed Intervention. Ann. Oncol. 20 (7), 1170–1177. 10.1093/annonc/mdn778 PubMed DOI

Hao Y., O’Neill P., Naradikian M. S., Scholz J. L., Cancro M. P. (2011). A B-Cell Subset Uniquely Responsive to Innate Stimuli Accumulates in Aged Mice. Blood 118 (5), 1294–1304. 10.1182/blood-2011-01-330530 PubMed DOI PMC

Harrison D. E., Strong R., Sharp Z. D., Nelson J. F., Astle C. M., Flurkey K., et al. (2009). Rapamycin Fed Late in Life Extends Lifespan in Genetically Heterogeneous Mice. Nature 460 (7253), 392–395. 10.1038/nature08221 PubMed DOI PMC

Haycock P. C., Heydon E. E., Kaptoge S., Butterworth A. S., Thompson A., Willeit P. (2014). Leucocyte Telomere Length and Risk of Cardiovascular Disease: Systematic Review and Meta-Analysis. BMJ 349, g4227. 10.1136/bmj.g4227 PubMed DOI PMC

Hazeldine J., Harris P., Chapple I. L., Grant M., Greenwood H., Livesey A., et al. (2014). Impaired Neutrophil Extracellular Trap Formation: a Novel Defect in the Innate Immune System of Aged Individuals. Aging Cell 13 (4), 690–698. 10.1111/acel.12222 PubMed DOI PMC

Hearps A. C., Martin G. E., Angelovich T. A., Cheng W.-J., Maisa A., Landay A. L., et al. (2012). Aging is Associated With Chronic Innate Immune Activation and Dysregulation of Monocyte Phenotype and Function. Aging Cell 11 (5), 867–875. 10.1111/j.1474-9726.2012.00851.x PubMed DOI

Hendriks J., Gravestein L. A., Tesselaar K., van Lier R. A. W., Schumacher T. N. M., Borst J. (2000). CD27 Is Required for Generation and Long-Term Maintenance of T Cell Immunity. Nat. Immunol. 1 (5), 433–440. 10.1038/80877 PubMed DOI

Henson S. M., Snelgrove R., Hussell T., Wells D. J., Aspinall R. (2005). An IL-7 Fusion Protein that Shows Increased Thymopoietic Ability. J. Immunol. 175 (6), 4112–4118. 10.4049/jimmunol.175.6.4112 PubMed DOI

Herranz N., Gil J. (2018). Mechanisms and Functions of Cellular Senescence. J. Clin. Invest. 128 (4), 1238–1246. 10.1172/jci95148 PubMed DOI PMC

Hooten N. N., Fitzpatrick M., Wood W. H., 3rd, De S., Ejiogu N., Zhang Y., et al. (2013). Age-Related Changes in microRNA Levels in Serum. Aging 5 (10), 725–740. 10.18632/aging.100603 PubMed DOI PMC

Hortova-Kohoutkova M., Laznickova P., Fric J. (2021). How Immune-Cell Fate and Function are Determined by Metabolic Pathway Choice: The Bioenergetics Underlying the Immune Response. BioEssays 43 (2), e2000067. PubMed

Howard R., Kanetsky P. A., Egan K. M. (2019). Exploring the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Cancer. Sci. Rep. 9 (1), 19673. 10.1038/s41598-019-56218-z PubMed DOI PMC

Howlader N., Noone A. M., Krapcho M., Miller D., Brest A., Yu M., et al. (2020). SEER Cancer Statistics Review. Bethesda, MD: National Cancer Institute.

Ibegbu C. C., Xu Y.-X., Harris W., Maggio D., Miller J. D., Kourtis A. P. (2005). Expression of Killer Cell Lectin-like Receptor G1 on Antigen-Specific Human CD8+ T Lymphocytes during Active, Latent, and Resolved Infection and its Relation With CD57. J. Immunol. 174 (10), 6088–6094. 10.4049/jimmunol.174.10.6088 PubMed DOI

Itagaki K., Kaczmarek E., Lee Y. T., Tang I. T., Isal B., Adibnia Y., et al. (2015). Mitochondrial DNA Released by Trauma Induces Neutrophil Extracellular Traps. PLoS One 10 (3), e0120549. 10.1371/journal.pone.0120549 PubMed DOI PMC

Jacobs L. A., Shulman L. N. (2017). Follow-Up Care of Cancer Survivors: Challenges and Solutions. Lancet Oncol. 18 (1), e19–e29. 10.1016/s1470-2045(16)30386-2 PubMed DOI

Jaiswal S., Fontanillas P., Flannick J., Manning A., Grauman P. V., Mar B. G., et al. (2014). Age-Related Clonal Hematopoiesis Associated With Adverse Outcomes. N. Engl. J. Med. 371 (26), 2488–2498. 10.1056/nejmoa1408617 PubMed DOI PMC

Jaiswal S., Natarajan P., Silver A. J., Gibson C. J., Bick A. G., Shvartz E., et al. (2017). Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N. Engl. J. Med. 377 (2), 111–121. 10.1056/nejmoa1701719 PubMed DOI PMC

Jang Y.-Y., Sharkis S. J. (2007). A Low Level of Reactive Oxygen Species Selects for Primitive Hematopoietic Stem Cells that May Reside in the Low-Oxygenic Niche. Blood 110 (8), 3056–3063. 10.1182/blood-2007-05-087759 PubMed DOI PMC

Jing Y., Shaheen E., Drake R. R., Chen N., Gravenstein S., Deng Y. (2009). Aging is Associated with a Numerical and Functional Decline in Plasmacytoid Dendritic Cells, Whereas Myeloid Dendritic Cells are Relatively Unaltered in Human Peripheral Blood. Hum. Immunol. 70 (10), 777–784. 10.1016/j.humimm.2009.07.005 PubMed DOI PMC

Johnson N. D., Conneely K. N. (2019). The Role of DNA Methylation and Hydroxymethylation in Immunosenescence. Ageing Res. Rev. 51, 11–23. 10.1016/j.arr.2019.01.011 PubMed DOI

Jose S. S., Bendickova K., Kepak T., Krenova Z., Fric J. (2017). Chronic Inflammation in Immune Aging: Role of Pattern Recognition Receptor Crosstalk With the Telomere Complex? Front. Immunol. 8, 1078. 10.3389/fimmu.2017.01078 PubMed DOI PMC

Jose S. S., Tidu F., Burilova P., Kepak T., Bendickova K., Fric J. (2018). The Telomerase Complex Directly Controls Hematopoietic Stem Cell Differentiation and Senescence in an Induced Pluripotent Stem Cell Model of Telomeropathy. Front. Genet. 9, 345. 10.3389/fgene.2018.00345 PubMed DOI PMC

Jylhävä J., Nevalainen T., Marttila S., Jylhä M., Hervonen A., Hurme M. (2013). Characterization of the Role of Distinct Plasma Cell-free DNA Species in Age-Associated Inflammation and Frailty. Aging Cell 12 (3), 388–397. 10.1111/acel.12058 PubMed DOI

Kallemeijn M. J., Boots A. M. H., van der Klift M. Y., Brouwer E., Abdulahad W. H., Verhaar J. A. N., et al. (2017). Ageing and Latent CMV Infection Impact on Maturation, Differentiation and Exhaustion Profiles of T-Cell Receptor Gammadelta T-Cells. Sci. Rep. 7 (1), 5509. 10.1038/s41598-017-05849-1 PubMed DOI PMC

Kao T. W., Chen W. L., Han D. S., Huang Y. H., Chen C. L., Yang W. S. (2016). Examining How p16(INK4a) Expression Levels are Linked to Handgrip Strength in the Elderly. Sci. Rep. 6, 31905. 10.1038/srep31905 PubMed DOI PMC

Kared H., Martelli S., Ng T. P., Pender S. L. F., Larbi A. (2016). CD57 in Human Natural Killer Cells and T-Lymphocytes. Cancer Immunol. Immunother. 65 (4), 441–452. 10.1007/s00262-016-1803-z PubMed DOI PMC

Kaszubowska L., Kaczor J. J., Hak L., Dettlaff-Pokora A., Szarynska M., Kmiec Z. (2011). Sensitivity of Natural Killer Cells to Activation in the Process of Ageing is Related to the Oxidative and Inflammatory Status of the Elderly. J. Physiol. Pharmacol. 62 (1), 101–109. PubMed

Kim H., Kim H.-S., Youn J.-C., Shin E.-C., Park S. (2011). Serum Cytokine Profiles in Healthy Young and Elderly Population Assessed Using Multiplexed Bead-Based Immunoassays. J. Transl. Med. 9, 113. 10.1186/1479-5876-9-113 PubMed DOI PMC

Koch S., Larbi A., Derhovanessian E., Özcelik D., Naumova E., Pawelec G. (2008). Multiparameter Flow Cytometric Analysis of CD4 and CD8 T Cell Subsets in Young and Old People. Immun. Ageing 5, 6. 10.1186/1742-4933-5-6 PubMed DOI PMC

Koch S., Larbi A., Ozcelik D., Solana R., Gouttefangeas C., Attig S., et al. (2007). Cytomegalovirus Infection: a Driving Force in Human T Cell Immunosenescence. Ann. N. Y. Acad. Sci. 1114, 23–35. 10.1196/annals.1396.043 PubMed DOI

Koelman L., Pivovarova-Ramich O., Pfeiffer A. F. H., Grune T., Aleksandrova K. (2019). Cytokines for Evaluation of Chronic Inflammatory Status in Ageing Research: Reliability and Phenotypic Characterisation. Immun. Ageing 16, 11. 10.1186/s12979-019-0151-1 PubMed DOI PMC

Kovaiou R. D., Weiskirchner I., Keller M., Pfister G., Cioca D. P., Grubeck-Loebenstein B. (2005). Age-Related Differences in Phenotype and Function of CD4+ T Cells Are Due to a Phenotypic Shift from Naive to Memory Effector CD4+ T Cells. Int. Immunol. 17 (10), 1359–1366. 10.1093/intimm/dxh314 PubMed DOI

Krater M., Jacobi A., Otto O., Tietze S., Muller K., Poitz D. M., et al. (2017). Bone Marrow Niche-Mimetics Modulate HSPC Function via Integrin Signaling. Sci. Rep. 7 (1), 2549. 10.1038/s41598-017-02352-5 PubMed DOI PMC

Kuo C. L., Pilling L. C., Kuchel G. A., Ferrucci L., Melzer D. (2019). Telomere Length and Aging-Related Outcomes in Humans: A Mendelian Randomization Study in 261,000 Older Participants. Aging Cell 18 (6), e13017. 10.1111/acel.13017 PubMed DOI PMC

Kuranda K., Vargaftig J., de la Rochere P., Dosquet C., Charron D., Bardin F., et al. (2011). Age-related Changes in Human Hematopoietic Stem/Progenitor Cells. Aging Cell 10 (3), 542–546. 10.1111/j.1474-9726.2011.00675.x PubMed DOI

Lane-Cordova A. D., Ranadive S. M., Kappus R. M., Cook M. D., Phillips S. A., Woods J. A., et al. (2016). Aging, not Age-Associated Inflammation, Determines Blood Pressure and Endothelial Responses to Acute Inflammation. J. Hypertens. 34 (12), 2402–2409. 10.1097/hjh.0000000000001103 PubMed DOI

Lanna A., Henson S. M., Escors D., Akbar A. N. (2014). The Kinase P38 Activated by the Metabolic Regulator AMPK and Scaffold TAB1 Drives the Senescence of Human T Cells. Nat. Immunol. 15 (10), 965–972. 10.1038/ni.2981 PubMed DOI PMC

Larbi A., Fulop T. (2014). From “Truly Naïve” to “Exhausted Senescent” T Cells: When Markers Predict Functionality. Cytometry 85 (1), 25–35. 10.1002/cyto.a.22351 PubMed DOI

Lázničková P., Kepák T., Hortová-Kohoutková M., Horváth L., Sheardová K., Marciniak R., et al. (2020). Childhood Survivors of High-Risk Neuroblastoma Show Signs of Immune Recovery and not Immunosenescence. Eur. J. Immunol. 50 (12), 2092–2094. 10.1002/eji.202048541 PubMed DOI PMC

Le Garff-Tavernier M., Béziat V., Decocq J., Siguret V., Gandjbakhch F., Pautas E., et al. (2010). Human NK Cells Display Major Phenotypic and Functional Changes Over the Life Span. Aging Cell 9 (4), 527–535. 10.1111/j.1474-9726.2010.00584.x PubMed DOI

Leal L. G., Lopes M. A., Batista M. L., Jr (2018). Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases. Front. Physiol. 9, 1307. 10.3389/fphys.2018.01307 PubMed DOI PMC

Lee I. H. (2019). Mechanisms and Disease Implications of Sirtuin-Mediated Autophagic Regulation. Exp. Mol. Med. 51 (9), 1–11. 10.1038/s12276-019-0302-7 PubMed DOI PMC

Lee J.-J., Nam C.-E., Cho S.-H., Park K.-S., Chung I.-J., Kim H.-J. (2003). Telomere Length Shortening in Non-Hodgkin’s Lymphoma Patients Undergoing Chemotherapy. Ann. Hematol. 82 (8), 492–495. 10.1007/s00277-003-0691-4 PubMed DOI

Lee S. T., Jang J. H., Cheong J.-W., Kim J. S., Maemg H.-Y., Hahn J. S., et al. (2002). Treatment of High-Risk Acute Myelogenous Leukaemia by Myeloablative Chemoradiotherapy Followed by Co-infusion of T Cell-Depleted Haematopoietic Stem Cells and Culture-Expanded Marrow Mesenchymal Stem Cells from a Related Donor with One Fully Mismatched Human Leucocyte Antigen Haplotype. Br. J. Haematol. 118 (4), 1128–1131. 10.1046/j.1365-2141.2002.03767.x PubMed DOI

Lee Y.-h., Kim S. R., Han D. H., Yu H. T., Han Y. D., Kim J. H., et al. (2019). Senescent T Cells Predict the Development of Hyperglycemia in Humans. Diabetes 68 (1), 156–162. 10.2337/db17-1218 PubMed DOI

Li P., Hou M., Lou F., Björkholm M., Xu D. (2012). Telomere Dysfunction Induced by Chemotherapeutic Agents and Radiation in Normal Human Cells. Int. J. Biochem. Cell Biol. 44 (9), 1531–1540. 10.1016/j.biocel.2012.06.020 PubMed DOI

Li Q., Ding S., Wang Y. M., Xu X., Shen Z., Fu R., et al. (2017). Age-Associated Alteration in Th17 Cell Response is Related to Endothelial Cell Senescence and Atherosclerotic Cerebral Infarction. Am. J. Transl. Res. 9 (11), 5160–5168. PubMed PMC

Linehan E., Fitzgerald D. (2015). Ageing and the Immune System: Focus on Macrophages. Eur. J. Microbiol. Immunol. 5 (1), 14–24. 10.1556/eujmi-d-14-00035 PubMed DOI PMC

Liu W., Liu Y., Yang Y., Ou W., Chen X., Huang B., et al. (2018). Metabolic Biomarkers of Aging and Aging-Related Diseases in Chinese Middle-Aged and Elderly Men. J. Nutr. Health Aging 22 (10), 1189–1197. 10.1007/s12603-018-1062-0 PubMed DOI

Liu Y., Sanoff H. K., Cho H., Burd C. E., Torrice C., Ibrahim J. G., et al. (2009). Expression of p16INK4ain Peripheral Blood T-Cells is a Biomarker of Human Aging. Aging Cell 8 (4), 439–448. 10.1111/j.1474-9726.2009.00489.x PubMed DOI PMC

López-Otín C., Blasco M. A., Partridge L., Serrano M., Kroemer G. (2013). The Hallmarks of Aging. Cell 153 (6), 1194–1217. 10.1016/j.cell.2013.05.039 PubMed DOI PMC

Lorenzi M. F., Xie L., Rogers P. C., Pritchard S., Goddard K., McBride M. L. (2011). Hospital-related Morbidity Among Childhood Cancer Survivors in British Columbia, Canada: Report of the Childhood, Adolescent, Young Adult Cancer Survivors (CAYACS) Program. Int. J. Cancer 128 (7), 1624–1631. 10.1002/ijc.25751 PubMed DOI

Lu Y., Tan C. T. Y., Nyunt M. S. Z., Mok E. W. H., Camous X., Kared H., et al. (2016). Inflammatory and Immune Markers Associated with Physical Frailty Syndrome: Findings from Singapore Longitudinal Aging Studies. Oncotarget 7 (20), 28783–28795. 10.18632/oncotarget.8939 PubMed DOI PMC

Ma S., Wang C., Mao X., Hao Y. (2019). B Cell Dysfunction Associated With Aging and Autoimmune Diseases. Front. Immunol. 10, 318. 10.3389/fimmu.2019.00318 PubMed DOI PMC

Malaguarnera L. (2019). Influence of Resveratrol on the Immune Response. Nutrients 11 (5). 10.3390/nu11050946 PubMed DOI PMC

Marengoni A., von Strauss E., Rizzuto D., Winblad B., Fratiglioni L. (2009). The Impact of Chronic Multimorbidity and Disability on Functional Decline and Survival in Elderly Persons. A Community-Based, Longitudinal Study. J. Intern. Med. 265 (2), 288–295. 10.1111/j.1365-2796.2008.02017.x PubMed DOI

Martin-Montalvo A., Mercken E. M., Mitchell S. J., Palacios H. H., Mote P. L., Scheibye-Knudsen M., et al. (2013). Metformin Improves Healthspan and Lifespan in Mice. Nat. Commun. 4, 2192. 10.1038/ncomms3192 PubMed DOI PMC

Martínez-Zamudio R. I., Dewald H. K., Vasilopoulos T., Gittens-Williams L., Fitzgerald-Bocarsly P., Herbig U. (2021). Senescence-associated β-Galactosidase Reveals the Abundance of Senescent CD8+ T Cells in Aging Humans. Aging Cell 20 (5), e13344. 10.1111/acel.13344 PubMed DOI PMC

Masopustová A., Jehlička P., Huml M., Votava T., Trefil L., Kreslová M., et al. (2018). Plethysmographic and Biochemical Markers in the Diagnosis of Endothelial Dysfunction in Pediatric Acute Lymphoblastic Leukemia Survivors - New Applications. Physiol. Res. 67 (6), 903–909. 10.33549/physiolres.933754 PubMed DOI

Mau T., Yung R. (2018). Adipose Tissue Inflammation in Aging. Exp. Gerontol. 105, 27–31. 10.1016/j.exger.2017.10.014 PubMed DOI PMC

McFarlin B. K., Flynn M. G., Campbell W. W., Craig B. A., Robinson J. P., Stewart L. K., et al. (2006). Physical Activity Status, but not Age, Influences Inflammatory Biomarkers and Toll-Like Receptor 4. Gerontol. A. Biol. Sci. Med. Sci. 61 (4), 388–393. 10.1093/gerona/61.4.388 PubMed DOI

Mertens A. C., Liu Q., Neglia J. P., Wasilewski K., Leisenring W., Armstrong G. T., et al. (2008). Cause-Specific Late Mortality Among 5-Year Survivors of Childhood Cancer: the Childhood Cancer Survivor Study. JNCI J. Natl. Cancer Inst. 100 (19), 1368–1379. 10.1093/jnci/djn310 PubMed DOI PMC

Metcalf T. U., Wilkinson P. A., Cameron M. J., Ghneim K., Chiang C., Wertheimer A. M., et al. (2017). Human Monocyte Subsets are Transcriptionally and Functionally Altered in Aging in Response to Pattern Recognition Receptor Agonists. J. Immunol. 199 (4), 1405–1417. 10.4049/jimmunol.1700148 PubMed DOI PMC

Milan-Mattos J. C., Anibal F. F., Perseguini N. M., Minatel V., Rehder-Santos P., Castro C. A., et al. (2019). Effects of Natural Aging and Gender on Pro-Inflammatory Markers. Braz. J. Med. Biol. Res. 52 (9), e8392. 10.1590/1414-431x20198392 PubMed DOI PMC

Milkovic L., Cipak Gasparovic A., Cindric M., Mouthuy P. A., Zarkovic N. (2019). Short Overview of ROS as Cell Function Regulators and Their Implications in Therapy Concepts. Cells 8 (8), 793. 10.3390/cells8080793 PubMed DOI PMC

Miyamoto-Mikami E., Sato K., Kurihara T., Hasegawa N., Fujie S., Fujita S., et al. (2015). Endurance Training-Induced Increase in Circulating Irisin Levels is Associated With Reduction of Abdominal Visceral Fat in Middle-Aged and Older Adults. PLoS One 10 (3), e0120354. 10.1371/journal.pone.0120354 PubMed DOI PMC

Møller H. J., Frikke-Schmidt R., Moestrup S. K., Nordestgaard B. G., Tybjærg-Hansen A. (2011). Serum Soluble CD163 Predicts Risk of Type 2 Diabetes in the General Population. Clin. Chem. 57 (2), 291–297. 10.1373/clinchem.2010.154724 PubMed DOI

Montecino-Rodriguez E., Berent-Maoz B., Dorshkind K. (2013). Causes, Consequences, and Reversal of Immune System Aging. J. Clin. Invest. 123 (3), 958–965. 10.1172/jci64096 PubMed DOI PMC

Montiel Rojas D., Nilsson A., Ponsot E., Brummer R. J., Fairweather-Tait S., Jennings A., et al. (2018). Short Telomere Length is Related to Limitations in Physical Function in Elderly European Adults. Front. Physiol. 9, 1110. 10.3389/fphys.2018.01110 PubMed DOI PMC

Morrisette-Thomas V., Cohen A. A., Fülöp T., Riesco É., Legault V., Li Q., et al. (2014). Inflamm-Aging Does Not Simply Reflect Increases in Pro-Inflammatory Markers. Mech. Ageing Dev. 139, 49–57. 10.1016/j.mad.2014.06.005 PubMed DOI PMC

Morrison S. J., Prowse K. R., Ho P., Weissman I. L. (1996). Telomerase Activity in Hematopoietic Cells Is Associated With Self-Renewal Potential. Immunity 5 (3), 207–216. 10.1016/s1074-7613(00)80316-7 PubMed DOI

Mostoufi-Moab S., Seidel K., Leisenring W. M., Armstrong G. T., Oeffinger K. C., Stovall M., et al. (2016). Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J. Clin. Oncol. 34 (27), 3240–3247. 10.1200/jco.2016.66.6545 PubMed DOI PMC

Munz F., Lopez Perez R., Trinh T., Sisombath S., Weber K. J., Wuchter P., et al. (2018). Human Mesenchymal Stem Cells Lose Their Functional Properties after Paclitaxel Treatment. Sci. Rep. 8 (1), 312. 10.1038/s41598-017-18862-1 PubMed DOI PMC

Murray M. A., Chotirmall S. H. (2015). The Impact of Immunosenescence on Pulmonary Disease. Mediators Inflamm. 2015, 692546. 10.1155/2015/692546 PubMed DOI PMC

Nazir Y., Hussain S. A., Abdul Hamid A., Song Y. (2018). Probiotics and Their Potential Preventive and Therapeutic Role for Cancer, High Serum Cholesterol, and Allergic and HIV Diseases. Biomed. Research Int. 2018, 3428437. 10.1155/2018/3428437 PubMed DOI PMC

Ness K. K., Armstrong G. T., Kundu M., Wilson C. L., Tchkonia T., Kirkland J. L. (2015). Frailty in Childhood Cancer Survivors. Cancer 121 (10), 1540–1547. 10.1002/cncr.29211 PubMed DOI PMC

Ness K. K., Kirkland J. L., Gramatges M. M., Wang Z., Kundu M., McCastlain K., et al. (2018). Premature Physiologic Aging as a Paradigm for Understanding Increased Risk of Adverse Health Across the Lifespan of Survivors of Childhood Cancer. J. Clin. Oncol. 36 (21), 2206–2215. 10.1200/jco.2017.76.7467 PubMed DOI PMC

Ness K. K., Krull K. R., Jones K. E., Mulrooney D. A., Armstrong G. T., Green D. M., et al. (2013). Physiologic Frailty as a Sign of Accelerated Aging Among Adult Survivors of Childhood Cancer: a Report from the St Jude Lifetime Cohort Study. J. Clin. Oncol. 31 (36), 4496–4503. 10.1200/jco.2013.52.2268 PubMed DOI PMC

Njemini R., Bautmans I., Onyema O. O., Van Puyvelde K., Demanet C., Mets T. (2011). Circulating Heat Shock Protein 70 in Health, Aging and Disease. BMC Immunol. 12, 24. 10.1186/1471-2172-12-24 PubMed DOI PMC

Oeffinger K. C., Mertens A. C., Sklar C. A., Kawashima T., Hudson M. M., Meadows A. T., et al. (2006). Chronic Health Conditions in Adult Survivors of Childhood Cancer. N. Engl. J. Med. 355 (15), 1572–1582. 10.1056/nejmsa060185 PubMed DOI

Ogawa K., Suzuki K., Okutsu M., Yamazaki K., Shinkai S. (2008). The Association of Elevated Reactive Oxygen Species Levels from Neutrophils With Low-Grade Inflammation in the Elderly. Immun. Ageing 5, 13. 10.1186/1742-4933-5-13 PubMed DOI PMC

Olsson J., Wikby A., Johansson B., Löfgren S., Nilsson B. O., Ferguson F. G. (2000). Age-related Change in Peripheral Blood T-Lymphocyte Subpopulations and Cytomegalovirus Infection in the Very Old: the Swedish Longitudinal OCTO Immune Study. Mech. Ageing Dev. 121 (1–3), 187–201. 10.1016/s0047-6374(00)00210-4 PubMed DOI

Ong S. M., Hadadi E., Dang T. M., Yeap W. H., Tan C. T., Ng T. P., et al. (2018). The Pro-Inflammatory Phenotype of the Human Non-Classical Monocyte Subset is Attributed to Senescence. Cell Death Dis. 9 (3), 266. 10.1038/s41419-018-0327-1 PubMed DOI PMC

Ortmann W., Kolaczkowska E. (2018). Age is the Work of Art? Impact of Neutrophil and Organism Age on Neutrophil Extracellular Trap Formation. Cell Tissue Res. 371 (3), 473–488. 10.1007/s00441-017-2751-4 PubMed DOI PMC

Ostan R., Bucci L., Capri M., Salvioli S., Scurti M., Pini E., et al. (2008). Immunosenescence and Immunogenetics of Human Longevity. Neuroimmunomodulation 15 (4-6), 224–240. 10.1159/000156466 PubMed DOI

Palmeri M., Misiano G., Malaguarnera M., Forte G. I., Vaccarino L., Milano S., et al. (2012). Cytokine Serum Profile in a Group of Sicilian Nonagenarians. J. Immunoassay Immunochem. 33 (1), 82–90. 10.1080/15321819.2011.601781 PubMed DOI

Panda A., Qian F., Mohanty S., van Duin D., Newman F. K., Zhang L., et al. (2010). Age-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response. J. Immunol. 184 (5), 2518–2527. 10.4049/jimmunol.0901022 PubMed DOI PMC

Pang W. W., Price E. A., Sahoo D., Beerman I., Maloney W. J., Rossi D. J., et al. (2011). Human Bone Marrow Hematopoietic Stem Cells Are Increased in Frequency and Myeloid-Biased With Age. Proc. Natl. Acad. Sci. 108 (50), 20012–20017. 10.1073/pnas.1116110108 PubMed DOI PMC

Pansarasa O., Pistono C., Davin A., Bordoni M., Mimmi M. C., Guaita A., et al. (2019). Altered Immune System in Frailty: Genetics and Diet May Influence Inflammation. Ageing Res. Rev. 54, 100935. 10.1016/j.arr.2019.100935 PubMed DOI

Parish S. T., Wu J. E., Effros R. B. (2010). Sustained CD28 Expression Delays Multiple Features of Replicative Senescence in Human CD8 T Lymphocytes. J. Clin. Immunol. 30 (6), 798–805. 10.1007/s10875-010-9449-7 PubMed DOI PMC

Partridge L., Deelen J., Slagboom P. E. (2018). Facing up to the Global Challenges of Ageing. Nature 561 (7721), 45–56. 10.1038/s41586-018-0457-8 PubMed DOI

Patel S. R., Ortin M., Cohen B. J., Borrow R., Irving D., Sheldon J., et al. (2007). Revaccination of Children After Completion of Standard Chemotherapy for Acute Leukemia. Clin. Infect. Dis. 44 (5), 635–642. 10.1086/511636 PubMed DOI

Pawelec G. (1999). Immunosenescence: Impact in the Young as Well as the Old? Mech. Ageing Dev. 108 (1), 1–7. 10.1016/s0047-6374(99)00010-x PubMed DOI

Pedersen M., Bruunsgaard H., Weis N., Hendel H. W., Andreassen B. U., Eldrup E., et al. (2003). Circulating Levels of TNF-Alpha and IL-6-relation to Truncal Fat Mass and Muscle Mass in Healthy Elderly Individuals and in Patients with Type-2 Diabetes. Mech. Ageing Develop. 124 (4), 495–502. 10.1016/s0047-6374(03)00027-7 PubMed DOI

Pérez-Cabezas B., Naranjo-Gómez M., Fernández M. A., Grífols J. R., Pujol-Borrell R., Borràs F. E. (2007). Reduced Numbers of Plasmacytoid Dendritic Cells in Aged Blood Donors. Exp. Gerontol. 42 (10), 1033–1038. 10.1016/j.exger.2007.05.010 PubMed DOI

Perkins J. L., Chen Y., Harris A., Diller L., Stovall M., Armstrong G. T., et al. (2014). Infections Among Long-Term Survivors of Childhood and Adolescent Cancer: A Report From the Childhood Cancer Survivor Study. Cancer 120 (16), 2514–2521. 10.1002/cncr.28763 PubMed DOI PMC

Perkins J. L., Harris A., Pozos T. C. (2017). Immune Dysfunction After Completion of Childhood Leukemia Therapy. J. Pediatr. Hematol. Oncol. 39 (1), 1–5. 10.1097/mph.0000000000000697 PubMed DOI

Petersen A. M., Pedersen B. K. (1985). The Anti-Inflammatory Effect of Exercise. J. Appl. Physiol. 98 (4), 1154–1162. 10.1152/japplphysiol.00164.2004 PubMed DOI

Pifferi F., Terrien J., Perret M., Epelbaum J., Blanc S., Picq J. L., et al. (2019). Promoting Healthspan and Lifespan with Caloric Restriction in Primates. Commun. Biol. 2, 107. 10.1038/s42003-019-0348-z PubMed DOI PMC

Pinti M., Appay V., Campisi J., Frasca D., Fülöp T., Sauce D., et al. (2016). Aging of the Immune System: Focus on Inflammation and Vaccination. Eur. J. Immunol. 46 (10), 2286–2301. 10.1002/eji.201546178 PubMed DOI PMC

Pinti M., Cevenini E., Nasi M., De Biasi S., Salvioli S., Monti D., et al. (2014). Circulating Mitochondrial DNA Increases with Age and is a Familiar Trait: Implications for “Inflamm-Aging”. Eur. J. Immunol. 44 (5), 1552–1562. 10.1002/eji.201343921 PubMed DOI

Puzianowska-Kuźnicka M., Owczarz M., Wieczorowska-Tobis K., Nadrowski P., Chudek J., Slusarczyk P., et al. (2016). Interleukin-6 and C-Reactive Protein, Successful Aging, and Mortality: The PolSenior Study. Immun. Ageing 13, 21. 10.1186/s12979-016-0076-x PubMed DOI PMC

Qian F., Wang X., Zhang L., Lin A., Zhao H., Fikrig E., et al. (2011). Impaired Interferon Signaling in Dendritic Cells from Older Donors Infected In Vitro With West Nile Virus. J. Infect. Dis. 203 (10), 1415–1424. 10.1093/infdis/jir048 PubMed DOI PMC

Qin L., Jing X., Qiu Z., Cao W., Jiao Y., Routy J.-P., et al. (2016). Aging of Immune System: Immune Signature from Peripheral Blood Lymphocyte Subsets in 1068 Healthy Adults. Aging 8 (5), 848–859. 10.18632/aging.100894 PubMed DOI PMC

Reulen R. C., Winter D. L., Frobisher C., Lancashire E. R., Stiller C. A., Jenney M. E., et al. (2010). Long-Term Cause-Specific Mortality Among Survivors of Childhood Cancer. JAMA 304 (2), 172–179. 10.1001/jama.2010.923 PubMed DOI

Ross J. A., Oeffinger K. C., Davies S. M., Mertens A. C., Langer E. K., Kiffmeyer W. R., et al. (2004). Genetic Variation in the Leptin Receptor Gene and Obesity in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study. J. Clin. Oncol. 22 (17), 3558–3562. 10.1200/jco.2004.11.152 PubMed DOI

Rubtsov A. V., Rubtsova K., Fischer A., Meehan R. T., Gillis J. Z., Kappler J. W., et al. (2011). Toll-like Receptor 7 (TLR7)-Driven Accumulation of a Novel CD11c+ B-Cell Population Is Important for the Development of Autoimmunity. Blood 118 (5), 1305–1315. 10.1182/blood-2011-01-331462 PubMed DOI PMC

Rundberg Nilsson A., Soneji S., Adolfsson S., Bryder D., Pronk C. J. (2016). Human and Murine Hematopoietic Stem Cell Aging is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias. PLoS One 11 (7), e0158369. 10.1371/journal.pone.0158369 PubMed DOI PMC

Rusanova I., Diaz-Casado M. E., Fernandez-Ortiz M., Aranda-Martinez P., Guerra-Librero A., Garcia-Garcia F. J., et al. (2018). Analysis of Plasma MicroRNAs as Predictors and Biomarkers of Aging and Frailty in Humans. Oxid Med. Cell Longev. 2018, 7671850. 10.1155/2018/7671850 PubMed DOI PMC

Sadurska E., Zaucha-Prażmo A., Brodzisz A., Kowalczyk J., Ben-Skowronek I. (2018). Premature Atherosclerosis After Treatment for Acute Lymphoblastic Leukemia in Childhood. Ann. Agric. Environ. Med. 25 (1), 71–76. 10.5604/12321966.1230680 PubMed DOI

Saldias M. P., Fernandez C., Morgan A., Diaz C., Morales D., Jana F., et al. (2017). Aged Blood Factors Decrease Cellular Responses Associated with Delayed Gingival Wound Repair. PLoS One 12 (9), e0184189. 10.1371/journal.pone.0184189 PubMed DOI PMC

Sanders J. L., Cauley J. A., Boudreau R. M., Zmuda J. M., Strotmeyer E. S., Opresko P. L., et al. (2009). Leukocyte Telomere Length is Not Associated With BMD, Osteoporosis, or Fracture in Older Adults: Results From the Health, Aging and Body Composition Study. J. Bone Miner. Res. 24 (9), 1531–1536. 10.1359/jbmr.090318 PubMed DOI PMC

Sandmand M., Bruunsgaard H., Kemp K., Andersen-Ranberg K., Schroll M., Jeune B. (2003). High Circulating Levels of Tumor Necrosis Factor-α in Centenarians Are Not Associated with Increased Production in T Lymphocytes. Gerontology 49 (3), 155–160. 10.1159/000069174 PubMed DOI

Sapey E., Greenwood H., Walton G., Mann E., Love A., Aaronson N., et al. (2014). Phosphoinositide 3-kinase Inhibition Restores Neutrophil Accuracy in the Elderly: Toward Targeted Treatments for Immunosenescence. Blood 123 (2), 239–248. 10.1182/blood-2013-08-519520 PubMed DOI PMC

Sauce D., Dong Y., Campillo-Gimenez L., Casulli S., Bayard C., Autran B., et al. (2017). Reduced Oxidative Burst by Primed Neutrophils in the Elderly Individuals is Associated With Increased Levels of the CD16bright/CD62Ldim Immunosuppressive Subset. Gerona 72 (2), 163–172. 10.1093/gerona/glw062 PubMed DOI

Saule P., Trauet J., Dutriez V., Lekeux V., Dessaint J.-P., Labalette M. (2006). Accumulation of Memory T Cells From Childhood to Old Age: Central and Effector Memory Cells in CD4+ versus Effector Memory and Terminally Differentiated Memory Cells in CD8+ Compartment. Mech. Ageing Develop. 127 (3), 274–281. 10.1016/j.mad.2005.11.001 PubMed DOI

Schröder C. P., Wisman G. B., de Jong S., van der Graaf W. T., Ruiters M. H., Mulder N. H., et al. (2001). Telomere Length in Breast Cancer Patients Before and After Chemotherapy With or Without Stem Cell Transplantation. Br. J. Cancer 84 (10), 1348–1353. 10.1054/bjoc.2001.1803 PubMed DOI PMC

Seidler S., Zimmermann H. W., Bartneck M., Trautwein C., Tacke F. (2010). Age-dependent Alterations of Monocyte Subsets and Monocyte-Related Chemokine Pathways in Healthy Adults. BMC Immunol. 11, 30. 10.1186/1471-2172-11-30 PubMed DOI PMC

Shaw A. C., Goldstein D. R., Montgomery R. R. (2013). Age-Dependent Dysregulation of Innate Immunity. Nat. Rev. Immunol. 13 (12), 875–887. 10.1038/nri3547 PubMed DOI PMC

Shaw A. C., Joshi S., Greenwood H., Panda A., Lord J. M. (2010). Aging of the Innate Immune System. Curr. Opin. Immunol. 22 (4), 507–513. 10.1016/j.coi.2010.05.003 PubMed DOI PMC

Shetty A. K., Winter M. A. (2012). Immunization of Children Receiving Immunosuppressive Therapy for Cancer or Hematopoietic Stem Cell Transplantation. Ochsner J. 12 (3), 228–243. PubMed PMC

Simell B., Vuorela A., Ekström N., Palmu A., Reunanen A., Meri S., et al. (2011). Aging Reduces the Functionality of Anti-Pneumococcal Antibodies and the Killing of Streptococcus pneumoniae by Neutrophil Phagocytosis. Vaccine 29 (10), 1929–1934. 10.1016/j.vaccine.2010.12.121 PubMed DOI

Simnica D., Akyuz N., Schliffke S., Mohme M., Wenserski L. V., Mährle T., et al. (2019). T Cell Receptor Next-Generation Sequencing Reveals Cancer-Associated Repertoire Metrics and Reconstitution after Chemotherapy in Patients with Hematological and Solid Tumors. Oncoimmunology 8 (11), e1644110. 10.1080/2162402x.2019.1644110 PubMed DOI PMC

Slusher A. L., Zuniga T. M., Acevedo E. O. (2019). Inflamm-Aging Is Associated with Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT Following LPS Stimulation. Mediators Inflamm. 2019, 2324193. 10.1155/2019/2324193 PubMed DOI PMC

Smitherman A. B., Wood W. A., Mitin N., Ayer Miller V. L., Deal A. M., Davis I. J., et al. (2020). Accelerated Aging Among Childhood, Adolescent, and Young Adult Cancer Survivors is Evidenced by Increased Expression of p16 INK4a and Frailty. Cancer 126 (22), 4975–4983. 10.1002/cncr.33112 PubMed DOI PMC

Solana R., Tarazona R., Gayoso I., Lesur O., Dupuis G., Fulop T. (2012). Innate Immunosenescence: Effect of Aging on Cells and Receptors of the Innate Immune System in Humans. Semin. Immunol. 24 (5), 331–341. 10.1016/j.smim.2012.04.008 PubMed DOI

Song N., Li Z., Qin N., Howell C. R., Wilson C. L., Easton J., et al. (2020). Shortened Leukocyte Telomere Length Associates with an Increased Prevalence of Chronic Health Conditions Among Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort. Clin. Cancer Res. 26 (10), 2362–2371. 10.1158/1078-0432.ccr-19-2503 PubMed DOI PMC

Song Z., von Figura G., Liu Y., Kraus J. M., Torrice C., Dillon P., et al. (2010). Lifestyle Impacts on the Aging-Associated Expression of Biomarkers of DNA Damage and Telomere Dysfunction in Human Blood. Aging Cell 9 (4), 607–615. 10.1111/j.1474-9726.2010.00583.x PubMed DOI PMC

Spazzafumo L., Mensà E., Matacchione G., Galeazzi T., Zampini L., Recchioni R., et al. (2017). Age-Related Modulation of Plasmatic Beta-Galactosidase Activity in Healthy Subjects and in Patients Affected by T2DM. Oncotarget 8 (55), 93338–93348. 10.18632/oncotarget.21848 PubMed DOI PMC

Splunter M. V., Perdijk O., Fick-Brinkhof H., Floris-Vollenbroek E. G., Meijer B., Brugman S., et al. (2019). Plasmacytoid Dendritic Cell and Myeloid Dendritic Cell Function in Ageing: A Comparison between Elderly and Young Adult Women. PLoS One 14 (12), e0225825. 10.1371/journal.pone.0225825 PubMed DOI PMC

Spyridopoulos I., Hoffmann J., Aicher A., Brümmendorf T. H., Doerr H. W., Zeiher A. M., et al. (2009). Accelerated Telomere Shortening in Leukocyte Subpopulations of Patients With Coronary Heart Disease. Circulation 120 (14), 1364–1372. 10.1161/circulationaha.109.854299 PubMed DOI

Squillaro T., Peluso G., Galderisi U. (2016). Clinical Trials With Mesenchymal Stem Cells: An Update. Cell Transpl. 25 (5), 829–848. 10.3727/096368915x689622 PubMed DOI

Sridharan A., Esposo M., Kaushal K., Tay J., Osann K., Agrawal S., et al. (2011). Age-Associated Impaired Plasmacytoid Dendritic Cell Functions Lead to Decreased CD4 and CD8 T Cell Immunity. Age 33 (3), 363–376. 10.1007/s11357-010-9191-3 PubMed DOI PMC

Steensberg A., Fischer C. P., Keller C., Møller K., Pedersen B. K. (2003). IL-6 Enhances Plasma IL-1ra, IL-10, and Cortisol in Humans. Am. J. Physiol. Endocrinol. Metab. 285 (2), E433–E437. 10.1152/ajpendo.00074.2003 PubMed DOI

Steliarova-Foucher E., Colombet M., Ries L. A. G., Moreno F., Dolya A., Bray F., et al. (2017). International Incidence of Childhood Cancer, 2001-10: A Population-Based Registry Study. Lancet Oncol. 18 (6), 719–731. 10.1016/S1470-2045(17)30186-9 PubMed DOI PMC

Suarez-Álvarez B., Rodríguez R. M., Schlangen K., Raneros A. B., Márquez-Kisinousky L., Fernández A. F., et al. (2017). Phenotypic Characteristics of Aged CD4+ CD28null T Lymphocytes are Determined by Changes in the Whole-Genome DNA Methylation Pattern. Aging Cell 16 (2), 293–303. 10.1111/acel.12552 PubMed DOI PMC

Sulicka J., Surdacki A., Mikołajczyk T., Strach M., Gryglewska B., Ćwiklińska M., et al. (2013). Elevated Markers of Inflammation and Endothelial Activation and Increased Counts of Intermediate Monocytes in Adult Survivors of Childhood Acute Lymphoblastic Leukemia. Immunobiology 218 (5), 810–816. 10.1016/j.imbio.2012.09.003 PubMed DOI

Sulicka-Grodzicka J., Surdacki A., Seweryn M., Mikołajczyk T., Rewiuk K., Guzik T., et al. (2021). Low-grade Chronic Inflammation and Immune Alterations in Childhood and Adolescent Cancer Survivors: A Contribution to Accelerated Aging? Cancer Med. 10 (5), 1772–1782. 10.1002/cam4.3788 PubMed DOI PMC

Talukdar S., Oh D. Y., Bandyopadhyay G., Li D., Xu J., McNelis J., et al. (2012). Neutrophils Mediate Insulin Resistance in Mice Fed a High-Fat Diet through Secreted Elastase. Nat. Med. 18 (9), 1407–1412. 10.1038/nm.2885 PubMed DOI PMC

Teo Y. V., Capri M., Morsiani C., Pizza G., Faria A. M. C., Franceschi C., et al. (2019). Cell-Free DNA as a Biomarker of Aging. Aging Cell 18 (1), e12890. 10.1111/acel.12890 PubMed DOI PMC

Thomas R., Wang W., Su D. M. (2020). Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging. Immun. Ageing 17, 2. 10.1186/s12979-020-0173-8 PubMed DOI PMC

Tidu F., De Zuani M., Jose S. S., Bendíčková K., Kubala L., Caruso F., et al. (2021). NFAT Signaling in Human Mesenchymal Stromal Cells Affects Extracellular Matrix Remodeling and Antifungal Immune Responses. iScience 24 (6), 102683. 10.1016/j.isci.2021.102683 PubMed DOI PMC

Timmerman K. L., Flynn M. G., Coen P. M., Markofski M. M., Pence B. D. (2008). Exercise Training-Induced Lowering of Inflammatory (CD14+CD16+) Monocytes: A Role in the Anti-inflammatory Influence of Exercise? J. Leukoc. Biol. 84 (5), 1271–1278. 10.1189/jlb.0408244 PubMed DOI

Todhunter M. E., Sayaman R. W., Miyano M., LaBarge M. A. (2018). Tissue Aging: The Integration of Collective and Variant Responses of Cells to Entropic Forces over Time. Curr. Opin. Cel Biol. 54, 121–129. 10.1016/j.ceb.2018.05.016 PubMed DOI PMC

Toft A. D., Jensen L. B., Bruunsgaard H., Ibfelt T., Halkjær-Kristensen J., Febbraio M., et al. (2002). Cytokine Response to Eccentric Exercise in Young and Elderly Humans. Am. J. Physiol. Cell Physiol. 283 (1), C289–C295. 10.1152/ajpcell.00583.2001 PubMed DOI

Toth M. J., Matthews D. E., Tracy R. P., Previs M. J. (2005). Age-related Differences in Skeletal Muscle Protein Synthesis: Relation to Markers of Immune Activation. Am. J. Physiol. Endocrinol. Metab. 288 (5), E883–E891. 10.1152/ajpendo.00353.2004 PubMed DOI

Valiathan R., Ashman M., Asthana D. (2016). Effects of Ageing on the Immune System: Infants to Elderly. Scand. J. Immunol. 83 (4), 255–266. 10.1111/sji.12413 PubMed DOI

Vallejo A. N., Schirmer M., Weyand C. M., Goronzy J. J. (2000). Clonality and Longevity of CD4+CD28null T Cells are Associated With Defects in Apoptotic Pathways. J. Immunol. 165 (11), 6301–6307. 10.4049/jimmunol.165.11.6301 PubMed DOI

van den Akker E. B., Pitts S. J., Deelen J., Moed M. H., Potluri S., van Rooij J., et al. (2016). Uncompromised 10-Year Survival of Oldest Old Carrying Somatic Mutations in DNMT3A and TET2. Blood 127 (11), 1512–1515. 10.1182/blood-2015-12-685925 PubMed DOI PMC

van Kalsbeek R. J., van der Pal H. J. H., Hjorth L., Winther J. F., Michel G., Haupt R., et al. (2021). The European Multistakeholder PanCareFollowUp Project: Novel, Person-Centred Survivorship Care to Improve Care Quality, Effectiveness, Cost-Effectiveness and Accessibility for Cancer Survivors and Caregivers. Eur. J. Cancer 153, 74–85. 10.1016/j.ejca.2021.05.030 PubMed DOI

Vatanen A., Hou M., Huang T., Söder O., Jahnukainen T., Kurimo M., et al. (2017). Clinical and Biological Markers of Premature Aging After Autologous SCT in Childhood Cancer. Bone Marrow Transpl. 52 (4), 600–605. 10.1038/bmt.2016.334 PubMed DOI

Vaziri H., Dragowska W., Allsopp R. C., Thomas T. E., Harley C. B., Lansdorp P. M. (1994). Evidence for a Mitotic Clock in Human Hematopoietic Stem Cells: Loss of Telomeric DNA with Age. Proc. Natl. Acad. Sci. 91 (21), 9857–9860. 10.1073/pnas.91.21.9857 PubMed DOI PMC

Wallace W. H. B., Blacklay A., Eiser C., Davies H., Hawkins M., Levitt G. A., et al. (2001). Regular Review: Developing Strategies for Long Term Follow up of Survivors of Childhood Cancer. Bmj 323 (7307), 271–274. 10.1136/bmj.323.7307.271 PubMed DOI PMC

Wang E. C., Moss P. A., Frodsham P., Lehner P. J., Bell J. I., Borysiewicz L. K. (1995). CD8highCD57+ T Lymphocytes in Normal, Healthy Individuals are Oligoclonal and Respond to Human Cytomegalovirus. J. Immunol. 155 (10), 5046–5056. PubMed

Wang S., Prizment A., Thyagarajan B., Blaes A. (2021). Cancer Treatment-Induced Accelerated Aging in Cancer Survivors: Biology and Assessment. Cancers 13 (3), 427. 10.3390/cancers13030427 PubMed DOI PMC

Wang X., Lu Y., Li C., Larbi A., Feng L., Shen Q., et al. (2020). Associations of Lifestyle Activities and a Heathy Diet With Frailty in Old Age: A Community-Based Study in Singapore. Aging 12 (1), 288–308. 10.18632/aging.102615 PubMed DOI PMC

Weidner C., Lin Q., Koch C., Eisele L., Beier F., Ziegler P., et al. (2014). Aging of Blood Can be Tracked by DNA Methylation Changes at Just Three CpG Sites. Genome Biol. 15 (2), R24. 10.1186/gb-2014-15-2-r24 PubMed DOI PMC

Weng N.-p., Akbar A. N., Goronzy J. (2009). CD28− T Cells: Their Role in the Age-Associated Decline of Immune Function. Trends Immunol. 30 (7), 306–312. 10.1016/j.it.2009.03.013 PubMed DOI PMC

Wenisch C., Patruta S., Daxböck F., Krause R., Hörl W. (2000). Effect of Age on Human Neutrophil Function. J. Leukoc. Biol. 67 (1), 40–45. 10.1002/jlb.67.1.40 PubMed DOI

Weyh C., Kruger K., Strasser B. (2020). Physical Activity and Diet Shape the Immune System During Aging. Nutrients 12 (3). 10.3390/nu12030622 PubMed DOI PMC

Wherry E. J. (2011). T Cell Exhaustion. Nat. Immunol. 12 (6), 492–499. 10.1038/ni.2035 PubMed DOI

White M. J., Nielsen C. M., McGregor R. H. C., Riley E. M., Goodier M. R. (2014). Differential Activation of CD 57‐Defined Natural Killer Cell Subsets During Recall Responses to Vaccine Antigens. Immunology 142 (1), 140–150. 10.1111/imm.12239 PubMed DOI PMC

Wiley C. D., Campisi J. (2016). From Ancient Pathways to Aging Cells-Connecting Metabolism and Cellular Senescence. Cell Metab. 23 (6), 1013–1021. 10.1016/j.cmet.2016.05.010 PubMed DOI PMC

Wilson C. L., Liu W., Yang J. J., Kang G., Ojha R. P., Neale G. A., et al. (2015). Genetic and Clinical Factors Associated With Obesity Among Adult Survivors of Childhood Cancer: A Report From the St. Jude Lifetime Cohort. Cancer 121 (13), 2262–2270. 10.1002/cncr.29153 PubMed DOI PMC

Wolff J. L., Starfield B., Anderson G. (2002). Prevalence, Expenditures, and Complications of Multiple Chronic Conditions in the Elderly. Arch. Intern. Med. 162 (20), 2269–2276. 10.1001/archinte.162.20.2269 PubMed DOI

Wong Y. T., Gruber J., Jenner A. M., Tay F. E. H., Ruan R. (2011). Chronic Resveratrol Intake Reverses Pro-inflammatory Cytokine Profile and Oxidative DNA Damage in Ageing Hybrid Mice. Age 33 (3), 229–246. 10.1007/s11357-010-9174-4 PubMed DOI PMC

Woo J., Yu R., Tang N., Leung J. (2014). Telomere Length is Associated with Decline in Grip Strength in Older Persons Aged 65 Years and over. Age 36 (5), 9711. 10.1007/s11357-014-9711-7 PubMed DOI PMC

Wood W. A., Krishnamurthy J., Mitin N., Torrice C., Parker J. S., Snavely A. C., et al. (2016). Chemotherapy and Stem Cell Transplantation Increase p16 INK4a Expression, a Biomarker of T-Cell Aging. EBioMedicine 11, 227–238. 10.1016/j.ebiom.2016.08.029 PubMed DOI PMC

Woodmansey E. J., McMurdo M. E. T., Macfarlane G. T., Macfarlane S. (2004). Comparison of Compositions and Metabolic Activities of Fecal Microbiotas in Young Adults and in Antibiotic-Treated and Non-antibiotic-treated Elderly Subjects. Appl. Environ. Microbiol. 70 (10), 6113–6122. 10.1128/aem.70.10.6113-6122.2004 PubMed DOI PMC

Wyczalkowska-Tomasik A., Czarkowska-Paczek B., Zielenkiewicz M., Paczek L. (2016). Inflammatory Markers Change with Age, But do Not Fall Beyond Reported Normal Ranges. Arch. Immunol. Ther. Exp. 64 (3), 249–254. 10.1007/s00005-015-0357-7 PubMed DOI PMC

Wynn R. F., Cross M. A., Hatton C., Will A. M., Lashford L. S., Dexter T. M., et al. (1998). Accelerated Telomere Shortening in Young Recipients of Allogeneic Bone-Marrow Transplants. Lancet 351 (9097), 178–181. 10.1016/s0140-6736(97)08256-1 PubMed DOI

Wynn R., Thornley I., Freedman M., Saunders E. F. (1999). Telomere Shortening in Leucocyte Subsets of Long-Term Survivors of Allogeneic Bone Marrow Transplantation. Br. J. Haematol. 105 (4), 997–1001. 10.1046/j.1365-2141.1999.01450.x PubMed DOI

Xu C., Zhu H., Qiu P. (2019). Aging Progression of Human Gut Microbiota. BMC Microbiol. 19 (1), 236. 10.1186/s12866-019-1616-2 PubMed DOI PMC

Xu W., Larbi A. (2017). Markers of T Cell Senescence in Humans. Int. J. Mol. Sci. 18 (8), 1742. 10.3390/ijms18081742 PubMed DOI PMC

Yalon M., Toren A., Jabarin D., Fadida E., Constantini S., Mehrian-Shai R. (2019). Elevated NLR May be a Feature of Pediatric Brain Cancer Patients. Front. Oncol. 9, 327. 10.3389/fonc.2019.00327 PubMed DOI PMC

Yousefzadeh M. J., Flores R. R., Zhu Y., Schmiechen Z. C., Brooks R. W., Trussoni C. E., et al. (2021). An Aged Immune System Drives Senescence and Ageing of Solid Organs. Nature 594 (7861), 100–105. 10.1038/s41586-021-03547-7 PubMed DOI PMC

Zanni F., Vescovini R., Biasini C., Fagnoni F., Zanlari L., Telera A., et al. (2003). Marked Increase With Age of Type 1 Cytokines Within Memory and Effector/Cytotoxic CD8+ T Cells in Humans: A Contribution to Understand the Relationship Between Inflammation and Immunosenescence. Exp. Gerontol. 38 (9), 981–987. 10.1016/s0531-5565(03)00160-8 PubMed DOI

Zhang J., Wang X., Vikash V., Ye Q., Wu D., Liu Y., et al. (2016). ROS and ROS-Mediated Cellular Signaling. Oxid. Med. Cell. Longev. 2016, 4350965. 10.1155/2016/4350965 PubMed DOI PMC

Zhao J., Miao K., Wang H., Ding H., Wang D. W. (2013). Association Between Telomere Length and Type 2 Diabetes Mellitus: A Meta-Analysis. PLoS One 8 (11), e79993. 10.1371/journal.pone.0079993 PubMed DOI PMC

Zhao K., Liu Q. (2016). The Clinical Application of Mesenchymal Stromal Cells in Hematopoietic Stem Cell Transplantation. J. Hematol. Oncol. 9 (1), 46. 10.1186/s13045-016-0276-z PubMed DOI PMC

Zink F., Stacey S. N., Norddahl G. L., Frigge M. L., Magnusson O. T., Jonsdottir I., et al. (2017). Clonal Hematopoiesis, With and Without Candidate Driver Mutations, is Common in the Elderly. Blood 130 (6), 742–752. 10.1182/blood-2017-02-769869 PubMed DOI PMC