Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

Zierer, 2015, Integration of ‘omics’ data in aging research: from biomarkers to systems biology, Aging Cell, 14, 933, 10.1111/acel.12386

Jazwinski, 2015, Aging and health – a systems biology perspective. introduction, Interdiscip Top Gerontol, 40, VII

Cohen, 2016, Complex systems dynamics in aging: new evidence, continuing questions, Biogerontology, 17, 205, 10.1007/s10522-015-9584-x

Fulop, 2015, Frailty, inflammation and immunosenescence, Interdiscip Top Gerontol Geriatr, 41, 26, 10.1159/000381134

Pawelec, 2017, Does the human immune system ever really become “senescent”?, F1000Res, 6, 1323, 10.12688/f1000research.11297.1

Franceschi, 2017, Immunobiography and the heterogeneity of immune responses in the elderly: a focus on inflammaging and trained immunity, Front Immunol, 8, 982, 10.3389/fimmu.2017.00982

Xu, 2017, Markers of T cell senescence in humans, Int J Mol Sci, 18, E1742, 10.3390/ijms18081742

Fulop, 2016, From inflamm-aging to immune-paralysis: a slippery slope during aging for immune-adaptation, Biogerontology, 17, 147, 10.1007/s10522-015-9615-7

Goronzy, 2015, Naïve T cell maintenance and function in human ageing, J Immunol, 194, 4073, 10.4049/jimmunol.1500046

Pawelec, 2012, Hallmarks of human “immunosenescence”: adaptation or dysregulation?, Immun Ageing, 9, 15, 10.1186/1742-4933-9-15

Yanes, 2017, Lymphocyte generation and population homeostasis throughout life, Semin Hematol, 54, 33, 10.1053/j.seminhematol.2016.10.003

Solana, 2012, Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans, Semin Immunol, 24, 331, 10.1016/j.smim.2012.04.008

Montgomery, 2015, Paradoxical changes in innate immunity in aging: recent progress and new directions, J Leukoc Biol, 98, 937, 10.1189/jlb.5MR0315-104R

Fülöp, 1985, Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes, Clin Exp Immunol, 61, 425

Franceschi, 2000, Inflamm-aging. An evolutionary perspective on immunosenescence, Ann N Y Acad Sci, 908, 244, 10.1111/j.1749-6632.2000.tb06651.x

Müller, 2013, Immunosenescence in vertebrates and invertebrates, Immun Ageing, 10, 12, 10.1186/1742-4933-10-12

Rivera, 2016, Innate cell communication kick-starts pathogen-specific immunity, Nat Immunol, 17, 356, 10.1038/ni.3375

Kaufmann, 2016, Molecular determinants in phagocyte-bacteria interactions, Immunity, 44, 476, 10.1016/j.immuni.2016.02.014

Vidya, 2017, Toll-like receptors: significance, ligands, signaling pathways, and functions in mammals, Int Rev Immunol, 13, 1, 10.1080/08830185.2017.1380200

Kufer, 2016, Multifaceted functions of NOD-like receptor proteins in myeloid cells at the intersection of innate and adaptive immunity, Microbiol Spectr, 4, 429, 10.1128/microbiolspec.MCHD-0021-2015

Barik, 2016, What really rigs up RIG-I?, J Innate Immun, 8, 429, 10.1159/000447947

Kleinnijenhuis, 2012, Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes, Proc Natl Acad Sci U S A, 109, 17537, 10.1073/pnas.1202870109

Netea, 2017, Trained immunity: an ancient way of remembering, Cell Host Microbe, 21, 297, 10.1016/j.chom.2017.02.003

Tieri, 2010, Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system, Theor Biol Med Model, 11, 32, 10.1186/1742-4682-7-32

Bektas, 2017, Human T cell immunosenescence and inflammation in aging, J Leukoc Biol, 102, 977, 10.1189/jlb.3RI0716-335R

Molony, 2017, Reduced dynamic range of antiviral innate immune responses in aging, Exp Gerontol, 30483, 10.1016/j.exger.2017.08.019

Byun, 2015, From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes, BMB Rep, 48, 549, 10.5483/BMBRep.2015.48.10.122

Biagi, 2012, Aging of the human metaorganism: the microbial counterpart, Age (Dordr), 34, 247, 10.1007/s11357-011-9217-5

Bauer, 2016, The role of oxidative and inflammatory stress and persistent viral infections in immunosenescence, Mech Ageing Dev, 158, 27, 10.1016/j.mad.2016.01.001

Franceschi, 2017, Inflammaging and ‘Garb-aging’, Trends Endocrinol Metab, 28, 199, 10.1016/j.tem.2016.09.005

van der Heijden, 2017, Epigenetics and trained immunity, Antioxid Redox Signal, 10.1089/ars.2017.7310

Bekkering, 2016, In vitro experimental model of trained innate immunity in human primary monocytes, Clin Vaccine Immunol, 23, 926, 10.1128/CVI.00349-16

Calabrese, 2015, What is hormesis and its relevance to healthy aging and longevity?, Biogerontology, 16, 693, 10.1007/s10522-015-9601-0

Martucci, 2017, Mediterranean diet and inflammaging within the hormesis paradigm, Nutr Rev, 75, 442, 10.1093/nutrit/nux013

Ostan, 2008, Immunosenescence and immunogenetics of human longevity, Neuroimmunomodulation, 15, 224, 10.1159/000156466

Arai, 2015, Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians, EBioMedicine, 2, 1549, 10.1016/j.ebiom.2015.07.029

Lowe, 2016, Epigenetic clock analyses of cellular senescence and ageing, Oncotarget, 7, 8524, 10.18632/oncotarget.7383

Garagnani, 2012, Methylation of ELOVL2 gene as a new epigenetic marker of age, Aging Cell, 11, 1132, 10.1111/acel.12005

Horvath, 2015, Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring, Aging (Albany NY)., 7, 1159, 10.18632/aging.100861

Franceschi, 2007, Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans, Mech Ageing Dev, 128, 92, 10.1016/j.mad.2006.11.016

Morrisette-Thomas, 2014, Inflamm-aging does not simply reflect increases in pro-inflammatory markers, Mech Ageing Dev, 139, 49, 10.1016/j.mad.2014.06.005

Monti, 2017, Inflammaging and human longevity in the omics era, Mech Ageing Dev, 165, 129, 10.1016/j.mad.2016.12.008

Fülöp, 2016, The role of immunosenescence in the development of age-related diseases, Rev Invest Clin, 68, 84

Geeraerts, 2017, Macrophage metabolism as therapeutic target for cancer, atherosclerosis, and obesity, Front Immunol, 15, 289, 10.3389/fimmu.2017.00289

Rose, 2017, Mitochondria and mitochondria-induced signalling molecules as longevity determinants, Mech Ageing Dev, 165, 115, 10.1016/j.mad.2016.12.002

Calabrese, 2017, Aging and Parkinson’s disease: inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis, Free Radic Biol Med, 115, 80, 10.1016/j.freeradbiomed.2017.10.379

Agrawal, 2017, Role of dendritic cells in inflammation and loss of tolerance in the elderly, Front Immunol, 8, 896, 10.3389/fimmu.2017.00896

Johnston-Carey, 2015, The immunoproteasome in oxidative stress, aging, and disease, Crit Rev Biochem Mol Biol, 51, 268, 10.3109/10409238.2016.1172554

Fulop, 2014, Cellular signaling in the aging immune system, Curr Opin Immunol, 29, 105, 10.1016/j.coi.2014.05.007

Bryl, 2004, Decreased proliferative capability of CD4+ cells of elderly people is associated with faster loss of activation-related antigens and accumulation of regulatory T cells, Exp Gerontol, 39, 587, 10.1016/j.exger.2003.10.029

Rider, 2003, Oxidative inactivation of CD45 protein tyrosine phosphatase may contribute to T lymphocyte dysfunction in the elderly, Mech Ageing Dev, 124, 191, 10.1016/S0047-6374(02)00120-3

Das, 2017, Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3, PLoS One, 12, e0185932, 10.1371/journal.pone.0185932

Mittrücker, 2014, Heterogeneity in the differentiation and function of CD8? T cells, Arch Immunol Ther Exp (Warsz), 62, 449, 10.1007/s00005-014-0293-y

Golubovskaya, 2016, Different subsets of T cells, memory, effector functions, and CAR-T Immunotherapy, Cancers (Basel), 8, E36, 10.3390/cancers8030036

Larbi, 2014, From “truly naïve” to “exhausted senescent” T cells: when markers predict functionality, Cytometry A, 85, 25, 10.1002/cyto.a.22351

Kim, 2017, The life cycle of a T cell after vaccination – where does immune ageing strike?, Clin Exp Immunol, 187, 71, 10.1111/cei.12829

Tu, 2016, Mechanisms underlying T cell immunosenescence: aging and Cytomegalovirus infection, Front Microbiol, 7, 2111, 10.3389/fmicb.2016.02111

Appay, 2014, Naive T cells: the crux of cellular immune aging?, Exp Gerontol, 54, 90, 10.1016/j.exger.2014.01.003

Nguyen, 2017, Perturbed CD8+ T cell immunity across universal influenza epitopes in the elderly, J Leukoc Biol, 10.1189/jlb.5MA0517-207R

Pawelec, 2017, Immunosenescence and cancer, Biogerontology, 18, 717, 10.1007/s10522-017-9682-z

Gattinoni, 2017, T memory stem cells in health and disease, Nat Med, 23, 18, 10.1038/nm.4241

Pawelec, 2014, Immunosenenescence: role of cytomegalovirus, Exp Gerontol, 54, 1, 10.1016/j.exger.2013.11.010

Derhovanessian, 2013, Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people, Age (Dordr), 35, 1387, 10.1007/s11357-012-9425-7

Solana, 2012, CMV and immunosenescence: from basics to clinics, Immun Ageing, 9, 23, 10.1186/1742-4933-9-23

Pawelec, 2012, The impact of CMV infection on survival in older humans, Curr Opin Immunol, 24, 507, 10.1016/j.coi.2012.04.002

Söderberg-Nauclér, 2016, Cytomegalovirus driven immunosenescence-an immune phenotype with or without clinical impact?, Mech Ageing Dev, 158, 3, 10.1016/j.mad.2016.06.005

McElhaney, 2015, Predictors of the antibody response to influenza vaccination in older adults with type 2 diabetes, BMJ Open Diabetes Res Care, 3, e000140, 10.1136/bmjdrc-2015-000140

Bajwa, 2017, CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival, J Infect Dis, 215, 1212, 10.1093/infdis/jix080

Campisi, 2014, Cell senescence: role in aging and age-related diseases, Interdiscip Top Gerontol, 39, 45, 10.1159/000358899

Effros, 2003, Replicative senescence: the final stage of memory T cell differentiation?, Curr HIV Res, 1, 153, 10.2174/1570162033485348

Coppé, 2008, Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor, PLoS Biol, 6, 2853, 10.1371/journal.pbio.0060301

Rao, 2016, SASP: tumor suppressor or promoter? Yes!, Trends Cancer, 2, 676, 10.1016/j.trecan.2016.10.001

Capece, 2017, Cancer secretome and inflammation: the bright and the dark sides of NF-κB, Semin Cell Dev Biol, 10.1016/j.semcdb.2017.08.004

Campisi, 2016, Cellular senescence and lung function during aging. Yin and Yang, Ann Am Thorac Soc, 13, S402, 10.1513/AnnalsATS.201609-703AW

Wherry, 2015, Molecular and cellular insights into T cell exhaustion, Nat Rev Immunol, 15, 486, 10.1038/nri3862

Akbar, 2016, Senescence of T lymphocytes: implications for enhancing human immunity, Trends Immunol, 37, 866, 10.1016/j.it.2016.09.002

Henson, 2015, Blockade of PD-1 or p38 MAP kinase signaling enhances senescent human CD8+ T-cell proliferation by distinct pathways, Eur J Immunol, 45, 1441, 10.1002/eji.201445312

Zou, 2016, PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations, Sci Transl Med, 8, 328rv324, 10.1126/scitranslmed.aad7118

Zarour, 2016, Reversing T-cell dysfunction and exhaustion in cancer, Clin Cancer Res, 22, 1856, 10.1158/1078-0432.CCR-15-1849

Elias, 2017, Immunotherapy comes of age: immune aging & checkpoint inhibitors, J Geriatr Oncol, 8, 229, 10.1016/j.jgo.2017.02.001

Daste, 2017, Immune checkpoint inhibitors and elderly people: a review, Eur J Cancer, 82, 155, 10.1016/j.ejca.2017.05.044

Hurez, 2017, Considerations for successful cancer immunotherapy in aged hosts, Clin Exp Immunol, 187, 53, 10.1111/cei.12875

MacIver, 2013, Metabolic regulation of T lymphocytes, Annu Rev Immunol, 31, 259, 10.1146/annurev-immunol-032712-095956

Michalek, 2010, The metabolic life and times of a T-cell, Immunol Rev, 236, 190, 10.1111/j.1600-065X.2010.00911.x

Kouidhi, 2017, Impact of metabolism on T-cell differentiation and function and cross talk with tumor microenvironment, Front Immunol, 8, 270, 10.3389/fimmu.2017.00270

Liu, 2014, Cellular metabolism modulation in T lymphocyte immunity, Immunology, 10.1111/imm.12321

Peng, 2016, Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism, Science, 354, 481, 10.1126/science.aaf6284

Buck, 2017, Metabolic instruction of immunity, Cell, 169, 570, 10.1016/j.cell.2017.04.004

Henson, 2014, p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+T cells, J Clin Invest, 124, 4004, 10.1172/JCI75051

Akbar, 2017, The convergence of senescence and nutrient sensing during lymphocyte ageing, Clin Exp Immunol, 187, 4, 10.1111/cei.12876

Weyand, 2016, Aging of the immune system. Mechanisms and therapeutic targets, Ann Am Thorac Soc, 13, S422, 10.1513/AnnalsATS.201602-095AW

Yu, 2012, Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age, Proc Natl Acad Sci U S A, 109, E879, 10.1073/pnas.1109797109

Li, 2012, Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity, Nat Med, 18, 1518, 10.1038/nm.2963

Chakraborty, 2014, Insights into the initiation of TCR signaling, Nat Immunol, 15, 798, 10.1038/ni.2940

Porciello, 2016, CD28 costimulatory signals in T lymphocyte activation: emerging functions beyond a qualitative and quantitative support to TCR signalling, Cytokine Growth Factor Rev, 28, 11, 10.1016/j.cytogfr.2016.02.004

Dustin, 2011, New insights into the T cell synapse from single molecule techniques, Nat Rev Immunol, 11, 672, 10.1038/nri3066

Larbi, 2006, Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging, Cell Signal, 18, 1017, 10.1016/j.cellsig.2005.08.016

Turner, 2017, Does regular exercise counter T cell immunosenescence reducing the risk of developing cancer and promoting successful treatment of malignancies?, Oxid Med Cell Longev, 2017, 4234765, 10.1155/2017/4234765

Weltevrede, 2016, Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: a systematic review, Exp Gerontol, 77, 87, 10.1016/j.exger.2016.02.005

Bartlett, 2012, The age-related increase in low-grade systemic inflammation (inflammaging) is not driven by cytomegalovirus infection, Aging Cell, 11, 912, 10.1111/j.1474-9726.2012.00849.x

van der Geest, 2014, Aging disturbs the balance between effector and regulatory CD4+ T cells, Exp Gerontol, 60, 190, 10.1016/j.exger.2014.11.005

Frasca, 2016, The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations, Vaccine, 34, 2834, 10.1016/j.vaccine.2016.04.023

Sonntag, 2016, GeroScience: understanding the interaction of processes of aging and chronic diseases, Age (Dordr), 38, 377, 10.1007/s11357-016-9953-7

Franceschi, 2016, Suggestions from geroscience for the genetics of age-related diseases, PLoS Genet, 12, e1006399, 10.1371/journal.pgen.1006399

Sierra, 2016, The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span, Cold Spring Harb Perspect Med, 6, a025163, 10.1101/cshperspect.a025163

Yang, 2012, Aging and cancer mortality: dynamics of change and sex differences, Exp Gerontol, 47, 695, 10.1016/j.exger.2012.06.009

Weinberger, 2013, Recall responses to tetanus and diphtheria vaccination are frequently insufficient in elderly persons, PLoS One, 8, e82967, 10.1371/journal.pone.0082967

Merani, 2017, Impact of aging and Cytomegalovirus on immunological response to influenza vaccination and infection, Front Immunol, 8, 784, 10.3389/fimmu.2017.00784

Haq, 2014, Immunosenescence: influenza vaccination and the elderly, Curr Opin Immunol, 29, 38, 10.1016/j.coi.2014.03.008

Lal, 2015, Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults, N Engl J Med, 372, 2087, 10.1056/NEJMoa1501184

Fulop, 2010, Aging, frailty and age-related diseases, Biogerontology, 11, 547, 10.1007/s10522-010-9287-2

Hurez, 2017, Considerations for successful cancer immunotherapy in aged hosts, Exp Gerontol, 10.1016/j.exger.2017.10.002

Sansoni, 2014, New advances in CMV and immunosenescence, Exp Gerontol, 55, 54, 10.1016/j.exger.2014.03.020

Santoro, 2017, Gut microbiota changes in the extreme decades of human life: a focus on centenarians, Cell Mol Life Sci, 10.1007/s00018-017-2674-y

Biagi, 2016, Gut microbiota and extreme longevity, Curr Biol, 26, 1480, 10.1016/j.cub.2016.04.016

Fried, 2001, Frailty in older adults evidence for a phenotype, J Gerontol A Biol Sci Med Sci, 56, M146, 10.1093/gerona/56.3.M146

Rockwood, 2007, A comparison of two approaches to measuring frailty in elderly people, J Gerontol A Biol Sci Med Sci, 62, 738, 10.1093/gerona/62.7.738

Wu, 2015, Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine, Biomedicine (Taipei), 5, 1, 10.7603/s40681-015-0001-1

Cohen, 2015, Detection of a novel, integrative aging process suggests complex physiological integration, PLoS One, 10, e0116489, 10.1371/journal.pone.0116489

Dusseault-Belanger, 2013, Validating metabolic syndrome through principal component analysis in a medically diverse, realistic cohort, Metab Syndr Relat Disord, 11, 21, 10.1089/met.2012.0094

Li, 2015, Homeostatic dysregulation proceeds in parallel in multiple physiological systems, Aging Cell, 14, 1103, 10.1111/acel.12402

Milot, 2014, Trajectories of physiological dysregulation predicts mortality and health outcomes in a consistent manner across three populations, Mech Ageing Dev, 14, 56, 10.1016/j.mad.2014.10.001

Arbeev, 2016, Optimal versus realized trajectories of physiological dysregulation in aging and their relation to sex-specific mortality risk, Front Public Health, 4, 3, 10.3389/fpubh.2016.00003

Szarc vel Szic, 2015, From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition?, Clin Epigenetics, 7, 33, 10.1186/s13148-015-0068-2

Quach, 2017, Epigenetic clock analysis of diet, exercise, education, and lifestyle factors, Aging (Albany NY), 9, 419, 10.18632/aging.101168

Campbell, 2017, Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis, Ageing Res Rev, 40, 31, 10.1016/j.arr.2017.08.003