Can blocking inflammation enhance immunity during aging?

被引：62

作者：

Chambers, Emma S. ^{[1
,2
]}

Akbar, Arne N. ^{[1
]}

机构：

[1] UCL, Div Infect & Immun, London, England

[2] Queen Mary Univ London, Blizard Inst, Ctr Immunobiol, 4 Newark St, London E1 2AT, England

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2020年 / 145卷 / 05期

基金：

英国医学研究理事会;

关键词：

Inflammaging; senescence; p38-MAP Kinase; senolytics; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; T-CELL RESPONSES; SENESCENT CELLS; SECRETORY PHENOTYPE; MICROBIOTA COMPOSITION; SYSTEMIC INFLAMMATION; COGNITIVE DECLINE; IN-VIVO; EXPRESSION;

D O I：

10.1016/j.jaci.2020.03.016

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Aging is a global burden, and the increase in life span does not increase in parallel with health span. Therefore, older adults are currently living longer with chronic diseases, increased infections, and cancer. A characteristic of aging is the presence of chronic low-grade inflammation that is characterized by elevated concentrations of IL-6, TNF-alpha, and C-reactive protein, which has been termed inflammaging. Previous studies have demonstrated that chronic inflammation interferes with T-cell response and macrophage function and is also detrimental for vaccine responses. This raises the question of whether therapeutic strategies that reduce inflammation may be useful for improving immunity in older adults. In this review we discuss the potential causes of inflammaging, the cellular source of the inflammatory mediators, and the mechanisms by which inflammation may inhibit immunity. Finally, we describe existing interventions that target inflammation that have been used to enhance immunity during aging.

引用

页码：1323 / 1331

页数：9

共 107 条

[1] A complex secretory program orchestrated by the inflammasome controls paracrine senescence [J].

Acosta, Juan Carlos ;

Banito, Ana ;

Wuestefeld, Torsten ;

Georgilis, Athena ;

Janich, Peggy ;

Morton, Jennifer P. ;

Athineos, Dimitris ;

Kang, Tae-Won ;

Lasitschka, Felix ;

Andrulis, Mindaugas ;

Pascual, Gloria ;

Morris, Kelly J. ;

Khan, Sadaf ;

Jin, Hong ;

Dharmalingam, Gopuraja ;

Snijders, Ambrosius P. ;

Carroll, Thomas ;

Capper, David ;

Pritchard, Catrin ;

Inman, Gareth J. ;

Longerich, Thomas ;

Sansom, Owen J. ;

Aznar Benitah, Salvador ;

Zender, Lars ;

Gil, Jesus .

NATURE CELL BIOLOGY, 2013, 15 (08) :978-U221

[2] Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging [J].

Agius, Elaine ;

Lacy, Katie E. ;

Vukmanovic-Stejic, Milica ;

Jagger, Ann L. ;

Papageorgiou, Anna-Pia ;

Hall, Sue ;

Reed, John R. ;

Curnow, S. John ;

Fuentes-Duculan, Judilyn ;

Buckley, Christopher D. ;

Salmon, Mike ;

Taams, Leonie S. ;

Krueger, James ;

Greenwood, John ;

Klein, Nigel ;

Rustin, Malcolm H. A. ;

Akbar, Arne N. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (09) :1929-1940

[3] Investigation of the cutaneous response to recall antigen in humans in vivo [J].

Akbar, A. N. ;

Reed, J. R. ;

Lacy, K. E. ;

Jackson, S. E. ;

Vukmanovic-Stejic, M. ;

Rustin, M. H. A. .

CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2013, 173 (02) :163-172

[4] Senescence of T Lymphocytes: Implications for Enhancing Human Immunity [J].

Akbar, Arne N. ;

Henson, Sian M. ;

Lanna, Alessio .

TRENDS IN IMMUNOLOGY, 2016, 37 (12) :866-876

[5] Suppression of the senescence-associated secretory phenotype (SASP) in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK2 [J].

Alimbetov, Dauren ;

Davis, Terence ;

Brook, Amy J. C. ;

Cox, Lynne S. ;

Faragher, Richard G. A. ;

Nurgozhin, Talgat ;

Zhumadilov, Zhaxybay ;

Kipling, David .

BIOGERONTOLOGY, 2016, 17 (02) :305-315

[6] Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells [J].

Andre, Pascale ;

Denis, Caroline ;

Soulas, Caroline ;

Bourbon-Caillet, Clarisse ;

Lopez, Julie ;

Arnoux, Thomas ;

Blery, Mathieu ;

Bonnafous, Cecile ;

Gauthier, Laurent ;

Morel, Ariane ;

Rossi, Benjamin ;

Remark, Romain ;

Breso, Violette ;

Bonnet, Elodie ;

Habif, Guillaume ;

Guia, Sophie ;

Lalanne, Ana Ines ;

Hoffmann, Caroline ;

Lantz, Olivier ;

Fayette, Jerome ;

Boyer-Chammard, Agnes ;

Zerbib, Robert ;

Dodion, Pierre ;

Ghadially, Hormas ;

Jure-Kunkel, Maria ;

Morel, Yannis ;

Herbst, Ronald ;

Narni-Mancinelli, Emilie ;

Cohen, Roger B. ;

Vivier, Eric .

CELL, 2018, 175 (07) :1731-+

[7] Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians [J].

Arai, Yasumichi ;

Martin-Ruiz, Carmen M. ;

Takayama, Michiyo ;

Abe, Yukiko ;

Takebayashi, Toru ;

Koyasu, Shigeo ;

Suematsu, Makoto ;

Hirose, Nobuyoshi ;

von Zglinicki, Thomas .

EBIOMEDICINE, 2015, 2 (10) :1549-1558

[8] Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging [J].

Baar, Marjolein P. ;

Brandt, Renata M. C. ;

Putavet, Diana A. ;

Klein, Julian D. D. ;

Derks, Kasper W. J. ;

Bourgeois, Benjamin R. M. ;

Stryeck, Sarah ;

Rijksen, Yvonne ;

van Willigenburg, Hester ;

Feijtel, Danny A. ;

van der Pluijm, Ingrid ;

Essers, Jeroen ;

van Cappellen, Wiggert A. ;

van IJcken, Wilfred F. ;

Houtsmuller, Adriaan B. ;

Pothof, Joris ;

de Bruin, Ron W. F. ;

Madl, Tobias ;

Hoeijmakers, Jan H. J. ;

Campisi, Judith ;

de Keizer, Peter L. J. .

CELL, 2017, 169 (01) :132-+

[9] Naturally occurring p16Ink4a-positive cells shorten healthy lifespan [J].

Baker, Darren J. ;

Childs, Bennett G. ;

Durik, Matej ;

Wijers, Melinde E. ;

Sieben, Cynthia J. ;

Zhong, Jian ;

Saltness, Rachel A. ;

Jeganathan, Karthik B. ;

Verzosa, Grace Casaclang ;

Pezeshki, Abdulmohammad ;

Khazaie, Khashayarsha ;

Miller, Jordan D. ;

van Deursen, Jan M. .

NATURE, 2016, 530 (7589) :184-+

[10] Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders [J].

Baker, Darren J. ;

Wijshake, Tobias ;

Tchkonia, Tamar ;

LeBrasseur, Nathan K. ;

Childs, Bennett G. ;

van de Sluis, Bart ;

Kirkland, James L. ;

van Deursen, Jan M. .

NATURE, 2011, 479 (7372) :232-U112

← 1 2 3 4 5 6 7 8 9 10 →