Targeting immune dysfunction in aging

被引:142
作者
Borgoni, Simone [1 ,2 ]
Kudryashova, Ksenia S. [1 ]
Burka, Ksenia [1 ]
de Magalhaes, Joao Pedro [1 ,3 ]
机构
[1] Centaura AG, Bleicherweg 10, CH-8002 Zurich, Switzerland
[2] Univ Zurich, Inst Expt Immunol, CH-8057 Zurich, Switzerland
[3] Univ Liverpool, Inst Ageing & Chron Dis, Integrat Genom Ageing Grp, Liverpool L7 8TX, Merseyside, England
关键词
Healthy longevity; Geroscience; Inflammation; Immune system; Anti-aging; Immunosenescence; HEMATOPOIETIC STEM-CELLS; RECOMBINANT HUMAN INTERLEUKIN-7; DENDRITIC CELLS; LIFE-SPAN; T-CELLS; CUTTING EDGE; CALORIE RESTRICTION; ALZHEIMERS-DISEASE; ADAPTIVE IMMUNITY; EPITHELIAL-CELLS;
D O I
10.1016/j.arr.2021.101410
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Human aging is a multifactorial phenomenon that affects numerous organ systems and cellular processes, with the immune system being one of the most dysregulated. Immunosenescence, the gradual deterioration of the immune system, and inflammaging, a chronic inflammatory state that persists in the elderly, are among the plethora of immune changes that occur during aging. Almost all populations of immune cells change with age in terms of numbers and/or activity. These alterations are in general highly detrimental, resulting in an increased susceptibility to infections, reduced healing abilities, and altered homeostasis that promote the emergence of age-associated diseases such as cancer, diabetes, and other diseases associated with inflammation. Thanks to recent developments, several strategies have been proposed to target central immunological processes or specific immune subpopulations affected by aging. These therapeutic approaches could soon be applied in the clinic to slow down or even reverse specific age-induced immune changes in order to rejuvenate the immune system and prevent or reduce the impact of various diseases. Due to its systemic nature and interconnection with all the other systems in the body, the immune system is an attractive target for aging intervention because relatively targeted modifications to a small set of cells have the potential to improve the health of multiple organ systems. Therefore, anti-aging immune targeting therapies could represent a potent approach for improving healthspan. Here, we review aging changes in the major components of the immune system, we summarize the current immune-targeting therapeutic approaches in the context of aging and discuss the future directions in the field of immune rejuvenation.
引用
收藏
页数:16
相关论文
共 225 条
[71]   A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing [J].
Florian, Maria Carolina ;
Nattamai, Kalpana J. ;
Doerr, Karin ;
Marka, Gina ;
Ueberle, Bettina ;
Vas, Virag ;
Eckl, Christina ;
Andrae, Immanuel ;
Schiemann, Matthias ;
Oostendorp, Robert A. J. ;
Scharffetter-Kochanek, Karin ;
Kestler, Hans Armin ;
Zheng, Yi ;
Geiger, Hartmut .
NATURE, 2013, 503 (7476) :392-+
[72]  
Franceschi C, 2000, ANN NY ACAD SCI, V908, P244
[73]   B Cells with a Senescent-Associated Secretory Phenotype Accumulate in the Adipose Tissue of Individuals with Obesity [J].
Frasca, Daniela ;
Romero, Maria ;
Diaz, Alain ;
Garcia, Denisse ;
Thaller, Seth ;
Blomberg, Bonnie B. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (04) :1-11
[74]   Precision medicine for cancer with next-generation functional diagnostics [J].
Friedman, Adam A. ;
Letai, Anthony ;
Fisher, David E. ;
Flaherty, Keith T. .
NATURE REVIEWS CANCER, 2015, 15 (12) :747-756
[75]   Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer's Disease Not Evident in Mouse Models [J].
Friedman, Brad A. ;
Srinivasan, Karpagam ;
Ayalon, Gai ;
Meilandt, William J. ;
Lin, Han ;
Huntley, Melanie A. ;
Cao, Yi ;
Lee, Seung-Hye ;
Haddick, Patrick C. G. ;
Ngu, Hai ;
Modrusan, Zora ;
Larson, Jessica L. ;
Kaminker, Joshua S. ;
van der Brug, Marcel P. ;
Hansen, David V. .
CELL REPORTS, 2018, 22 (03) :832-847
[76]   Aged marrow macrophages expand platelet-biased hematopoietic stem cells via interleukin-1B [J].
Frisch, Benjamin J. ;
Hoffman, Corey M. ;
Latchney, Sarah E. ;
LaMere, Mark W. ;
Myers, Jason ;
Ashton, John ;
Li, Allison J. ;
Saunders, Jerry, II ;
Palis, James ;
Perkins, Archibald S. ;
McCabe, Amanda ;
Smith, Julianne N. P. ;
McGrath, Kathleen E. ;
Rivera-Escalera, Fatima ;
McDavid, Andrew ;
Liesveld, Jane L. ;
Korshunov, Vyacheslav A. ;
Elliott, Michael R. ;
MacNamara, Katherine C. ;
Becker, Michael W. ;
Calvi, Laura M. .
JCI INSIGHT, 2019, 4 (10)
[77]   The many faces of IL-7: From lymphopoiesis to peripheral T cell maintenance [J].
Fry, TJ ;
Mackall, CL .
JOURNAL OF IMMUNOLOGY, 2005, 174 (11) :6571-6576
[78]   Identification of HSP90 inhibitors as a novel class of senolytics [J].
Fuhrmann-Stroissnigg, Heike ;
Ling, Yuan Yuan ;
Zhao, Jing ;
McGowan, Sara J. ;
Zhu, Yi ;
Brooks, Robert W. ;
Grassi, Diego ;
Gregg, Siobhan Q. ;
Stripay, Jennifer L. ;
Dorronsoro, Akaitz ;
Corbo, Lana ;
Tang, Priscilla ;
Bukata, Christina ;
Ring, Nadja ;
Giacca, Mauro ;
Li, Xuesen ;
Tchkonia, Tamara ;
Kirkland, James L. ;
Niedernhofer, Laura J. ;
Robbins, Paul D. .
NATURE COMMUNICATIONS, 2017, 8
[79]   Signal transduction and functional changes in neutrophils with aging [J].
Fulop, T ;
Larbi, A ;
Douziech, N ;
Fortin, C ;
Guérard, KP ;
Lesur, O ;
Khalil, A ;
Dupuis, G .
AGING CELL, 2004, 3 (04) :217-226
[80]   Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes? [J].
Fulop, Tamas ;
Larbi, Anis ;
Dupuis, Gilles ;
Le Page, Aurelie ;
Frost, Eric H. ;
Cohen, Alan A. ;
Witkowski, Jacek M. ;
Franceschi, Claudio .
FRONTIERS IN IMMUNOLOGY, 2018, 8