The Aging Immune System: A Critical Attack on Ischemic Stroke

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2024 Sep 13

PMID 39271626

Authors

Wenzhe Xu

Yuying Guo

Linna Zhao

Rong Fu

Xiaoli Qin

Yunsha Zhang

Xueqi Cheng

Shixin Xu

Affiliations

Soon will be listed here.

Abstract

Ischemic stroke caused by cerebrovascular embolism is an age-related disease with high rates of disability and mortality. Although the mechanisms of immune and inflammatory development after stroke have been of great interest, most studies have neglected the critical and unavoidable factor of age. As the global aging trend intensifies, the number of stroke patients is constantly increasing, emphasizing the urgency of finding effective measures to address the needs of elderly stroke patients. The concept of "immunosenescence" appears to explain the worse stroke outcomes in older individuals. Immune remodeling due to aging involves dynamic changes at all levels of the immune system, and the overall consequences of central (brain-resident) and peripheral (non-brain-resident) immune cells in stroke vary according to the age of the individual. Lastly, the review outlines recent strategies aimed at immunosenescence to improve stroke prognosis.

References

Fan J, Li X, Yu X, Liu Z, Jiang Y, Fang Y . Global Burden, Risk Factor Analysis, and Prediction Study of Ischemic Stroke, 1990-2030. Neurology. 2023; 101(2):e137-e150. PMC: 10351546. DOI: 10.1212/WNL.0000000000207387. View

DeLong J, Ohashi S, OConnor K, Sansing L . Inflammatory Responses After Ischemic Stroke. Semin Immunopathol. 2022; 44(5):625-648. DOI: 10.1007/s00281-022-00943-7. View

Iadecola C, Buckwalter M, Anrather J . Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest. 2020; 130(6):2777-2788. PMC: 7260029. DOI: 10.1172/JCI135530. View

Faura J, Bustamante A, Miro-Mur F, Montaner J . Stroke-induced immunosuppression: implications for the prevention and prediction of post-stroke infections. J Neuroinflammation. 2021; 18(1):127. PMC: 8183083. DOI: 10.1186/s12974-021-02177-0. View

Zhao L, Xiao J, Li S, Guo Y, Fu R, Hua S . The interaction between intestinal microenvironment and stroke. CNS Neurosci Ther. 2023; 29 Suppl 1:185-199. PMC: 10314114. DOI: 10.1111/cns.14275. View

Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M . Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat Med. 2016; 22(5):516-23. PMC: 4860105. DOI: 10.1038/nm.4068. View

Fonarow G, Reeves M, Zhao X, Olson D, Smith E, Saver J . Age-related differences in characteristics, performance measures, treatment trends, and outcomes in patients with ischemic stroke. Circulation. 2010; 121(7):879-91. DOI: 10.1161/CIRCULATIONAHA.109.892497. View

Levine D, Wadley V, Langa K, Unverzagt F, Kabeto M, Giordani B . Risk Factors for Poststroke Cognitive Decline: The REGARDS Study (Reasons for Geographic and Racial Differences in Stroke). Stroke. 2018; 49(4):987-994. PMC: 6419761. DOI: 10.1161/STROKEAHA.117.018529. View

Lo J, Crawford J, Desmond D, Bae H, Lim J, Godefroy O . Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis. Stroke. 2021; 53(4):1318-1327. DOI: 10.1161/STROKEAHA.121.035796. View

10.

Ritzel R, Lai Y, Crapser J, Patel A, Schrecengost A, Grenier J . Aging alters the immunological response to ischemic stroke. Acta Neuropathol. 2018; 136(1):89-110. PMC: 6015099. DOI: 10.1007/s00401-018-1859-2. View

11.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . Hallmarks of aging: An expanding universe. Cell. 2023; 186(2):243-278. DOI: 10.1016/j.cell.2022.11.001. View

12.

Liu Z, Liang Q, Ren Y, Guo C, Ge X, Wang L . Immunosenescence: molecular mechanisms and diseases. Signal Transduct Target Ther. 2023; 8(1):200. PMC: 10182360. DOI: 10.1038/s41392-023-01451-2. View

13.

Rodrigues L, Teixeira V, Alencar-Silva T, Simonassi-Paiva B, Pereira R, Pogue R . Hallmarks of aging and immunosenescence: Connecting the dots. Cytokine Growth Factor Rev. 2021; 59:9-21. DOI: 10.1016/j.cytogfr.2021.01.006. View

14.

Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E . Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000; 908:244-54. DOI: 10.1111/j.1749-6632.2000.tb06651.x. View

15.

Fulop T, Larbi A, Dupuis G, Le Page A, Frost E, Cohen A . Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?. Front Immunol. 2018; 8:1960. PMC: 5767595. DOI: 10.3389/fimmu.2017.01960. View

16.

Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland J . Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013; 123(3):966-72. PMC: 3582125. DOI: 10.1172/JCI64098. View

17.

Carlos Acosta J, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton J . A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013; 15(8):978-90. PMC: 3732483. DOI: 10.1038/ncb2784. View

18.

da Silva P, Ogrodnik M, Kucheryavenko O, Glibert J, Miwa S, Cameron K . The bystander effect contributes to the accumulation of senescent cells in vivo. Aging Cell. 2018; 18(1):e12848. PMC: 6351849. DOI: 10.1111/acel.12848. View

19.

Santoro A, Bientinesi E, Monti D . Immunosenescence and inflammaging in the aging process: age-related diseases or longevity?. Ageing Res Rev. 2021; 71:101422. DOI: 10.1016/j.arr.2021.101422. View

20.

Dotson A, Zhu W, Libal N, Alkayed N, Offner H . Different immunological mechanisms govern protection from experimental stroke in young and older mice with recombinant TCR ligand therapy. Front Cell Neurosci. 2014; 8:284. PMC: 4174768. DOI: 10.3389/fncel.2014.00284. View