Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Jun 3:9:172.
doi: 10.3389/fnins.2015.00172. eCollection 2015.

Immune aging, dysmetabolism, and inflammation in neurological diseases

Michela Deleidi  1 , Madeline Jäggle  1 , Graziella Rubino  2
Affiliations
Review

Immune aging, dysmetabolism, and inflammation in neurological diseases

Michela Deleidi et al. Front Neurosci. .

Abstract

As we age, the immune system undergoes a process of senescence accompanied by the increased production of proinflammatory cytokines, a chronic subclinical condition named as "inflammaging". Emerging evidence from human and experimental models suggest that immune senescence also affects the central nervous system and promotes neuronal dysfunction, especially within susceptible neuronal populations. In this review we discuss the potential role of immune aging, inflammation and metabolic derangement in neurological diseases. The discovery of novel therapeutic strategies targeting age-linked inflammation may promote healthy brain aging and the treatment of neurodegenerative as well as neuropsychiatric disorders.

Keywords: aging; brain-immune interactions; immunosenescence; inflammation; metabolism; neurodegenerative diseases; neuropsychiatric diseases.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Immune aging, dysmetabolism, and inflammation in neurological diseases . The aging of the immune system is accompanied by a progressive senescence of immune cells (immunosenescence) and a chronic proinflammatory environment characterized by increased levels of cytokines and adipokines (inflammaging). These immune molecules modulate neuronal function and prime microglial cells and vulnerable neuronal populations. With aging, microglial cells also become senescent, lose their neuroprotective function and become more prone to abnormal inflammatory activation. Amyloid deposition and pathogenetic forms of α-synuclein activate microglia with the subsequent release of proinflammatory mediators. Aged dysfunctional mitochondria play a fundamental role in immunosenescence and age-related inflammation by the production of ROS and DAMPs that activate the NLRP3 inflammasome and immune cells triggering inflammatory reactions. In turn, inflammatory mediators aggravate mitochondrial dysfunction. High immune risk profile, infections and metabolic syndrome promote abnormal inflammatory reactions that contribute to disease onset and progression.
See this image and copyright information in PMC

References

    1. Abu-Taha M., Rius C., Hermenegildo C., Noguera I., Cerda-Nicolas J. M., Issekutz A. C., et al. . (2009). Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losartan. J. Immunol. 183, 1393–1402. 10.4049/jimmunol.0803157 - DOI - PubMed
    1. Acosta J. C., O'Loghlen A., Banito A., Guijarro M. V., Augert A., Raguz S., et al. . (2008). Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018. 10.1016/j.cell.2008.03.038 - DOI - PubMed
    1. Alzheimer's Disease Anti-inflammatory Prevention Trial Research, G. (2013). Results of a follow-up study to the randomized Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT). Alzheimers Dement. 9, 714–723. 10.1016/j.jalz.2012.11.012 - DOI - PMC - PubMed
    1. Appay V., Dunbar P. R., Callan M., Klenerman P., Gillespie G. M., Papagno L., et al. . (2002). Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med. 8, 379–385. 10.1038/nm0402-379 - DOI - PubMed
    1. Appay V., Fastenackels S., Katlama C., Ait-Mohand H., Schneider L., Guihot A., et al. . (2011). Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients. AIDS 25, 1813–1822. 10.1097/QAD.0b013e32834640e6 - DOI - PubMed