Immune aging, dysmetabolism, and inflammation in neurological diseases.

Published on Jun 3, 2015in Frontiers in Neuroscience3.648
· DOI :10.3389/fnins.2015.00172
Michela Deleidi10
Estimated H-index: 10
(German Center for Neurodegenerative Diseases),
Madeline Jäggle1
Estimated H-index: 1
(German Center for Neurodegenerative Diseases),
Graziella Rubino3
Estimated H-index: 3
(University of Tübingen)
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 ageing, inflammation and metabolic derangements 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.
  • References (241)
  • Citations (83)
📖 Papers frequently viewed together
1,958 Citations
1,095 Citations
913 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Shankar J. Chinta (Buck Institute for Research on Aging)H-Index: 25
#2Georgia Woods (Buck Institute for Research on Aging)H-Index: 2
Last. Julie K. Andersen (Buck Institute for Research on Aging)H-Index: 48
view all 6 authors...
Abstract Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex ‘senescence-associated secretory phenotype’ (SASP). The SASP includes many pro-inflammatory cytokines, chemokines, growth factors and proteases that have the potential to cause or exacerbate age-related pathology, both degenerative a...
77 CitationsSource
#1Lakshmi Narayanan Kota (National Institute of Mental Health and Neurosciences)H-Index: 5
#2Meera Purushottam (National Institute of Mental Health and Neurosciences)H-Index: 14
Last. Sanjeev Jain (National Institute of Mental Health and Neurosciences)H-Index: 24
view all 4 authors...
Aim Telomere attrition has been noted in many neuropsychiatric and neurodegenerative syndromes, and may indicate a shared molecular pathology across conditions. We evaluated telomere length in subjects with remitted and unremitted schizophrenia and in control subjects. Methods We measured telomere length as relative telomere/single-copy gene ratios in subjects with schizophrenia (n = 71) using quantitative real-time polymerase chain reaction. This was compared with relative telomere/single-copy ...
24 CitationsSource
#1Henrik HagbergH-Index: 87
#2Carina MallardH-Index: 51
Last. Pierre GressensH-Index: 67
view all 7 authors...
Neuroinflammation during critical phases of brain development can increase the risk of neurological and neuropsychiatric disorders, even in adulthood. In this Review, Hagberg et al. review the mechanisms through which inflammation can exacerbate perinatal brain injury, and outline how understanding the interplay between inflammation and brain injury can aid the identification of new strategies to alleviate neurological and neuropsychiatric morbidity.
260 CitationsSource
#1Yun-Hee Youm (Yale University)H-Index: 22
#2Kim Y. Nguyen (Yale University)H-Index: 7
Last. Vishwa Deep Dixit (Yale University)H-Index: 28
view all 17 authors...
Ketone bodies are elevated in response to fasting, a low-carbohydrate ketogenic diet or high-intensity exercise. Vishwa Deep Dixit and colleagues report that one metabolite, β-hydroxybutyrate, inhibits the NLRP3 inflammasome. In vivo, β-hydroxybutyrate is anti-inflammatory and suppresses NLRP3-mediated inflammatory disease.
403 CitationsSource
#1Lazaros Belbasis (UoI: University of Ioannina)H-Index: 12
#2Vanesa Bellou (UoI: University of Ioannina)H-Index: 6
Last. Ioanna Tzoulaki (Imperial College London)H-Index: 52
view all 5 authors...
Summary Background The cause of multiple sclerosis is believed to involve environmental exposure and genetic susceptibility. We aimed to summarise the environmental risk factors that have been studied in relation to onset of multiple sclerosis, assess whether there is evidence for diverse biases in this literature, and identify risk factors without evidence of biases. Methods We searched PubMed from inception to Nov 22, 2014, to identify systematic reviews and meta-analyses of observational stud...
189 CitationsSource
#1Luigi Fontana (MPG: Max Planck Society)H-Index: 51
#2Linda Partridge (MPG: Max Planck Society)H-Index: 101
Reduced food intake, avoiding malnutrition, can ameliorate aging and aging-associated diseases in invertebrate model organisms, rodents, primates, and humans. Recent findings indicate that meal timing is crucial, with both intermittent fasting and adjusted diurnal rhythm of feeding improving health and function, in the absence of changes in overall intake. Lowered intake of particular nutrients rather than of overall calories is also key, with protein and specific amino acids playing prominent r...
384 CitationsSource
#1Suzi Hong (UCSD: University of California, San Diego)H-Index: 25
#2William A. Banks (UW: University of Washington)H-Index: 93
Abstract Individuals living with HIV who are optimally treated with combination antiretroviral therapy (cART) can now lead an extended life. In spite of this remarkable survival benefit from viral suppression achieved by cART in peripheral blood, the rate of mild to moderate cognitive impairment remains high. A cognitive decline that includes impairments in attention, learning and executive function is accompanied by increased rates of mood disorders that together adversely impact the daily life...
112 CitationsSource
#1Alexander Karabatsiakis (University of Ulm)H-Index: 10
#2Iris-Tatjana Kolassa (University of Ulm)H-Index: 31
Last. Detlef E. Dietrich (MHH: Hannover Medical School)H-Index: 9
view all 5 authors...
Background Telomere shortening is a normal age-related process. However, premature shortening of telomeres in leukocytes – as has been reported in depression – may increase the risk for age-related diseases. While previous studies investigated telomere length in peripheral blood mononuclear cells (PBMCs) as a whole, this study investigated specific changes in the clonal composition of white blood cells of the adaptive immune system (CD4+ helper and CD8+ cytotoxic T lymphocytes, and CD20+ B lymph...
33 CitationsSource
#1Ana Paula ArrudaH-Index: 19
Last. Gökhan S. Hotamisligil (Harvard University)H-Index: 100
view all 6 authors...
Obesity-induced mitochondria stress and dysfunction results from disorganized mitochondria-associated ER membranes and excess calcium flux.
214 CitationsSource
#1Carola Rotermund (University of Tübingen)H-Index: 2
#2Felicia M. Truckenmüller (University of Tübingen)H-Index: 2
Last. Philipp J. Kahle (University of Tübingen)H-Index: 47
view all 4 authors...
Parkinson's disease (PD) and diabetes belong to the most common neurodegenerative and metabolic syndromes, respectively. Epidemiological links between these two frequent disorders are controversial. The neuropathological hallmarks of PD are protein aggregates composed of amyloid-like fibrillar and serine-129 phosphorylated (pS129) α-synuclein (AS). To study if diet-induced obesity could be an environmental risk factor for PD-related α-synucleinopathy, transgenic (TG) mice, expressing the human m...
23 CitationsSource
Cited By83
Summary Background & aim Oropharyngeal dysphagia (OD) can lead to a deficiency of antioxidant micronutrients. The aim of the present study was to investigate the relation between OD and nutritional status, antioxidant vitamins (β-carotene, vitamin E and C) and serum markers of the inflammatory response [C-reactive protein, myeloperoxidase (MPO), nitric oxide metabolites (NOx), tumor necrosis factor-α, interleukin (IL)-1β and IL-6] in adults and elderly. Methods A cross-sectional study was conduc...
#1Daniela F. Passos (UFSM: Universidade Federal de Santa Maria)H-Index: 3
#2João M. Bremm (UFSM: Universidade Federal de Santa Maria)H-Index: 1
Last. Maria Rosa Chitolina Schetinger (UFSM: Universidade Federal de Santa Maria)H-Index: 37
view all 11 authors...
The progression of the human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome can be efficiently interrupted by antiretroviral therapy. However, even successfully treated HIV-infected individuals are prone to develop non-AIDS-related diseases that affect the metabolism and several organs and systems. Biomarkers that predict the occurrence of comorbidities may help develop preventive measures. Current research shows that CD4(+) T cell counts and viral load do not predi...
#1Xavier Ayrignac (University of Montpellier)H-Index: 16
#2Clarisse Carra-Dalliere (University of Montpellier)H-Index: 8
Last. Pierre Labauge (University of Montpellier)H-Index: 33
view all 3 authors...
Abstract Inflammatory diseases of the central nervous system (CNS) mainly occur during early adulthood and multiple sclerosis (MS) represents the overwhelming majority of these disorders. Nevertheless, MS only rarely begins after 50 years and a diagnosis of late-onset MS should only be done when clinical as well as radiological and biological findings are typical of MS since the probability of misdiagnosis is higher in elderly patients. Indeed, in patients aged over 50 years, along with a relati...
#1Martin Škandík (SAV: Slovak Academy of Sciences)H-Index: 1
#2Nataša Mrvová (SAV: Slovak Academy of Sciences)H-Index: 3
Last. Lucia Račková (SAV: Slovak Academy of Sciences)H-Index: 15
view all 4 authors...
Abstract During brain ageing, microglia, the resident immune cells of the CNS, are immunologically activated and contribute to neuroinflammation, a vicious cycle that supports development of neurological disorders. Therapeutic approaches focus mainly on downregulation of their pro-inflammatory activated state that is associated with health benefits. Electrophilic compounds, such as natural quinones and their reduced pro-electrophilic precursors, flavonoids, represent a wide group of diverse subs...
2 CitationsSource
#1Vassiliki Tsiokou (RMIT: RMIT University)H-Index: 1
#2Thomas Kilindris (RMIT: RMIT University)H-Index: 1
Last. Eftihia K. Asprodini (RMIT: RMIT University)H-Index: 7
view all 6 authors...
Abstract Xenobiotic metabolism at menopause is an under-investigated topic, albeit women spend one-third of their life in the postmenopausal period. The present study examined the effect of menopause on the in vivo activities of CYP1A2, CYP2A6, xanthine oxidase (XO) and N-acetyltransferase-2 (NAT2) xenobiotic metabolizing enzymes. Enzyme activity was determined in 152 non-smoking volunteers following oral intake of a single dose of 200 mg caffeine and subsequent determination of caffeine metabol...
#1Thomas CrepinH-Index: 6
#2M. Legendre (French Institute of Health and Medical Research)H-Index: 2
Last. Jamal BamoulidH-Index: 12
view all 9 authors...
Resume L’immunosenescence participe au developpement des maladies liees a l’âge (infections, maladies cardiovasculaires et cancers). Les patients insuffisants renaux chroniques terminaux presentent une mortalite prematuree par rapport a la population generale, secondaire a une plus grande susceptibilite a la survenue d’infections, d’evenements cardiovasculaires et de cancers, pathologies habituellement rencontrees chez les personnes âgees et associees a l’immunosenescence. L’insuffisance renale ...
1 CitationsSource
#1De Cicco (University of Tübingen)
#1Silvia De Cicco (German Center for Neurodegenerative Diseases)
Last. Meike JakobiH-Index: 1
view all 14 authors...
Increasing evidence suggests a role for interferons (IFNs) in neurodegeneration. Parkinson9s disease (PD) associated kinase LRRK2 has been implicated in IFN type II (IFN) response in infections and nigral neuronal loss. However, whether and how LRRK2 synergizes with IFN-γ still remains unclear. Here, we employed dopaminergic (DA) neurons and microglia differentiated from patient induced pluripotent stem cells to unravel the role of IFN-γ in LRRK2-PD. We show that IFN-γ induces LRRK2 expression i...
#1Maria Aliseychik (MSU: Moscow State University)H-Index: 1
#2Anton Patrikeev (RAS: Russian Academy of Sciences)
Last. Evgeny I. Rogaev (MSU: Moscow State University)H-Index: 39
view all 7 authors...
The immune system contributes to neurodegenerative pathologies. However, the roles of γδ T cells in Alzheimer’s disease (AD) are poorly understood. Here, we evaluated somatic variability of T-cell receptor γ genes (TRGs) in patients with AD. We performed deep sequencing of the CDR3 region of TRGs in patients with AD and control patients without dementia. TRG clones were clearly detectable in peripheral blood (PB) and non-neuronal cell populations in human brains. TRG repertoire diversity was red...
#1Davide De Biase (University of Naples Federico II)H-Index: 6
#2G. Piegari (University of Naples Federico II)H-Index: 9
Last. Orlando Paciello (University of Naples Federico II)H-Index: 22
view all 10 authors...
NLRP3 inflammasome is a multiprotein complex that can sense several stimuli such as autophagy dysregulation and increased reactive oxygen species production stimulating inflammation by priming the maturation of proinflammatory cytokines interleukin-1beta and interleukin-18 in their active form. In the aging brain, these cytokines can mediate the innate immunity response priming microglial activation. Here, we describe the results of immunohistochemical and molecular analysis carried out on bovin...
1 CitationsSource
Cognitive dysfunction, one of the major concerns of increased life expectancy, is prevalent in patients with metabolic disorders. Added to the inflammation in the context of aging (inflammaging), low-grade chronic inflammation (metaflammation) accompanies metabolic diseases. Peripheral and central inflammation underlie metabolic syndrome - related cognitive dysfunction. The gut microbiota is increasingly recognized to be linked to both inflammaging and metaflammation in parallel to the pathophys...
2 CitationsSource