Counteracting Immunosenescence—Which Therapeutic Strategies Are Promising? DOI Creative Commons

Christoph Hieber,

Stephan Grabbe, Matthias Bros

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(7), P. 1085 - 1085

Published: July 6, 2023

Aging attenuates the overall responsiveness of immune system to eradicate pathogens. The increased production pro-inflammatory cytokines by innate cells under basal conditions, termed inflammaging, contributes impaired towards pathogen-mediated stimulation and limits antigen-presenting activity. Adaptive responses are attenuated as well due lowered numbers naïve lymphocytes their antigen-specific stimulation. Additionally, immunoregulatory cell types, comprising regulatory T myeloid-derived suppressor cells, that inhibit activity adaptive elevated. This review aims summarize our knowledge on cellular molecular causes immunosenescence while also taking into account senescence effects constitute evasion mechanisms in case chronic viral infections cancer. For tumor therapy numerous nanoformulated drugs have been developed overcome poor solubility compounds enable cell-directed delivery order restore functions, e.g., addressing dysregulated signaling pathways. Further, nanovaccines which efficiently address mount sustained anti-tumor clinically evaluated. senolytics selectively deplete senescent being tested a number clinical trials. Here we discuss potential use such improve anti-aging therapy.

Language: Английский

Mechanisms of spermidine-induced autophagy and geroprotection DOI Open Access
Sebastian J. Hofer, Anna Katharina Simon, Martina Bergmann

et al.

Nature Aging, Journal Year: 2022, Volume and Issue: 2(12), P. 1112 - 1129

Published: Dec. 22, 2022

Language: Английский

Citations

100
Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer DOI Creative Commons
Guoshu Bi, Jiaqi Liang, Yunyi Bian

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 19, 2024

Abstract Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload lipid peroxides, in cancer therapy is impeded our limited understanding intersection tumour’s metabolic feature and ferroptosis vulnerability. In present study, arginine identified as a ferroptotic promoter using metabolites library. This effect mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property H 2 O -dependent manner. Notably, expression ornithine decarboxylase 1 (ODC1), critical enzyme catalysing polyamine synthesis, significantly activated signal——iron overload——through WNT/MYC signalling, well subsequent elevated thus forming ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H positive feedback loop that amplifies ferroptosis. Meanwhile, we notice cells release enhanced polyamine-containing extracellular vesicles into microenvironment, thereby further sensitizing neighbouring accelerating “spread” tumour region. Besides, supplementation also sensitizes or xenograft tumours radiotherapy chemotherapy inducing Considering are often characterized intracellular pools, results indicate metabolism exposes targetable vulnerability represents exciting opportunity for therapeutic strategies cancer.

Language: Английский

Citations

37
The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing DOI Creative Commons
Yuqing Liu, Yejun Tan, Zheyu Zhang

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 23, 2024

Abstract Ageing is a crucial risk factor for Alzheimer’s disease (AD) and characterised by systemic changes in both intracellular extracellular microenvironments that affect the entire body instead of single organ. Understanding specific mechanisms underlying role ageing development can facilitate treatment ageing-related diseases, such as AD. Signs brain have been observed AD patients animal models. Alleviating pathological caused dramatically ameliorate amyloid beta- tau-induced neuropathological memory impairments, indicating plays pathophysiological process In this review, we summarize impact several age-related factors on propose preventing promising strategy improving cognitive health.

Language: Английский

Citations

33
Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer’s Disease Therapeutics DOI Creative Commons
Daniela Dias, Renato Socodato

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 279 - 279

Published: Jan. 23, 2025

Alzheimer’s disease (AD) is traditionally viewed through the lens of amyloid cascade hypothesis, implicating amyloid-beta and tau protein aggregates as main pathological culprits. However, burgeoning research points to brain’s resident immune cells, microglia, critical players in AD pathogenesis, progression, potential therapeutic interventions. This review examines dynamic roles microglia within intricate framework AD. We detail involvement these cells neuroinflammation, explaining how their activation response fluctuations may influence trajectory. further elucidate complex relationship between pathology. study highlights dual nature which contribute both aggregation clearance protein. Moreover, an in-depth analysis interplay unveils significant, yet often overlooked, impact this interaction on neurodegeneration Shifting from conventional approaches, we assess current treatments primarily targeting introduce novel strategies that involve manipulating microglial functions. These innovative methods herald a paradigm shift management Finally, explore field precision diagnosis pursuit robust biomarkers. underline more profound comprehension biology could enrich essential areas, potentially paving way for accurate diagnostic tools tailored treatment strategies. In conclusion, expands perspective pathology treatment, drawing attention multifaceted microglia. As continue enhance our understanding microglial-focused interventions emerge promising frontier bolster arsenal fight against

Language: Английский

Citations

4
Targeting autophagy in Alzheimer’s disease: Animal models and mechanisms DOI Creative Commons
Xiaowen Zhang, Xiangxing Zhu, Dongsheng Tang

et al.

动物学研究, Journal Year: 2023, Volume and Issue: 44(6), P. 1132 - 1145

Published: Jan. 1, 2023

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that leads to cognitive impairment and memory loss. Emerging evidence suggests autophagy plays important role in the pathogenesis of AD through regulation amyloid-beta (Aβ) tau metabolism, dysfunction exacerbates amyloidosis pathology. Therefore, targeting may be effective approach for treatment AD. Animal models are considered useful tools investigating pathogenic mechanisms therapeutic strategies diseases. This review aims summarize pathological alterations representative animal present recent studies on newly discovered autophagy-stimulating interventions models. Finally, opportunities, difficulties, future directions therapy discussed.

Language: Английский

Citations

23
Focusing on mitochondria in the brain: from biology to therapeutics DOI Creative Commons

Nanshan Song,

Shuyuan Mei,

Xiang-Xu Wang

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: April 17, 2024

Abstract Mitochondria have multiple functions such as supplying energy, regulating the redox status, and producing proteins encoded by an independent genome. They are closely related to physiology pathology of many organs tissues, among which brain is particularly prominent. The demands 20% resting metabolic rate holds highly active mitochondrial activities. Considerable research shows that mitochondria function, while defects induce or exacerbate in brain. In this review, we provide comprehensive advances biology involved functions, well mitochondria-dependent cellular events pathology. Furthermore, various perspectives explored better identify roles neurological diseases neurophenotypes diseases. Finally, therapies discussed. Mitochondrial-targeting therapeutics showing great potentials treatment

Language: Английский

Citations

15
Unveiling the impact of aging on BBB and Alzheimer's disease: Factors and therapeutic implications DOI
Niraj Kumar Jha, Niraj Kumar Jha, Mohana Vamsi Nuli

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102224 - 102224

Published: Feb. 10, 2024

Language: Английский

Citations

14
Synergistic effect of spermidine and ciprofloxacin against Alzheimer's disease in male rat via ferroptosis modulation DOI

Menna Allah M. Youssef,

Tarek M. Mohamed,

Azza Bakry

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 263, P. 130387 - 130387

Published: Feb. 23, 2024

Language: Английский

Citations

10
Investigating the metabolite signature of an altered oral microbiota as a discriminant factor for multiple sclerosis: a pilot study DOI Creative Commons
Léo Boussamet, Emmanuel Montassier, Camille Mathé

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 2, 2024

Abstract In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, role other microbiomes in body MS has not been fully elucidated. a pilot case-controlled study, we carried out simultaneous characterization faecal and oral conducted an in-depth analysis bacterial associated with MS. Using 16S rRNA sequencing metabolic inference tools, compared oral/faecal metabolism pathways French patients (n = 14) healthy volunteers (HV, n 21). A classification model based on metabolite flux balance was established validated independent German cohort (MS 12, HV 38). Our revealed decreases diversity indices compartmentalization, depletion commensal bacteria ( Aggregatibacter Streptococcus saliva Coprobacter Roseburia faeces) enrichment inflammation-associated Leptotrichia Fusobacterium Enterobacteriaceae Actinomyces faeces). Several microbial were also altered (the polyamine pathway remodelling surface antigens energetic metabolism) while production (nitrogen nucleoside). Based this analysis, identified specific signature patients, that could discriminate from rheumatoid arthritis patients. This allowed us create validate discrimination cohort, which reached specificity 92%. Overall, study highlights need health implications autoimmune diseases larger scale suggests knowledge salivary microbiome help guide identification new pathogenic mechanisms

Language: Английский

Citations

10
Neuroinflammaging and the Immune Landscape: The Role of Autophagy and Senescence in Aging Brain DOI Creative Commons

Rajesh Tamatta,

Varsha Pai,

Charu Jaiswal

et al.

Biogerontology, Journal Year: 2025, Volume and Issue: 26(2)

Published: Feb. 5, 2025

Abstract Neuroinflammation is closely linked to aging, which damages the structure and function of brain. It caused by intricate interactions immune cells in aged brain, such as dysregulated glial dysfunctional astrocytes. Aging-associated chronic low inflammation, referred neuroinflammaging, shows an upregulated proinflammatory response. Autophagy senescence play crucial roles moderators aging neuroinflammatory responses. The neuroimmune system, dystrophic cells, release factors alter blood-brain barrier, causing a landscape. Chronic inflammation combined with deteriorating neurons exacerbate neurological disorders decline cognitive function. This review highlights neuroinflammaging mechanism associated interplay central nervous system cellular senescence, autophagy regulation brain's under conditions. Moreover, microglia peripheral process brain have also been discussed. Determining treatment targets comprehending mechanisms that influence necessary decrease neuroinflammation.

Language: Английский

Citations

1