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Aging in the healthy brain is characterized by a low-grade, chronic, and sterile inflammatory process known as neuroinflammaging. This condition, mainly consisting in an up-regulation of the inflammatory response at the brain level, contributes to the pathogenesis of age-related neurodegenerative disorders. Development of this proinflammatory state involves the interaction between genetic and environmental factors, able to induce age-related epigenetic modifications. Indeed, the exposure to environmental compounds, drugs, and infections, can contribute to epigenetic modifications of DNA methylome, histone fold proteins, and nucleosome positioning, leading to epigenetic modulation of neuroinflammatory responses. Furthermore, some epigenetic modifiers, which combine and interact during the life course, can contribute to modeling of epigenome dynamics to sustain, or dampen the neuroinflammatory phenotype. The aim of this review is to summarize current knowledge about neuroinflammaging with a particular focus on epigenetic mechanisms underlying the onset and progression of neuroinflammatory cascades in the central nervous system; furthermore, we describe some diagnostic biomarkers that may contribute to increase diagnostic accuracy and help tailor therapeutic strategies in patients with neurodegenerative diseases.
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http://dx.doi.org/10.14336/AD.2023.1001 | DOI Listing |
Eur J Intern Med
September 2025
Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; Istituti Clinici Scientifici ICS Maugeri - S.p.A.-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Scientifico di Telese Terme, Telese, Italy. Electronic address:
The fraction that the elderly represent in the world's population is growing rapidly; numerous alterations that impact all organs and systems, including the immune system, are related to aging. A complex process common in the elderly, known as immunosenescence, is characterized by a decreased ability to respond to vaccination as well as an increased risk of bacterial and viral infections, autoimmune, cardiovascular and neurodegenerative diseases. These processes are associated with alterations in the innate and adaptive immune system and lead to a condition of chronic low-grade inflammation, referred to as inflammaging.
View Article and Find Full Text PDFNat Aging
September 2025
IFOM-ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Aging is the main risk factor for Parkinson's disease (PD), yet our understanding of how age-related mechanisms contribute to PD pathophysiology remains limited. We conducted a longitudinal analysis of blood samples from the Parkinson's Progression Markers Initiative cohort to investigate DNA damage in PD. Patients with PD exhibited disrupted DNA repair pathways and biased suppression of longer transcripts, indicating age-related, transcription-stalling DNA damage.
View Article and Find Full Text PDFLearn Mem
September 2025
Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana 47405, USA
While cognitive function remains stable for majority of the lifespan, many functions sharply decline in later life. Women have higher rates of neurodegenerative diseases that involve memory loss, including Alzheimer's disease. This sex disparity may be due to longer life expectancies when compared to men; women outlive men by roughly 5 years globally.
View Article and Find Full Text PDFClin Nucl Med
September 2025
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.
Background: Alzheimer disease (AD) is characterized by amyloid-β plaques (A), tau tangles (T), and neurodegeneration (N), collectively defining the ATN framework. While imaging biomarkers are well-established, the prognostic value of plasma biomarkers in predicting cognitive decline remains underexplored. This study compares plasma and imaging A/T/N biomarkers in predicting cognitive decline and evaluate the impact of combining biomarkers across modalities.
View Article and Find Full Text PDFAging Cell
September 2025
CREEC/CANECEV, MIVEGEC (CREES) Department, University of Montpellier, CNRS, IRD, Montpellier, France.
Aging, and by extension age-related diseases, has traditionally been understood through classical evolutionary genetic models, such as the mutation accumulation and antagonistic pleiotropy theories. However, these frameworks primarily focus on the declining efficacy of organismal-level selection against mutations with deleterious effects in late life. Here, we propose a novel hypothesis: many chronic diseases associated with aging may emerge, at least in part, as a result of selection acting at lower organizational levels, including non-replicative biological entities, enabled by the relaxation of selective pressures that constrained within-organism evolutionary processes in early life.
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