Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 1869 - 1869

Опубликована: Янв. 18, 2023

Aging is the most prominent risk factor for late-onset Alzheimer’s disease. associates with a chronic inflammatory state both in periphery and central nervous system, evidence thereof mechanisms leading to neuroinflammation being discussed. Nonetheless, significantly enhanced by accumulation of amyloid beta accelerates progression disease through various pathways discussed present review. Decades clinical trials targeting 2 abnormal proteins disease, tau, led many failures. As such, via different strategies could prove valuable therapeutic strategy, although much research still needed identify appropriate time window. Active focusing on identifying early biomarkers help translating these novel from bench bedside.

Язык: Английский

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Association between frailty and depression: A bidirectional Mendelian randomization study

Science Advances, Год журнала: 2023, Номер 9(38)

Опубликована: Сен. 20, 2023

Frailty and depression were linked in observational studies, but the causality remains ambiguous. We intended to explore it using Mendelian randomization (MR). obtained frailty genome-wide association study (GWAS) data from UK Biobank TwinGen meta-analysis, GWAS Psychiatric Genomics Consortium (PGC) FinnGen (respectively recorded as PD FD). performed univariable multivariable-adjusted MR with adjustments for body mass index (BMI) physical activity (PA). was significantly associated elevated risks of (OR, 1.860; 95% CI, 1.439 2.405; P < 0.001) FD 1.745; 1.193 2.552; = 0.004), meanwhile a susceptible factor (PD: β, 0.146; 0.086 0.201; 0.001; FD: 0.112; 0.051 0.174; 0.001). This robust after BMI or PA. Our provides evidence bidirectional causal between genetic perspectives.

Язык: Английский

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Fiber-Type Shifting in Sarcopenia of Old Age: Proteomic Profiling of the Contractile Apparatus of Skeletal Muscles

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2415 - 2415

Опубликована: Янв. 26, 2023

The progressive loss of skeletal muscle mass and concomitant reduction in contractile strength plays a central role frailty syndrome. Age-related neuronal impairments are closely associated with sarcopenia the elderly, which is characterized by severe muscular atrophy that can considerably lessen overall quality life at old age. Mass-spectrometry-based proteomic surveys senescent human muscles, as well animal models sarcopenia, have decisively improved our understanding molecular cellular consequences fiber-type shifting during aging. This review outlines spectrometric identification proteome-wide changes atrophying focus on proteins potential markers distribution patterns. observed trend fast-to-slow transitions individual muscles aging process most likely linked to preferential susceptibility fast-twitching fibers atrophy. Studies models, including mostly aged rodent confirmed shifting. analysis fast versus slow isoforms key proteins, such myosin heavy chains, light actins, troponins tropomyosins, suggests them suitable bioanalytical tools

Язык: Английский

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Diet for the prevention and management of sarcopenia

Metabolism, Год журнала: 2023, Номер 146, С. 155637 - 155637

Опубликована: Июнь 21, 2023

Sarcopenia is a geriatric condition characterized by progressive loss of skeletal muscle mass and strength, with an increased risk adverse health outcomes (e.g., falls, disability, institutionalization, reduced quality life, mortality). Pharmacological remedies are currently unavailable for preventing the development sarcopenia, halting its progression, or impeding negative outcomes. The most effective strategies to contrast sarcopenia rely on adoption healthier lifestyle behaviors, including adherence high-quality diets regular physical activity. In this review, role nutrition in prevention management summarized. Special attention given current "blockbuster" dietary regimes agents used counteract age-related wasting, together their putative mechanisms action. Issues related design implementation nutritional discussed, focus unanswered questions appropriate timing interventions preserve function into old age. A brief description also provided new technologies that can facilitate personalized plans sarcopenia.

Язык: Английский

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Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective

Ageing Research Reviews, Год журнала: 2023, Номер 91, С. 102044 - 102044

Опубликована: Авг. 28, 2023

According to the Geroscience concept that organismal aging and age-associated diseases share same basic molecular mechanisms, identification of biomarkers age can efficiently classify people as biologically older (or younger) than their chronological (i.e. calendar) is becoming paramount importance. These will be in fact at higher lower) risk for many different diseases, including cardiovascular neurodegeneration, cancer, etc. In turn, patients suffering from these are healthy age-matched individuals. Many correlate with have been described so far. The aim present review discuss usefulness some (especially soluble, circulating ones) order identify frail patients, possibly before appearance clinical symptoms, well diseases. An overview selected discussed this regard, particular we focus on related metabolic stress response, inflammation, cell death (in neurodegeneration), all phenomena connected inflammaging (chronic, low-grade, inflammation). second part review, next-generation markers such extracellular vesicles cargos, epigenetic gut microbiota composition, discussed. Since recent progresses omics techniques allowed an exponential increase production laboratory data also field age, making it difficult extract biological meaning huge mass available data, Artificial Intelligence (AI) approaches increasingly important strategy extracting knowledge raw providing practitioners actionable information treat patients.

Язык: Английский

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Mitochondrial Quantity and Quality in Age-Related Sarcopenia

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2052 - 2052

Опубликована: Фев. 8, 2024

Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with complex pathophysiology. Among factors underlying development of sarcopenia are progressive demise motor neurons, transition from fast to slow myosin isoform (type II type I fiber switch), decrease satellite cell number function. Mitochondrial dysfunction has been indicated as key contributor myocyte loss physical performance aging. Several systems have implicated regulation plasticity trophism such fine-tuned between stimulator protein synthesis, mechanistic target rapamycin (mTOR), inhibitor mTOR, AMP-activated kinase (AMPK), that promotes catabolism. Here, we provide an overview molecular mechanisms linking mitochondrial signaling quality homeostasis discuss main pathways elicited by their imbalance during age-related wasting. We also lifestyle interventions (i.e., exercise nutrition) may be exploited preserve function aged muscle. Finally, illustrate emerging possibility rescuing tissue through transplantation.

Язык: Английский

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Aging-related hyperphosphatemia triggers the release of TNF-α from macrophages, promoting indicators of sarcopenia through the reduction of IL-15 expression in skeletal muscle

Life Sciences, Год журнала: 2025, Номер 368, С. 123507 - 123507

Опубликована: Фев. 25, 2025

Язык: Английский

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Inflammaging and Brain Aging

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10535 - 10535

Опубликована: Сен. 30, 2024

Progress made by the medical community in increasing lifespans comes with costs of incidence and prevalence age-related diseases, neurodegenerative ones included. Aging is associated a series morphological changes at tissue cellular levels brain, as well impairments signaling pathways gene transcription, which lead to synaptic dysfunction cognitive decline. Although we are not able pinpoint exact differences between healthy aging neurodegeneration, research increasingly highlights involvement neuroinflammation chronic systemic inflammation (inflammaging) development age-associated via pathogenic cascades, triggered dysfunctions circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender susceptibility course neurodegeneration that appear be mediated glial cells emphasize need for future this area an individualized therapeutic approach. rejuvenation still its very early infancy, accumulated knowledge on various involved promoting senescence opens perspective interfering these preventing delaying senescence.

Язык: Английский

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Pan-cancer secreted proteome and skeletal muscle regulation: insight from a proteogenomic data-driven knowledge base

Functional & Integrative Genomics, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 15, 2025

Язык: Английский

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Mitochondria-Derived Vesicles and Inflammatory Profiles of Adults with Long COVID Supplemented with Red Beetroot Juice: Secondary Analysis of a Randomized Controlled Trial

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1224 - 1224

Опубликована: Янв. 30, 2025

In a recent clinical trial, beetroot juice supplementation for 14 days yielded positive effects on systemic inflammation in adults with long COVID. Here, we explored the relationship between circulating markers of mitochondrial quality and COVID as well impact administration those markers. We conducted secondary analyses placebo-controlled randomized trial testing remedy against Analyses were 25 participants, 10 assigned to placebo (mean age: 40.2 ± 11.5 years, 60% women) 15 allocated 38.3 7.7 53.3% women). Extracellular vesicles purified from serum by ultracentrifugation assayed components electron transport chain DNA (mtDNA) Western blot droplet digital polymerase reaction (ddPCR), respectively. Inflammatory cell-free mtDNA quantified through multiplex immunoassay ddPCR, Beetroot decreased levels interleukin (IL)-1β, IL-8, tumor necrosis factor alpha, no control. Significant negative associations observed vesicular control performance 6 min walk test flow-mediated dilation irrespective group allocation. These findings suggest that an amelioration quality, possibly mediated mitochondria-derived vesicle recycling, may be among mechanisms supporting improvements physical endothelial function during resolution

Язык: Английский

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