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Alzheimer's disease (AD) is one of the brain's neurodegenerative diseases. It is distinguished by a progressive mental, social, and behavioral deterioration. It affects the person's capacity, thinking, attention, reasoning, social behavior and functionality to achieve independence. The classical diagnosis process of AD consists of variety of neuroimaging scan approaches such as computerized tomography, magnetic resonance imaging and positron emission tomography. Classical cerebrospinal fluid...

Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are characterized by the misfolding and aggregation of alpha-synuclein (αSyn). Compelling evidence showed that αSyn aggregates exist as distinct conformational strains in different synucleinopathies. Recently, we reported that the αSyn Seed Amplification Assay (αSyn-SAA) can amplify and distinguish αSyn strains from PD and MSA. In this study, we investigate whether MSA-seeded, SAA-amplified αSyn fibrils...

While the clinical utility of conventional antibody therapies is undeniable, their therapeutic potential is often constrained high antigen loads and the recycling of antibody-antigen complexes via neonatal Fc receptor (FcRn). Here, we present a platform, based on a design similar to bispecific antibodies, FcγRIIb-Targeting Chimeras (FcRTAC). These constructs recognise antigens with one arm and bind FcγRIIb with the other arm to harness the unique endocytic properties of FcγRIIb to direct the...

Biological ageing is a systemic, multifactorial process driven by progressive molecular and cellular alterations whose complexity necessitates systems-level approaches. Advances in high-throughput omics technologies now allow simultaneous quantification of millions of biomolecules from a single specimen, enabling longitudinal, integrative profiling across multiple molecular layers. This review synthesizes recent progress in applying genomics, epigenomics, metabolomics and microbiomics to ageing...

Organ shortage remains a major barrier in treating end-stage organ failure, with many patients dying while waiting or becoming medically unfit by the time an organ is offered. A substantial number of organs, particularly from older donors, remain unused due to concerns over age-related decline in quality. This review highlights emerging strategies to rejuvenate and optimize such organs by mitigating ischemia-reperfusion injury and reducing age-related immunogenicity. Advances in organ...

The human utricle is a vestibular organ essential for balance, a function that declines with age. With the aging population projected to double to 2 billion by 2050 and no pharmaceutical or biological treatments available, balance disorders represent a significant unmet medical need. The utricle is composed of sensory and non-sensory cells, which are closely related. Non-sensory cells have limited capacity to regenerate sensory cells and, therefore, are a relevant therapeutic target. In this...

Aging is accompanied by profound alterations in the immune system; yet, an accurate prediction of immunological age remains challenging. While transcriptomic approaches have yielded insights into immune aging, protein-level profiling and machine learning-based prediction tools remain underdeveloped. Here, we employ mass cytometry to analyse murine splenic CD45⁺ immune cells across various age groups, profiling the expression of 30 protein markers and monitoring age-related immune changes. By...

Iron-sulfur (Fe-S) clusters are essential metallocofactors that perform a multitude of biological functions^(1-7). Their synthesis is tightly regulated and defects in this process lead to severe diseases^(8-10), such as Friedreich's ataxia, which is caused by defective expression of frataxin (FXN)^(11). However, the underlying mechanisms that regulate this process remain unclear. Here we show that efficient Fe-S cluster assembly requires a fine-tuned balance in the ratio of FXN and ferredoxin-2...

Reproduction is hypothesized to constrain lifespan^(1,2) and contribute to sex differences in ageing^(3-5). Various sterilization and contraception methods inhibit reproduction, but predictions differ for how these influence survival, depending on sex⁵, how sex hormones are affected⁴ and species life history⁶. Here, using data from mammalian species housed in zoos and aquariums worldwide, we show that ongoing hormonal contraception and permanent surgical sterilization are associated with...

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The progressive aging of the Italian population and the increasing prevalence of multimorbidity and frailty call for a reorganization of health and social care services. In this paper we aim to critically examine Ministerial Decree 77/2022, within Mission 6 of the National Recovery and Resilience Plan, which establishes new models and standards for community-based care and offers an unique opportunity to deliver care that is closer to people's homes, fostering a holistic approach that combines...

Caloric restriction (CR) extends the health and lifespan of diverse species. When fed once daily, CR-treated mice rapidly consume their food and endure a prolonged fast between meals. As fasting is associated with a rise in circulating ketone bodies, we investigated the role of ketogenesis in CR using mice with whole-body ablation of Hmgcs2, the rate-limiting enzyme producing the main ketone body β-hydroxybutyrate (βHB). Here, we report that Hmgcs2 is largely dispensable for many metabolic...

CONCLUSION: In this prospective cohort study, osteosarcopenia increased the risk of frailty. Our interaction analysis suggests therapies targeting bone density and grip strength may mitigate frailty.

The rapid advancement of spatially resolved transcriptomics (SRT) technology enables gene expression profiling across tissue locations while preserving spatial context. Gene co-expression analysis in SRT data provides critical insights into how genes function together within the tissue microenvironment. However, existing methods fail to effectively capture the joint influence of gene-gene interactions and spatial dependencies, limiting their biological interpretability. Here, we introduce spMOCA...

Aging in females is characterized by dysfunctional ovaries (DOs). While human umbilical cord mesenchymal stem cell (HucMSC)-derived extracellular vesicles (EVs) have shown promise in ameliorating DO, the mechanisms underlying their effects remain poorly understood. In this study, we investigated the therapeutic potential of growth differentiation factor 9 (GDF-9)-overexpressing EVs (GOEs) on granulosa cells. We identified the activin A receptor type 1B (ACVR1B) as a critical target for the...

Atherosclerosis, a key pathological basis of cardio-cerebrovascular diseases, is closely associated with aging and endothelial cell senescence. The role of microRNAs (miRNAs) in regulating endothelial cell senescence and atherosclerosis remains incompletely understood. In this study, we discovered that miR-375-3p expression was significantly elevated in the serum of both aged and atherosclerotic mice. Overexpression of miR-375-3p induced endothelial cell senescence, evidenced by increased...

INTRODUCTION: The aging global population underscores the need to understand brain aging and its links to neurodegenerative diseases. While most brain aging studies use cognitive impairment as exclusion criteria, preclinical biomarkers may influence results, potentially masking early pathological effects. This study evaluates how preclinical AD and vascular biomarkers impact brain aging models in cognitively normal subjects.