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Our perspective addresses one of the most pressing and timely debates in contemporary neurology and health policy: whether the recent approval of anti-amyloid monoclonal antibodies for Alzheimer's disease should extend to all individuals with mild cognitive impairment (MCI; a large population of tens of millions of individuals worldwide mainly represented in Countries with aged population) who test positive for amyloid biomarkers, despite wide variability in prognosis and therapeutic response...

Dysregulated mitochondrial DNA (mtDNA) promotes inflammatory response and disease progression. However, the mechanism and role of mtDNA-mediated inflammatory activation in the pathogenesis of Parkinson's disease (PD) are not yet clear. This study demonstrates that the injection of mtDNA into the substantia nigra pars compacta induces PD pathology in mice, characterized by the loss of dopaminergic (DA) neurons and the activation of microglia. Transcriptomic profiling of magnetic-activated cell...

Brain derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) play crucial roles in neuronal development, synaptic transmission, and neuroplasticity. Deficits in BDNF/TrkB signalling and trafficking have been identified in several neurodegenerative diseases, including Alzheimer's disease (AD). Individuals with Down syndrome (DS) are at an increased risk of developing AD compared to the general population. Basal forebrain neurons (BFNs) are among the first to...

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The global burden of Parkinson disease (PD) is rapidly shifting towards low-income and middle-income countries (LMICs), which already account for 44% of all individuals with PD. Despite this trend, the populations of LMICs and other under-represented populations defined by ethnicity, sex, geography and minority groups within high-income countries remain largely excluded from PD research. The continuation of these disparities limits our knowledge of disease biology and restricts the applicability...

Detecting senescent cells from single-cell RNA-seq data remains challenging due to the weak and non-specific expression of canonical markers. Here, we demonstrate that simple expansion of these low-signal marker sets does not improve detection accuracy. To address this limitation, we develop ICE (Imputation-based Cell Enrichment), a computational framework that integrates expression imputation with marker refinement. ICE improves the detection of senescent cells in pancreatic β cells and...

This systematic review with meta-analysis aimed to analyze the effects of exergaming (EXG) versus conventional therapies on muscle strength, balance, and fear of falling in healthy older people. A systematic literature search was conducted in six generic databases (PubMed, Medline, CINAHL Complete, Scopus, Cochrane Library, and Web of Science) with no start date restrictions until May 2025. The PRISMA, TESTEX, Rob 2 and GRADE tools were used to assess the methodological quality and certainty of...

Alzheimer's disease (AD) presents a critical global challenge, accounting for over 60 % of the 57 million current dementia cases worldwide, with prevalence projected to exceed 100 million by 2050. Traditional diagnostic approaches, such as cerebrospinal fluid (CSF) analysis and neuroimaging are constrained by invasiveness, high costs, and limited accessibility, particularly problematic in aging population where early detection is crucial for effective intervention. This review synthesizes recent...

Bioorthogonal chemistry has become a robust toolbox with growing applications in biology and medicine. To meet diverse needs in research, new types of on-demand bioorthogonal reactions capable of responding to biological triggers or exogenous stimuli are highly valuable, to achieve spatial and temporal control over reactions in living systems. Elevated levels of reactive oxygen species have been implicated in aging and multiple diseases, serving as remarkable endogenous triggers for prodrugs,...

Laminopathies are a group of rare disease due to mutations in the LMNA gene, which is crucial for nuclear integrity and cellular rigidity. Depending on the mutation, the disease manifests in striated muscles, adipose tissues, nerves, and the heart. Although many laminopathic patients exhibit accelerated aging syndromes, the connection as to why loss of LMNA drives aging remains unknown. Herein, we present evidence that cardiomyocytes from laminopathic heart sections exhibit shortened telomeres....

Pyroptosis plays a crucial role in immune defense against infections and endogenous threats by eliminating harmful cells and modulating the immune response through inflammation. However, the natural activation of pyroptosis involves intricate signaling pathways, posing significant challenges for its artificial manipulation in research and therapies. Here, we present DAMAGE (Death Manipulation Gene), an innovative system that integrates gasdermins within the type III-E CRISPR framework, enabling...

Frailty, characterized by diminished physiological reserve and increased vulnerability to stressors, is a common geriatric syndrome associated with adverse health outcomes. While recent seminal studies have reported conflicting findings regarding taurine, a sulfur-containing amino acid with antioxidant properties, and its relationship with aging, these discrepancies may reflect the heterogeneity of aging trajectories among older adults that chronological age alone fails to capture. Here, we...

People with HIV (PWH) on combination antiretroviral therapy have an elevated risk for aging-related non-AIDS comorbidities. We assess whether HIV infection accelerates biological aging in two independent cohorts of PWH using six organ-specific and three organism-wide aging clocks derived from plasma proteomics of healthy individuals. Proteomic age acceleration significantly correlates with DNA methylation age and is linked to comorbidities and mortality. HIV infection accelerates systemic...

The decline in estrogen following menopause is a major driver of metabolic and immune dysfunction in aging females. While hormone replacement therapy improves many of these outcomes, its clinical use remains limited due to concerns regarding estrogen-sensitive malignancies. Tissue-selective estrogen complexes (TSECs), which combine estrogens with selective estrogen receptor modulators (SERMs) such as tamoxifen (TAM), represent a promising strategy to preserve the metabolic and immunological...

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Detecting senescent cells from single-cell RNA-seq data remains challenging due to the weak and non-specific expression of canonical markers. Here, we demonstrate that simple expansion of these low-signal marker sets does not improve detection accuracy. To address this limitation, we develop ICE (Imputation-based Cell Enrichment), a computational framework that integrates expression imputation with marker refinement. ICE improves the detection of senescent cells in pancreatic β cells and...

CONCLUSION: Among older Indian adults, elevated NfL and GFAP levels were strongly associated with poor cognitive performance. These biomarkers could aid future dementia screening and prognostication efforts. Longitudinal studies are needed to validate their role in large-scale screening programs.

Exercise improves cognition, mental wellbeing, and protects against neurodegeneration. However, most prior neuroscience studies have focused on localized brain changes without quantifying their impact on brain ageing. To quantify the effect of resistance training on brain health using longitudinal assessments. Using resting-state functional magnetic resonance imaging (rs-fMRI) data from 2,433 healthy adults, we trained models to predict brain age and applied them to 309 participants from the...

CONCLUSIONS: We provide our systematic testing framework as an open-source, publicly available tool that can be utilised to offer novel insights into the genes, tissues and cell types involved in any disease, with the potential for informing drug development and delivery strategies.

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