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Alzheimer's disease and related dementia (ADRD) represents a growing public health burden, especially in low- and middle-income countries. Yet, most studies focus on Non-Hispanic white (NHW) populations from high-income countries. This study investigates plasma proteomic signatures associated with amyloid pathology in African populations. Nigerian older adults from the VALIANT study and participants from a Tanzanian study, with available biomarker quantification in plasma are employed. For...

No abstract

Detection of Alzheimer's disease (AD) before the development of clinical symptoms is critical for enabling the use of new treatments. Circular RNAs (circRNAs) are highly stable non-coding RNAs enriched in the brain that can cross the blood-brain barrier. Here, analyzing blood data from 1,221 individuals with AD and healthy individuals, we identified 34 circRNAs associated with AD status. A predictive model including these 34 circRNAs was comparable to plasma phosphorylated Tau-217 (pTau217) in...

Age-related breakdown of the blood-brain barrier (BBB) is associated with cerebrovascular and neurodegenerative diseases, yet its underlying mechanisms remain unclear. Here, we find that BBB leakage begins in midlife and is driven primarily by increased endothelial caveolar transcytosis rather than tight junction disruption. AAV-mediated knockdown of caveolin-1 or restoration of Mfsd2a expression reduces endothelial vesicle formation and BBB leakage in aged mice. Transforming growth factor...

Conventional BMI-based classifications, even when combined with traditional cardiometabolic risk factors, limit precision in aging-related risk assessment. Here, we perform metabolomic analysis in 13,202 older adults from the natural aging cohort (NCT04517513). Leveraging a panel of 39 core metabolites, we develop accurate and interpretable machine learning models to identify metabolic dysfunction across different BMI categories, achieving area under the receiver operating characteristic curve...

CONCLUSION: Higher TyG-related metabolic indices were associated with incident PE in this large prospective cohort. PhenoAgeAccel-related decomposition and genetic susceptibility analyses were exploratory and require external replication.

CONCLUSION: This study provides insights about the potential of simultaneous motor-cognitive training for improving motor capacities in older adults, even if its efficiency is not different to motor training. Furthermore, neither incorporated nor additional training seem to be the optimal modality. Future comparative studies are needed to draw firm conclusions.

Cellular senescence is a key driver of kidney aging, leading to functional decline and increased susceptibility to chronic kidney disease. While the senolytic combination of dasatinib and quercetin (D + Q) has shown promise in mitigating age-related pathologies, its long-term effects and underlying multi-level systemic mechanisms in the aging kidney remain poorly defined. Here, we systematically evaluated the long-term effects of D + Q in naturally aged mice using multi-omics approaches. We show...

Age-related decline in left ventricular (LV) diastolic function is a hallmark of cardiac aging and an early precursor to cardiovascular disease. While dyslipidemia is a known driver of coronary heart disease (CHD), the molecular pathways linking lipid metabolism to cardiac aging and subsequent CHD risk remain poorly understood. Furthermore, longitudinal lipidomic profiling of cardiac aging in large human populations has not been systematically conducted. Using an untargeted LC-MS, we repeatedly...

No abstract

Mutations in the GBA1 gene, which encodes the lysosomal glucocerebrosidase enzyme GCase, cause the lysosomal storage disorder Gaucher disease and represent the most common genetic risk factor for Parkinson's disease (PD). These mutations deplete lysosomal GCase activity and cause accumulation of GCase substrate, glucosylceramide, and its pathological metabolite, glucosylsphingosine. Impaired GCase activity then drives immune and neuronal dysfunction in Gaucher disease and promotes pathogenic...

The rapid expansion of plasma proteomic data and protein quantitative trait loci (pQTLs) provides an opportunity to identify genes that confer disease risk through their effect on plasma protein abundance. We conducted an Alzheimer's disease (AD) proteome-wide association study (PWAS) integrating publicly available plasma cis-pQTL data (1348 European American and 1385 African American genetically determined protein models) with AD dementia GWAS summary statistics. Whereas the African American...

Lateralization is a hallmark of brain organization, yet the structural basis underlying this phenomenon remains a critical, unresolved question in cognitive and systems neuroscience. In this study, we applied multivariate machine learning techniques to investigate variations of global brain asymmetry and their associations with cognitive functions, aging, and aging-related diseases, using large-scale datasets. Our findings revealed substantial and previously unknown structural differences...

Aging is intimately entangled with the reprogramming of metabolic pathways that coordinate energy production, biosynthesis, and molecular turnover. However, visualizing and understanding these metabolic underpinnings within their spatial and temporal contexts remains a major challenge. Metabolic imaging has emerged as a transformative approach that enables spatially resolved visualization of metabolic dynamics both at the molecular or cellular and organismal levels. In this review, we summarize...

Lateralization is a hallmark of brain organization, yet the structural basis underlying this phenomenon remains a critical, unresolved question in cognitive and systems neuroscience. In this study, we applied multivariate machine learning techniques to investigate variations of global brain asymmetry and their associations with cognitive functions, aging, and aging-related diseases, using large-scale datasets. Our findings revealed substantial and previously unknown structural differences...

The self-assembled monolayer (SAM) has driven the rapid increase in the power conversion efficiency (PCE) of perovskite solar cells (PSCs). However, the operation stability of these PSCs under real conditions continues to be challenging. We developed an SAM based on phthalocyanine, which has a structurally robust framework with chemically stable bonds that enhance photostability. Tetraphosphorylation further enables the firmly locked phthalocyanine at the interface, which improves thermal...

A synthetic cell can now grow and divide—but it’s still far from alive

Telomeres progressively shorten and accumulate damage with aging, and this contributes to cellular senescence and hematopoietic dysfunction. We previously showed that telomere dysfunction induces synthesis of telomeric noncoding RNAs required for activation of the telomeric DNA damage response (tDDR), a driver of senescence and inflammation. However, whether the tDDR causally impairs hematopoiesis remained unclear. Here we show in telomerase-deficient Terc^(-/-) mice, which recapitulate...

CONCLUSIONS: These findings provide novel evidence for the interactive effects of objective and subjective age, psychosocial resources, and cultural context on cognitive aging, highlighting the potential importance of age perceptions and social participation in cognitive aging.

CONCLUSIONS: The findings of this study demonstrate that adequate sleep duration and PA are crucial independent and synergistic protective factors against rapid frailty progression. These findings highlight that concurrently targeting both behaviors is a vital clinical strategy to mitigate severe frailty and promote healthy aging.