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Cellular senescence is a state of permanent loss of proliferative capacity. Therefore, cells that reach a senescent state prevent tumor initiation, acting as an anti-tumor mechanism. However, despite not being proliferative, senescent cells have high secretory activity, constituting the Senescence-Associated Secretory Phenotype (SASP). SASP includes thousands of soluble molecules and extracellular vesicles, through which senescent cells can affect other cells and the extracellular matrix. In...

Following the demographic shift towards an ageing population over the past century, particularly in developed countries, the concept of healthspan has gained increasing acceptance as a key framework for understanding the drivers of healthy ageing. Accordingly, long-lived individuals, such as nonagenarians and centenarians, who remain free from chronic diseases, provide a valuable model to investigate the complex interplay of biological, genetic, and environmental factors that contribute to...

Previous studies have indicated increased dementia risk associated with fine particulate matter (PM(2.5)) exposure; however, the findings are inconsistent. In this systematic review, we assessed the association between long-term PM(2.5) exposure and dementia outcomes using the Burden of Proof meta-analytic framework, which relaxes log-linear assumptions to better characterize relative risk functions and quantify unexplained between-study heterogeneity (PROSPERO, ID CRD42023421869). Here we...

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Previous studies have indicated increased dementia risk associated with fine particulate matter (PM(2.5)) exposure; however, the findings are inconsistent. In this systematic review, we assessed the association between long-term PM(2.5) exposure and dementia outcomes using the Burden of Proof meta-analytic framework, which relaxes log-linear assumptions to better characterize relative risk functions and quantify unexplained between-study heterogeneity (PROSPERO, ID CRD42023421869). Here we...

Prohibitins are a highly conserved family of proteins that have been implicated in a variety of functions including mitochondrial stress signalling and housekeeping, cell cycle progression, apoptosis, lifespan regulation and many others. The human prohibitins prohibitin 1 and prohibitin 2 have been proposed to act as scaffolds within the mitochondrial inner membrane, but their molecular organization has remained elusive. Here we determined the molecular organization of the human prohibitin...

Institute of Museum and Library Services now run by Department of Labor as part of proposed dismantling

Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially for assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal fluid (CSF) samples from 136 participants in the Alzheimer's Disease Neuroimaging Initiative using more than 6,000 proteins. We apply machine learning to predict AD pathological stages defined by amyloid and tau positron emission...

CONCLUSIONS: This study highlights common neural targets in MCI, AD, and bvFTD and their link with cognitive impairment, emphasizing the value of LSM within a transdiagnostic approach to neurodegenerative diseases.

Neutrophils secrete a variety of mediators throughout their lifespan but are mostly associated with pro-inflammatory functions. In this issue of Cell, Hsu et al. describe a new class of extracellular vesicles produced solely by aged neutrophils that elicit anti-inflammatory effects that extend beyond neutrophil lifespan.

The skeleton is one of the most structurally and compositionally diverse organ systems in the human body, depending on unique cellular dynamisms. Here, we integrate prospective isolation of human skeletal stem cells (hSSCs; CD45^(-)CD235a^(-)TIE2^(-)CD31^(-)CD146^(-)PDPN^(+)CD73^(+)CD164^(+)) from ten skeletal sites with functional assays and single-cell RNA sequencing (scRNA-seq) analysis to identify chondrogenic, osteogenic, stromal, and fibrogenic subtypes of hSSCs during development and...

As the population ages, problems pertaining to health and life expectancy due to the aging heart have become increasingly prominent. The gut microbiota has become a potential therapeutic target in several diseases, including cardiovascular diseases. Current studies on the roles of the gut microbiota in the cardiovascular system have focused mainly on cardiovascular diseases; therefore, the effects of the gut microbiota on the natural aging of myocardial tissue remain unclear. The present study...

CONCLUSION: The adoption of mobile health apps must be prioritized to assist individuals with dementia and their caregivers in low income countries. Future apps should focus on improving engagement and involving medical experts in development to increase credibility and utilization across socioeconomic levels and healthcare systems.

Aging is associated with increased variability and dysregulation of the immune system. We performed a system-level analysis of serum cytokines in a longitudinal cohort of 133 healthy individuals over 9 y. We found that cancer incidence is a major contributor to increased cytokine abundance variability. Circulating cytokines increase up to 4 y before a cancer diagnosis in subjects with age over 80 y. We also analyzed cytokine expression in 10 types of early-stage cancers from The Cancer Genome...

Decreased nicotinamide adenine dinucleotide (oxidized form) (NAD^(+)) levels are reportedly associated with several aging-related disorders. Thus, supplementation with NAD^(+) precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), exhibits beneficial effects against these disorders. However, the in vivo metabolic pathways of NMN and NR remain to be elucidated. In this study, we comprehensively analyzed the fate of orally and intravenously administered NMN and NR in...

Survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD), an alloimmune fibrotic process leading to death or retransplantation after a median of 6 years. Immunosuppression fails to prevent CLAD, suggesting the existence of drug-resistant alloimmune pathways. We used time-of-flight mass cytometry to identify cells enriched in the bronchoalveolar lavage of patients with subsequent acute lung allograft dysfunction (ALAD), a risk factor for CLAD. We show that...

Vascular cognitive impairment (VCI) is a leading cause of age-related cognitive decline, driven by cerebrovascular dysfunction and cerebral small vessel disease (CSVD). Emerging evidence suggests that cerebromicrovascular endothelial senescence plays an important role in the pathogenesis of VCI by promoting cerebral blood flow dysregulation, neurovascular uncoupling, blood-brain barrier (BBB) disruption, and the development of cerebral microhemorrhages (CMHs). This review explores the concept of...

Emerging evidence has unveiled heterogeneity in phenotypic and transcriptional alterations at the single-cell level during oxidative stress and senescence. Despite the pivotal roles of cellular metabolism, a comprehensive elucidation of metabolomic heterogeneity in cells and its connection with cellular oxidative and senescent status remains elusive. By integrating single-cell live imaging with mass spectrometry (SCLIMS), we establish a cross-modality technique capturing both metabolome and...

Memory is a crucial cognitive function that deteriorates with age. However, this ability is normally assessed using cognitive tests instead of the architecture of brain networks. Here, we use reservoir computing, a recurrent neural network computing paradigm, to assess the linear memory capacities of neural-network reservoirs extracted from brain anatomical connectivity data in a lifespan cohort of 636 individuals. The computational memory capacity emerges as a robust marker of aging, being...

Mitochondria are multifunctional organelles that are important for many different cellular processes, including energy production and biosynthesis of fatty acids, haem and iron-sulfur clusters. Mitochondrial dysfunction leads to a disruption in these processes, the generation of excessive reactive oxygen species, and the activation of inflammatory and cell death pathways. The consequences of mitochondrial dysfunction are particularly harmful in energy-demanding organs such as the heart. Loss of...