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Steve Gschmeissner’s electron microscope image of liver cholesterol won a Wellcome Photography Prize this year

The renin-angiotensin system (RAS), an important regulator of body fluid and cardiovascular homeostasis, is gradually implicated in the pathogenesis of neurological diseases due to its dysregulation. In addition to their traditional functions, components of the RAS, especially angiotensin-II (Ang-II), enhance neuroinflammation, oxidative stress, and neuronal injury. Ang-II exacerbates blood-brain barrier (BBB) disruption, promotes glial activation, and contributes to neurodegeneration via the...

Cerebrospinal fluid (CSF) α-synuclein (α-syn) seed amplification assays (SAAs) can detect Lewy body pathology (LBP) with high accuracy but are invasive and costly. To address these challenges, this study evaluated a two-step workflow combining prescreening via smell-function testing with confirmatory CSF α-syn SAA testing only in individuals with reduced smell, for predicting postmortem LBP status. Among 358 autopsied participants, the two-step workflow predicted brain LBP with high accuracy...

Leucine-rich repeat kinase 2 (LRRK2) is an essential regulator in cellular signaling and a major contributor to Parkinson's disease (PD) pathogenesis. 14-3-3 proteins are critical modulators of LRRK2 activity, yet the structural basis of their interaction has remained unclear. Here, we present the cryo-electron microscopy structure of the LRRK2:14-3-3(2) autoinhibitory complex, revealing how a 14-3-3 dimer stabilizes an autoinhibited LRRK2 monomer through dual-site anchoring. The dimer engages...

The three-dimensional (3D) genome structure is essential for gene regulation and various genomic functions. CTCF plays a key role in organizing Topologically Associated Domains (TADs) and promoter-enhancer loops, contributing to proper cell differentiation and development. Although CTCF binds the genome with high sequence specificity, its binding sites are dynamically regulated during development, and aberrant CTCF binding is linked to diseases such as cancer and neurological disorders, and...

State-of-the-art membranes derived from polymers of intrinsic microporosity offer promising alternatives to energy-intensive, thermally driven separation techniques but often suffer from reduced performance under condensable gases or physical aging. Here, extrinsically microporous polymer membranes (EMPMs) are introduced as a distinct class of microporous membranes, fabricated from perfluorinated aryl-ether-free aromatic polymers via defluorination-induced thermal cross-linking. This process...

Multi-organ biological aging clocks derived from clinical phenotypes and neuroimaging data have emerged as valuable tools for studying human aging and disease. Plasma proteomics provides an additional molecular dimension to enrich these clocks. In this study, I developed 11 multi-organ proteome-based biological age gaps (ProtBAGs) using 2,448 plasma proteins from 43,498 participants in the UK Biobank. Here I highlight methodological and clinical considerations for developing and using these...

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Older adults are the primary population for cell-based therapies for age-related diseases, but the efficacy of administering autologous mesenchymal stem cells (MSCs) is impaired due to biological aging. In the present study, we cultured aging adipose (AD)-derived MSCs from > 65-year-old donors on extracellular matrix (ECM) synthesized by human amniotic fluid-derived pluripotent stem cells (ECM Plus) versus tissue culture plastic (TCP) and hypothesized that ECM Plus provided an ideal "young"...

This systematic review aims to investigate the moderating effects of cognitive reserve (CR) on the relationships between cognitive function and multimodal Alzheimer's disease (AD)-signatured brain changes, measured by positron emission tomography (PET), structural magnetic resonance imaging (sMRI) and functional MRI (fMRI). Through a comprehensive search of PubMed, Scopus, and Web of Science, we identified 55 eligible studies examining the moderating effect of CR on the relationship between...

Accumulation of amyloid-β (Aβ) peptides and hyperphosphorylated tau proteins in the hippocampus triggers cognitive memory decline in Alzheimer's disease (AD). The incidence and mortality of sporadic AD were tightly associated with diabetes and hyperlipidemia, while the exact linked molecular mechanism is uncertain. Here, the present investigation identified significantly elevated serum Kallistatin levels in AD patients concomitant with hyperglycemia and hypertriglyceridemia, suggesting potential...

Aging is a process of gradual decline in physical and cognitive function and is a major risk factor for mortality. Despite the increasing number of relevant studies, the mechanisms regulating the aging process have not been fully elucidated. Genetic factors have long been recognized as key factors in controlling the rate of aging. Testes-specific protease 50 (TSP50) has been shown to be involved in the regulation of embryonic development and intestinal homeostasis, but its role in the regulation...

A physically active lifestyle benefits cellular aging, however the mechanisms linking physical activity (PA) with longevity remain unclear. PA is associated with longer telomere length (TL), while shorter TL has been associated with increased cellular aging. Some research suggests increased levels of inflammatory markers, such as C-reactive protein (CRP), are associated with telomere dysfunction. We tested the hypothesis that CRP levels mediate the association between PA and TL. Using data from...

Microglia are resident immune cells of the brain and are implicated in the etiology of Alzheimer's disease (AD) and other diseases. Yet the cellular and molecular processes regulating their function throughout the course of the disease are poorly understood. Here, we present a transcriptional analysis of primary microglia from 189 human postmortem brains, including 58 healthy aging individuals and 131 with a range of disease phenotypes, such as 63 patients representing the full clinical and...

There is increasing evidence to suggest that vascular dysfunction can contribute to cognitive decline in ageing and dementia. This dysfunction can take the form of a reduction of cerebral blood flow (CBF), a loss of blood-brain barrier (BBB) function or a combination of the two. Indeed, CBF and BBB changes may be causally linked, although this possible causality and its directionality are understudied. Appreciation of the role of vascular dysfunction in initiating cognitive decline in ageing and...

Microglia are resident immune cells of the brain and are implicated in the etiology of Alzheimer's disease (AD) and other diseases. Yet the cellular and molecular processes regulating their function throughout the course of the disease are poorly understood. Here, we present a transcriptional analysis of primary microglia from 189 human postmortem brains, including 58 healthy aging individuals and 131 with a range of disease phenotypes, such as 63 patients representing the full clinical and...

The effects of calorie restriction (CR) on age-related epigenetic modifications have recently been exposed, yet there is a road ahead in explaining the effects of CR on the epigenetic regulations. Although the exact mechanism(s) underlying the beneficial effects of CR on healthy brain aging is still unclear, increasing evidence suggests that epigenetic modifications are promising regulators that may be involved in this phenomenon. Here, we assessed the long-term effects of two different types of...

CONCLUSION: From 1992 to 2021, the global burden of varicella zoster among adults aged 65 and older has changed significantly. The ASIR of varicella and herpes zoster increased, but ASDR decreased. Despite the notable advancement in health equity across countries, the burden persists disproportionately among populations in low-SDI regions.

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BACKGROUND: Advancing age is the number one risk factor for cognitive decline and dementia, making cognitive aging a concern for the nearly half of Veterans who are age 65 and older. There has been a growing appreciation for the value of nonpharmacological lifestyle interventions in dementia risk reduction, including consistently exercising, eating a healthy diet, getting sufficient sleep, socializing, and engaging in cognitively stimulating activities. The 12-week Aging Well through Interaction...