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Science, Volume 390, Issue 6779, Page 1236-1236, December 2025.

A mix of Science’s most loved and most read items of the year

Cells in the guts of female mice respond to estrogen by increasing pain signaling, researchers find

Clean energy infrastructure is being deployed with unmatched scale and speed—and China is leading the way

Right-wing politician José Antonio Kast has promised to slash government spending

Ferroelectrics could bolster “flash” memory in AI data centers and autonomous robots

CONCLUSION: In healthy older adults, a single session of tDCS designed to modulate DAN and DN excitability concurrently improved gait speed in both single and dual-task walking, as well as working memory. These preliminary findings suggest that gait and working memory may be modifiable through neuromodulation approaches involving DAN and DN. Further studies are warranted to explore the relationship between gait, working memory, and these two brain networks using neuroimaging means.

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Synaptic loss is a hallmark of Alzheimer's disease (AD) but lacks robust blood-based biomarkers. We investigate growth-associated protein 43 (GAP-43), previously identified as a synaptic candidate in the cerebrospinal fluid (CSF). Postmortem proteomic profiling of brain-derived extracellular vesicles (n = 21) highlights GAP-43 as a central hub within synaptic protein networks co-depleted in AD and closely linked with proteins enriched in immune-, metabolic-, and synaptic-related modules. In two...

Glucagon-like peptide-1 (GLP-1) medicines are used for the treatment of type 2 diabetes (T2D) and obesity and reduce rates of cardiovascular disease, including stroke, in people with T2D. Substantial evidence from real-world data and clinical trials highlights the therapeutic potential of GLP-1 medicines for the treatment of neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Similarly, there is growing evidence for the potential utility of using GLP-1 medicines to reduce...

The prevalence of Alzheimer's disease neuropathological changes (ADNCs), the leading cause of cognitive impairment, remains uncertain. Recent blood-based biomarkers enable scalable assessment of ADNCs¹. Here we measured phosphorylated tau at threonine 217 in 11,486 plasma samples from a Norwegian population-based cohort of individuals over 57 years of age as a surrogate marker for ADNCs. The estimated prevalence of ADNCs increased with age, from less than 8% in people 58-69.9 years of age to...

Circulating metabolites can identify biochemical risk factors related to Alzheimer's disease (AD). We measured plasma metabolites in 1,068 participants of Caribbean Hispanic ancestry (250 patients with AD and 818 healthy controls) across 2 cohorts and analyzed their relationship with clinical AD, biomarker-supported AD and plasma biomarkers (P-tau181, P-tau217, P-tau231 and Aβ42:Aβ40). Amino acid metabolism pathways were enriched among metabolites associated with P-tau biomarkers, whereas sialic...

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Tau is a microtubule-associated cytoskeletal protein, which, when hyperphosphorylated and aggregated, can result in a myriad of different tauopathies, including Alzheimer's disease (AD). We previously showed that the principal component of senile plaques, amyloid beta (Aβ), is an antimicrobial peptide capable of binding and entrapping microbial pathogens. Here we show that tau is hyperphosphorylated in neurons in response to viral infection and can neutralize herpes simplex virus 1 (HSV-1)...

Aging is a natural physiological process that may be accompanied by pathological changes, particularly in the brain. Iron is an essential trace element supporting various physiological functions and maintaining cellular homeostasis. However, iron levels tend to increase in certain brain regions of older adults and are associated with the development of neurodegenerative diseases. Despite this association, the causal relationship between aging, iron accumulation, and neurodegenerative diseases...

Women's reproductive health plays a pivotal role in both longevity and the aging process. We conduct Mendelian randomization (MR) and observational analyses to investigate these relationships. Univariate MR analyses reveal that older age at first birth, later menarche, higher estradiol, and sex hormone-binding globulin (SHBG) increase longevity, while pre-eclampsia liability decreases longevity. Older ages at first birth and at first sexual intercourse are associated with lower DNAmGrimAgeAccel,...

Despite ample research on cognitive aging, it is still largely unknown whether cognition is organized in a distinct manner, with different cognitive domains and subcomponents interrelating with each other. It is also unknown whether this cognitive organization is stable or changes with increasing age. Following the PRISMA guidelines statement, we conducted a systematic review of multivariate studies of cognitive aging with the aim to identify a potential cognitive organization in healthy aging....

Senescence contributes to the pathology of abdominal aortic aneurysm (AAA); however, the regulation of senescence in AAA remains unclear. Here, we sought to determine the role of gasdermin-E (GSDME)-dependent non-canonical pyroptosis in AAA. GSDME-dependent non-canonical pyroptosis is activated in the lesioned vascular walls of mouse models and patients with AAA. GSDME deficiency inhibits vascular senescence and AAA progression. Combined analyses of single-cell RNA sequencing (scRNA-seq), bulk...

Hepatocellular carcinoma (HCC) is one of the most prevalent and malignant forms of primary liver cancer, with limited therapeutic options and a poor prognosis. Cellular senescence contributes to the progression of chronic liver disease while creating a microenvironment that supports tumor growth. This study aims to identify dual-purpose therapeutic targets for HCC treatment and cellular senescence intervention, potentially leading to more effective therapeutic strategies. Utilizing the AI-driven...

Accelerated biological aging (BA) is linked to adverse cardiovascular events, but its role in heart failure with preserved ejection fraction (HFpEF) remains unclear. We analyzed 1,727 HFpEF patients from RED-CARPET Study (ChiCTR2000039901), assessing BA using Klemera-Doubal and PhenoAge methods. During a median 4.9-year follow-up, 321 all-cause and 180 cardiovascular deaths occurred. After full adjustment, per 1-SD increase in BA acceleration showed significantly higher risk of all-cause...