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Silencing of the Metabolic Gene HKDC1 Is Associated With Aging and Neurodegeneration in Mice and Humans

5 hours 51 minutes ago
Increased life expectancy brought about by improved healthcare and lifestyle has heightened the challenge of neurodegenerative disorders like Alzheimer's disease (AD) and other age-related disorders. Neurodegeneration is known to be accompanied by loss of memory, changes in brain morphology, and neuroinflammation, and multiple factors contribute to the progression and pathogenesis of the condition. Of these factors, metabolic dysregulation is known to influence the process, but the precise...
Zeenat Farooq

Silencing of the Metabolic Gene HKDC1 Is Associated With Aging and Neurodegeneration in Mice and Humans

5 hours 51 minutes ago
Increased life expectancy brought about by improved healthcare and lifestyle has heightened the challenge of neurodegenerative disorders like Alzheimer's disease (AD) and other age-related disorders. Neurodegeneration is known to be accompanied by loss of memory, changes in brain morphology, and neuroinflammation, and multiple factors contribute to the progression and pathogenesis of the condition. Of these factors, metabolic dysregulation is known to influence the process, but the precise...
Zeenat Farooq

Select Small Non-Coding RNAs Are Determinants of Survival in Older Adults

5 hours 51 minutes ago
To investigate the relevance of small RNAs to human longevity, we pursued three goals: (a) to validate epigenetic (small RNA) factors underlying survival of older adults, (b) to develop and validate prediction models of survival for potential clinical application, and (c) to identify plausible druggable targets prolonging longevity. We evaluated 828 small non-coding RNAs-687 microRNAs (miRNAs) and 141 piwi-interacting RNAs (piRNAs)-in baseline plasma from 1271 community-dwelling older adults (≥...
Virginia Byers Kraus

A lineage-specific selective autophagy receptor module mediates P-body turnover

1 day 5 hours ago
Processing bodies (P-bodies) are conserved ribonucleoprotein granules central to RNA metabolism across eukaryotes. Although the mechanisms underlying their assembly are well understood, the pathways governing their selective turnover remain unclear. Here, we identify the conserved decapping proteins Enhancer of mRNA decapping 4 (EDC4) and decapping protein 1 (DCP1) as a selective autophagy receptor pair responsible for P-body turnover in the model plant Marchantia polymorpha. MpEDC4 engages ATG8...
Alibek Abdrakhmanov

DNA-PK-mediated phosphorylation of STAT6 establishes a non-canonical type 2 immunity axis to prevent macrophage senescence

1 day 5 hours ago
Macrophage senescence drives inflammaging, a chronic, age-related inflammation. To date, the protective mechanisms against inflammaging are poorly defined. Here, we identify DNA-PK-mediated phosphorylation of murine STAT6 at serine 807 (Ser807) as a crucial post-translational modification for preventing macrophage senescence. Ser807 phosphorylation blocks STAT6 ubiquitination-mediated degradation and promotes STAT6 partnering with PU.1 to activate DNA repair genes. Macrophages lacking Ser807...
Zhao Zhou

Metabolic quiescence of naive-like memory T cells precedes and maintains antigen-specific T cell memory

1 day 5 hours ago
Metabolic activity shapes cell fate but remains challenging to capture in vivo with high resolution. Here we performed longitudinal metabolic and phenotypic profiling of human antigen-specific CD8^(+) T cells after yellow fever vaccination using flow cytometry and single-cell RNA sequencing. As assessed by protein translation rates, CD8^(+) T cells upregulated glycolysis to fuel anabolic needs for proliferation but predominantly used oxidative phosphorylation for energy production during the...
Sina Frischholz

Disrupted drainage in the aging brain: Meningeal lymphatic decline as a convergent axis of vulnerability

1 day 5 hours ago
The aging brain depends on coordinated fluid transport, immune surveillance, and clearance of metabolic byproducts to preserve cognitive and physiological homeostasis. While peripheral lymphatic decline is well established, growing evidence implicates brain-draining lymphatic pathways, particularly meningeal lymphatic vessels and their downstream drainage to deep cervical lymph nodes, as an aging-sensitive axis that intersects with neuroinflammation and neurodegenerative vulnerability. Here, we...
M Elyse Moore

iCLAP: an innovative method for integrable co-detection of low-abundance antigens with high-plex immunostaining

1 day 5 hours ago
Multiplexed protein imaging enables spatial analysis of complex tissues, but detecting proteins expressed at low levels remains challenging, particularly in widely available formalin-fixed, paraffin-embedded (FFPE) specimens. Many biologically important regulators-including senescence markers, transcription factors, and secreted proteins-are therefore difficult to study in situ using existing high-plex methods. Here we show that integrable Co-detection of Low-Abundant Proteins (iCLAP) enables...
Fan Wu

Biological age and immunosenescence in Colombian centenarians

1 day 5 hours ago
Biological aging and immunosenescence are central to longevity, yet their interplay in centenarians remains unclear. We conducted a cross-sectional study in 160 Colombian centenarians to examine associations between biological age (PhenoAge), immunosenescence and age-related clinical variables. Cytokine profiling (n = 114) and lymphocyte immunophenotyping (n = 42) were assessed. It was observed that better QoL and well-being were significantly associated with lower biological age, while...
Juan-Manuel Anaya

Aging increases visual dependency and disrupts sensory strategies in upright standing

1 day 5 hours ago
Postural control depends on the integration of visual and proprioceptive inputs, yet how aging modifies this sensorimotor integration in upright standing remains unclear. We examined age-related differences in postural responses to visual and proprioceptive disturbances during upright standing by applying (i) bilateral Achilles or tibialis anterior tendon vibration and (ii) and simulated forward or backward self-motion in a virtual environment. Eighteen young [22.8 (1.6)yr] and eighteen old...
Christophe Barbanchon

Transsaccadic working memory in healthy ageing and neurodegenerative disease

1 day 5 hours ago
The brain continuously integrates rapidly changing visual input across eye movements to maintain stable perception, yet the precise mechanisms underpinning dynamic working memory and how these break down in brain diseases remain unclear. We developed a novel eye-tracking paradigm and computational models to investigate how spatial and colour information are updated across saccades in the human brain. Our findings reveal that saccades selectively impair spatial but not colour memory....
Sijia Zhao

Non-visual light modulates behavioral memory and gene expression in <em>Caenorhabditis elegans</em>

1 day 5 hours ago
Visible light influences a range of physiological processes, yet how animals respond to it independently of the visual system remains largely unknown. Here, we uncover a previously undescribed light-induced transcriptional pathway that modulates behavioral plasticity in Caenorhabditis elegans, a roundworm without eyes. We demonstrate that ambient visible light or controlled-intensity visible-spectrum LED activates an effector gene cyp-14A5 in non-neuronal tissues through the bZIP transcription...
Zhijian Ji

Transsaccadic working memory in healthy ageing and neurodegenerative disease

1 day 5 hours ago
The brain continuously integrates rapidly changing visual input across eye movements to maintain stable perception, yet the precise mechanisms underpinning dynamic working memory and how these break down in brain diseases remain unclear. We developed a novel eye-tracking paradigm and computational models to investigate how spatial and colour information are updated across saccades in the human brain. Our findings reveal that saccades selectively impair spatial but not colour memory....
Sijia Zhao

Genome-wide association study of frailty and integrative functional analysis to elucidate its relationship with aging

1 day 5 hours ago
Frailty is a clinically recognizable condition of vulnerability with aging, leading to adverse health outcomes. Previous GWASs on frailty have identified 59 susceptibility loci, although the underlying mechanisms remain unclear. We investigated the genetic determinants of frailty and biological relationship between frailty and aging genes in 14,664 middle-aged and elderly Korean participants. We performed cohort-based (KoGES and KNHANES) meta-analysis of GWAS and candidate gene approach focusing...
Yujin Kwak