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Diverse mitochondrial stresses activate PINK1-PRKN/parkin mitophagy by a unified mechanism

21 hours 32 minutes ago
Mutations in PINK1 and PRKN/parkin are the leading recessive causes of Parkinson disease (PD). Together PINK1 and PRKN form a mitophagy pathway for clearing damaged mitochondria from the cell. It was unclear, however, whether diverse forms of mitochondrial damage activate the PINK1-PRKN pathway through a unified mechanism. Recently, we demonstrated that loss of mitochondrial membrane potential (MMP) leads to the stabilization and activation of PINK1 under a wide range of mitochondrial stressors,...
Julia A Thayer

RF-SIRF reveals a replication stress-specific epigenetic code by spatio-temporal mapping of reversed forks

21 hours 32 minutes ago
DNA replication stress responses are guardians of genomic stability critical during development, hematopoiesis, cancer therapy response, aging and disease suppression. Central to these responses are reversed forks (RF), which are distinct four-way DNA structures formed during DNA replication stalling to protect against toxic DNA lesions. Historically, RF detection relies on specialized electron microscopy, precluding studies within their native cellular context. By harnessing intrinsic...
Sunetra Roy

Age-related directional asymmetry in the rod-and-frame test

21 hours 32 minutes ago
CONCLUSIONS: We propose that aging affects RFT performance through two dissociable mechanisms. A general decline in multisensory integration increases overall errors symmetrically across tilt angles. The clockwise-specific asymmetry, by contrast, may reflect age-related changes in lateralized visuospatial attention-specifically, the well-documented rightward attentional shift that accompanies healthy aging-which differentially affects the weighting of visual cues for clockwise vs....
Michał Adamski

Telomere dysfunction is associated with exacerbated intermittent hypoxia-induced cognitive deficits and nerve damage

21 hours 32 minutes ago
Cognitive impairment associated with obstructive sleep apnea (OSA) is more prevalent and severe in the elderly, possibly due to age-related increases in neuronal susceptibility to intermittent hypoxia (IH). As telomere dysfunction is a key driver of cellular aging, this study aimed to characterize the interaction between telomere dysfunction and IH, and to explore the associated molecular alterations. Using telomere-damaged PC12 cells and G3 Tert^(-/-) progeria mice exposed to IH, we assessed...
Ying Guo

Serum proteomics reveals biomarkers for diagnosis, stratification, and mechanistic insights into cerebral microbleeds

21 hours 32 minutes ago
OBJECTIVE: Cerebral microbleeds (CMBs) are small vascular lesions detectable on MRI and are associated with increased stroke risk and cognitive decline. However, imaging-based diagnosis is limited by cost and accessibility. This study aimed to identify serum protein biomarkers for early CMB diagnosis and to elucidate molecular mechanisms underlying CMB subtypes.
Wu-Meng Yin

Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials

1 day 21 hours ago
BACKGROUND: Evidence, including animal, clinical, and real-world studies in individuals with type 2 diabetes and/or obesity, suggests reduced risk of dementia and Alzheimer's disease after GLP-1 receptor agonist exposure. The evoke and evoke+ trials aimed to investigate the efficacy and safety of oral semaglutide in individuals with early Alzheimer's disease.
Jeffrey L Cummings

Therapeutic efficacy of engineered exosomes in Alzheimer's disease: A systematic review and meta-analysis of preclinical animal models

1 day 21 hours ago
Engineered exosomes are modified extracellular vesicles designed to enhance targeting and cargo delivery, and they have been proposed as a therapeutic strategy for Alzheimer's disease. We systematically reviewed preclinical animal studies evaluating engineered exosomes, synthesized evidence from comparisons with disease models and with natural exosomes, and reported the study in accordance with the PRISMA 2020 checklist. Outcomes included spatial learning and memory assessed by the Morris water...
An Li

Hallmarks of healthy cognitive aging: inter-individual differences in aging trajectories

1 day 21 hours ago
Cognitive aging is a highly heterogeneous process, with some individuals preserving stable cognitive performance across the lifespan while others exhibiting pronounced decline. This marked interindividual variability indicates that chronological age alone is a poor predictor of cognitive health. Rather than reflecting uniform degeneration, cognitive aging emerges from divergent biological trajectories spanning molecular, cellular, and network levels. In this review, we synthesize emerging...
Djoher Nora Abrous

Epigallocatechin gallate mitigates oxidative stress-induced transient senescence and injury by preserving mitochondrial integrity and restoring redox-inflammatory homeostasis in murine macrophages

1 day 21 hours ago
Macrophages serve as major defenders against pathogens, playing a crucial role in the initiation and modulation of immune responses. Age-related decline in macrophage functions is attributed to a complex network of cellular senescence and immunosenescence. The onset of cellular senescence is often a consequence of sustained oxidative stress, which is worsened by immunosenescence. Green tea catechin, epigallocatechin gallate (EGCG), has emerged as a promising candidate for promoting healthy aging...
Ravi Kumar