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Three-dimensional mapping of intact ovaries reveals the aging dynamics of the ovarian reserve

2 weeks ago
Female fertility depends on a finite pool of oocytes that depletes during aging^(1,2), yet the spatiotemporal dynamics of this depletion remain poorly understood. Traditional methods obscure the three-dimensional architecture of the ovary, limiting quantitative insights. Here we combine light-sheet microscopy, artificial intelligence-driven segmentation and mathematical modeling to map over 85,000 oocytes in whole ovaries across the reproductive lifespan in mouse. We find that newly activated...
Arturo D'Angelo

Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice

2 weeks ago
There is little understanding of how aging serves as the strongest risk factor for several neurodegenerative diseases. Microglia undergo age-related maladaptive changes, including increased inflammation, impaired debris clearance, and cellular senescence, yet specific mediators that regulate these processes remain unclear. The aged brain is rejuvenated by youth-associated plasma factors, including tissue inhibitor of metalloproteinases 2 (TIMP2), which we have shown acts on the extracellular...
Brittany M Hemmer

Preclinical evaluation of nitrated alpha-synuclein-specific CAR-Treg therapy in Parkinson's disease

2 weeks ago
Current evidence indicates that Parkinson's disease (PD) involves T cell-mediated inflammation, which plays a fundamental role in promoting neuroinflammation and neurodegeneration in patients and animal models. These T cells are specific to α-synuclein-derived antigens, including nitrated α-synuclein (NαSyn). Here, we sought to develop an experimental immunotherapy for PD based on the generation of regulatory T cells (Treg) specific to NαSyn, using the chimeric antigen receptor (CAR) technology....
Valentina Ugalde

Targeting the hallmarks of ageing: Pharmacological challenges and breakthroughs in CRISPR delivery systems and future prospects

2 weeks ago
CRISPR has emerged as a next-generation gene-editing tool with the potential to target the molecular pathways associated with ageing and related disorders. It functions through RNA-guided Cas nucleases, directing DNA cleavage and utilizing the native DNA repair machinery for genetic manipulations. Advances in CRISPR technology have significantly enhanced the precision and flexibility of techniques for genome editing. The enzyme Cas9's ability to cut DNA at exact site has revolutionized genome...
Sakshi Rathore

Targeting the hallmarks of ageing: Pharmacological challenges and breakthroughs in CRISPR delivery systems and future prospects

2 weeks ago
CRISPR has emerged as a next-generation gene-editing tool with the potential to target the molecular pathways associated with ageing and related disorders. It functions through RNA-guided Cas nucleases, directing DNA cleavage and utilizing the native DNA repair machinery for genetic manipulations. Advances in CRISPR technology have significantly enhanced the precision and flexibility of techniques for genome editing. The enzyme Cas9's ability to cut DNA at exact site has revolutionized genome...
Sakshi Rathore

The association between doubly labeled water- and accelerometer-measured physical activity, brain volume, and cognitive function in older adults with cardiometabolic or functional risks

2 weeks ago
Regular physical activity is beneficial for brain health. However, no research has explored whether physical activity level (PAL) assessed by the doubly labeled water method (PAL-DLW) is associated with brain volume and cognitive function. We investigated whether PAL-DLW, accelerometer-assessed PAL (PAL-Acc), and components of physical activity are associated with brain volume and cognitive function in older adults. We analyzed data from 49 participants with cardiometabolic or functional risks...
Mizuki Sudo

Age-associated inflammation is accompanied by JAK1-STAT1 signaling activation, megakaryocyte apoptosis, and enhanced thrombopoiesis in naturally aged mice

2 weeks ago
CONCLUSION: Age-associated inflammation is accompanied by activation of the IL6ST/JAK1-STAT1 signaling pathway, increased megakaryocyte apoptosis, and enhanced thrombopoiesis in aged mice. These findings suggest that inflammation-driven megakaryocyte remodeling may represent a compensatory mechanism for sustaining platelet production during aging and may contribute to the heightened thrombotic risk observed in older individuals.
Yixuan Xu

Prediction of mild cognitive impairment progression using time-sensitive multimodal biomarkers

2 weeks ago
Alzheimer's disease (AD) develops silently for years before symptoms emerge, making early identification of at-risk individuals essential for prevention trials and early intervention. We tested whether combining neurophysiological, imaging, and blood biomarkers improves prediction of progression to mild cognitive impairment (MCI) in cognitively unimpaired older adults with a family history of AD (n = 102; 31 progressors; mean follow-up of 5.9 years). Magnetoencephalography, magnetic resonance...
Jonathan Gallego-Rudolf

MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration

2 weeks ago
Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is...
Jason J Colasanti

Aging-associated increase of GATA4 levels in articular cartilage is linked to impaired regenerative capacity of chondrocytes and osteoarthritis

2 weeks ago
Although the causal association between aging and osteoarthritis (OA) has been documented, our understanding of the underlying mechanism remains incomplete. To define the regulatory molecules governing chondrocyte aging, we performed transcriptomic analysis of young and old human chondrocytes from healthy donors. The data predicted that GATA-binding protein 4 (GATA4) may play a key role in mediating the difference between young and old chondrocytes. Results from immunostaining and western blot...
Meagan J Makarczyk

Fully dry-processed electrodes for highly reversible aqueous zinc powder-based batteries

2 weeks ago
Aqueous zinc-ion batteries have advanced rapidly, but practical deployment is limited by excessive negative-to-positive (N/P) ratios (>50), decreasing the energy density. Zinc powder anodes can lower N/P, yet their high specific surface area accelerates parasitic reactions and shortens lifespan. Here we report a high-loading and highly reversible dry-processed zinc powder anode with a non-electrochemically driven solid-electrolyte interphase (SEI). The dry process retains a homogeneous...
Han Wu

Mitochondrial stress activates ELT-2-dependent lysosomal proteostasis to extend lifespan in C. elegans

2 weeks ago
Mild mitochondrial stress could extend lifespan across species, yet the underlying mechanism remains unclear. Here, we show that inhibition of mitochondrial respiration induces a sustained transcriptional program that enhances lysosomal proteolysis during aging in Caenorhabditis elegans. Mechanistically, this response is primarily regulated by the intestinal GATA transcription factor ELT-2, which retains high expression and directly binds to GATA motifs in the promoters of lysosomal protease...
Rendan Yang

Normative age-related changes in resting-state EEG alpha power and theta/alpha ratio across eyes-open and eyes-closed conditions

2 weeks ago
Resting-state electroencephalography (EEG) provides a sensitive measure of large-scale neural dynamics and has been widely used to characterize age-related changes in brain function. However, many prior studies have relied on relatively small samples or single-condition recordings, limiting the generalizability of findings. In this study, we investigated normative age-related trajectories of EEG spectral features across eyes-closed (EC) and eyes-open (EO) conditions in a large cohort of healthy...
Ye-Ji Park