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Single-nucleus multi-omics identifies shared and distinct pathways in Pick's and Alzheimer's disease

2 weeks 1 day ago
The study of transcriptomic and epigenomic variations in neurodegenerative diseases, particularly tauopathies like Pick's disease (PiD) and Alzheimer's disease (AD), offers insights into their underlying regulatory mechanisms. Here, we identified critical regulatory changes driving disease progression, revealing potential therapeutic targets. Our comparative analyses uncovered disease-enriched noncoding regions and genome-wide transcription factor (TF) binding differences, linking them to target...
Zechuan Shi

iPEX enables micrometre-resolution deep spatial proteomics via tissue expansion

2 weeks 1 day ago
The number of spatial omics technologies being developed is increasing¹. However, a missing tool is one that can locate proteins in tissues in an untargeted manner at high spatial resolution and coverage. Here we present in situ imaging proteomics via expansion (iPEX), which integrates isotropic tissue magnification² with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging. iPEX provides scalable spatial resolution down to the micrometre scale and substantially...
Fengxiang Wang

circHERC1-A telomerase activator

2 weeks 1 day ago
Telomerase, crucial for maintaining telomere integrity and genomic stability, is typically silenced in somatic cells with advancing age. In this study, we identify circHERC1 as a regulator of telomerase reverse transcriptase (TERT) transcription. Specifically, circHERC1 binds to the TERT promoter, facilitating the recruitment of RNA polymerase II and c-Fos, thereby activating TERT expression. Notably, circHERC1 expression exhibits a decline with age, which correlates with reduced telomerase...
Yumeng Cui

Liver-directed AAV gene therapy in mice corrects glycogen storage disease type IX γ2

2 weeks 1 day ago
Glycogen storage disease (GSD) type IX γ2 is a rare inborn error of metabolism where a defect in glycogenolysis leads to the inability to break down glycogen in the liver. Patients with GSD IX γ2 develop hypoglycemia and advanced liver disease, placing them at risk for liver transplantation. This study evaluates the efficacy of liver-directed AAV gene therapy in a murine model of GSD IX γ2. Phkg2^(-/-) mice underwent treatment with AAV gene therapy (AAV9-LSP-mPhkg2, 5 × 10^(12) vg/kg,...
Rebecca A Gibson

Aging and immunity

2 weeks 1 day ago
Time marches endlessly on … but what does that mean for the immune system? Here, investigators discuss how aging impacts the immune response and how immune cells can shape the aging process, with broader implications for modifying immunity to improve not only longevity but also health span.
Christoph A Thaiss

Breaking the silence on late-life depression: uncovering the drivers of help-seeking in Turkiye's ageing population

2 weeks 1 day ago
CONCLUSION: The results achieved in this study indicate that among older adults experiencing depression, women, those with higher educational levels, and those with existing illnesses are more likely to seek psychological support. Based on these results, it is recommended to develop educational programs to raise societal awareness about the importance of psychological support and to inform health policies accordingly.
Uğur Ercan

Widespread neuronal hemokinin-1 expression in motor regions and its protective role in age-related impairment

2 weeks 1 day ago
Hemokinin-1 (HK-1) regulates several processes in the central and peripheral nervous systems, including musculoskeletal functions; however, its involvement in age-related motor coordination and muscle strength remains unknown. Therefore, these were investigated here with HK-1-deficient mice together with the expression patterns in the mouse and human motor coordination centers. Tac4 gene expression, encoding HK-1, was detected by RNAscope, and its age-dependent changes in the cerebellum and...
Dávid Vince Simon

Life-extending interventions do not necessarily result in compression of morbidity: a case example offering a robust statistical approach

2 weeks 1 day ago
Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting...
Deependra K Thapa