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Human brain vascular multi-omics elucidates disease-risk associations

3 weeks ago
Cerebrovascular dysfunction underlies many neurological disorders, yet how genetic variants in brain vascular cells drive disease risk remains unknown. We developed MultiVINE-seq to simultaneously profile RNA and chromatin accessibility in vascular, perivascular, and immune cells from 30 human brains. Mapping genome-wide association study (GWAS) data to our multi-omic atlas linked thousands of GWAS disease-risk variants to target cell types and genes, including 2,605 previously unmapped. We...
Madigan M Reid

The impact of ER<sup>UPR</sup> on mitochondrial integrity mediated by PDK4

3 weeks ago
ER and mitochondrial stress are often interconnected and considered major contributors to aging as well as neurodegeneration. Coordinated induction of ER^(UPR) and mito^(UPR) has been observed in diabetes and pulmonary disorders. However, in the context of aging and neurodegeneration, regulation of this intra-organellar crosstalk has remained relatively elusive. Here, we demonstrate that pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial protein, accumulates at the ER-mitochondrial contact...
Priyanka Mallick

A novel deep learning-based brain age prediction framework for routine clinical MRI scans

3 weeks ago
Physiological brain aging is associated with cognitive impairment and neuroanatomical changes. Brain age prediction of routine clinical 2D brain MRI scans were understudied and often unsuccessful. We developed a novel brain age prediction framework for clinical 2D T1-weighted MRI scans using a deep learning-based model trained with research grade 3D MRI scans mostly from publicly available datasets (N = 8681; age = 51.76 ± 21.74). Our model showed accurate and fast brain age prediction on...
Hyunwoong Kim

Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis

3 weeks ago
The accumulation of amyloid fibrils has been identified in tissues outside the brain, yet little is understood about the formation of extracerebral amyloidosis and its impact on organ aging. Here, we demonstrate that both transgenic Alzheimer's disease (AD) mice and naturally aging mice exhibit accumulated senescent bone marrow adipocytes (BMAds), accompanied by amyloid deposits. Senescent BMAds acquire a secretory phenotype, markedly increasing secretion of serum amyloid P component (SAP), also...
Surendra Kumar

HETEROGENEITY ANALYSIS OF ASSOCIATIONS INVOLVING THE LARGE SCALE ONLINE MINDCROWD SURVEY MEMORY TEST

3 weeks ago
Alzheimer's disease and related disorders (ADRD), as well as general age-related cognitive decline, are known to be multifactorial with heterogeneous etiologies. Identifying and accommodating heterogeneity in any one data set can be pursued using different analytical techniques, each with different assumptions or purposes. Whereas a great deal of research has explored clustering individuals of variables that exhibit greater similarity in some way, little research has explored evidence for...
Nivedita Bhadra

The impact of ER<sup>UPR</sup> on mitochondrial integrity mediated by PDK4

3 weeks ago
ER and mitochondrial stress are often interconnected and considered major contributors to aging as well as neurodegeneration. Coordinated induction of ER^(UPR) and mito^(UPR) has been observed in diabetes and pulmonary disorders. However, in the context of aging and neurodegeneration, regulation of this intra-organellar crosstalk has remained relatively elusive. Here, we demonstrate that pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial protein, accumulates at the ER-mitochondrial contact...
Priyanka Mallick

Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging

3 weeks ago
Mosaic loss of chromosome Y (mLOY) is the most common somatic mutation in hematopoietic cells of aging men and is linked to cancer risk and mortality. However, its relationship with treatment modalities remains unclear. In 348 prostate cancer patients at Juntendo University Hospital, local radiotherapy was associated with a higher prevalence of mLOY (OR = 2.55, 95% CI: 1.08-6.50, P = 0.04), whereas surgery and endocrine therapy were not. We then examined BioBank Japan data from over 30,000...
Takuro Kobayashi

Time-dependent catalytic activity in aging condensates

3 weeks ago
Biomolecular condensates are dynamic cellular compartments that concentrate proteins and enzymes to regulate biochemical reactions in time and space. While these condensates can enhance enzyme activity, how this function changes as condensates age remains poorly understood. Here, we design synthetic catalytic condensates that selectively recruit enzymes to investigate this temporal evolution. We show that catalytic condensates exhibit time-dependent activity: they initially accelerate enzymatic...
Wei Kang

A novel deep learning-based brain age prediction framework for routine clinical MRI scans

3 weeks ago
Physiological brain aging is associated with cognitive impairment and neuroanatomical changes. Brain age prediction of routine clinical 2D brain MRI scans were understudied and often unsuccessful. We developed a novel brain age prediction framework for clinical 2D T1-weighted MRI scans using a deep learning-based model trained with research grade 3D MRI scans mostly from publicly available datasets (N = 8681; age = 51.76 ± 21.74). Our model showed accurate and fast brain age prediction on...
Hyunwoong Kim