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MRI-based multi-organ clocks for healthy aging and disease assessment

1 month 2 weeks ago
Biological aging clocks across organ systems and tissues have advanced understanding of human aging and disease. In this study, we expand this framework to develop seven magnetic resonance imaging-based multi-organ biological age gaps (MRIBAGs), including the brain, heart, liver, adipose tissue, spleen, kidney and pancreas. Using data from 313,645 individuals curated by the MULTI Consortium, we link the seven MRIBAGs to 2,923 plasma proteins, 327 metabolites and 6,477,810 common genetic...
MULTI Consortium

Parkinsonism disrupts the balance between excitatory and inhibitory activity within the primary motor cortex during movement

1 month 2 weeks ago
Parkinson's disease (PD) has been associated with alterations in neuronal activity in the basal ganglia-thalamocortical (BGTC) network. Previous studies have suggested that cortical disinhibition is a feature of PD, but there has been little direct evidence of the changes in cortical neuronal spiking activity to support this hypothesis. To test the hypothesis that activity in the motor cortex is enhanced in PD, we investigated the effects of parkinsonism on movement-related neuronal activity in...
Biswaranjan Mohanty

Decreased DNA methyltransferase 1 level in blood cells in Parkinson's disease

1 month 2 weeks ago
Parkinson's disease (PD) is a most common neurodegenerative disorder caused by genetic, epigenetic, and environmental factors. DNA methylation, regulated by DNA methyltransferases (DNMTs) is the key epigenetic modification playing an important role in gene expression regulation. Oligomeric alpha-synuclein - a major neurotoxic agent in PD - could sequester DNMT1 from the cell nucleus to the cytoplasm leading to global DNA hypomethylation. Here we evaluated DNMT1 expression (mRNA, protein),...
A O Lavrinova

Dynamic network reconfiguration in Parkinson's disease: associations with cognition and transcriptional signatures

1 month 2 weeks ago
Parkinson's disease (PD) is being increasingly recognized for its complex clinical symptoms, including cognitive impairment, which are linked to dynamic changes in brain network configuration and genetic susceptibility. However, the time-varying patterns of network reconfiguration in patients with PD and their relationship with gene expression profiles and cognitive function remain unclear. To address this gap, we analyzed modular variability (MV) in time-varying brain networks-comparing group...
Qiane Yu

Increased nucleotide metabolism alleviates Alzheimer's disease pathology

1 month 2 weeks ago
Genetic information in cells flows from DNA to RNA to proteins, which form molecular machines. During normal ageing, cell intrinsic and environmental factors alter this flow of information by damaging DNA in cells, including postmitotic neurons. Damage to DNA is associated with age-related neurodegenerative diseases such as Alzheimer's disease (AD). We previously reported an increase in DNA repair mechanisms in a fly model of AD. However, the causal mechanisms underlying somatic mutations in AD...
Yizhou Yu

Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel

1 month 2 weeks ago
Sortilin (SORT1) is a lipoprotein receptor that shows genome-wide association with hypercholesterolaemia, explained by its ability to control hepatic output of lipoproteins. Although SORT1 also shows genome-wide association with Alzheimer disease and frontotemporal lobe dementia, the most prevalent forms of age-related dementias, sortilin's contribution to human brain lipid metabolism and health remains unclear. Here we show that sortilin mediates neuronal uptake of polyunsaturated fatty acids...
Anna K Greda

Differential synaptic depression mediates the therapeutic effect of deep brain stimulation

1 month 2 weeks ago
Deep brain stimulation (DBS) effectively treats drug-resistant neurological and psychiatric disorders, yet its mechanisms remain unclear. Here we show that high-frequency DBS of the subthalamic nucleus (STN), a common target for Parkinson's disease (PD), activates afferent axons while inhibiting STN neurons. These contrasting presynaptic and postsynaptic effects arise from a decrease in local neurotransmitter release with a larger decrease in glutamate than GABA, shifting the...
Jicheng Li

MRI-based multi-organ clocks for healthy aging and disease assessment

1 month 2 weeks ago
Biological aging clocks across organ systems and tissues have advanced understanding of human aging and disease. In this study, we expand this framework to develop seven magnetic resonance imaging-based multi-organ biological age gaps (MRIBAGs), including the brain, heart, liver, adipose tissue, spleen, kidney and pancreas. Using data from 313,645 individuals curated by the MULTI Consortium, we link the seven MRIBAGs to 2,923 plasma proteins, 327 metabolites and 6,477,810 common genetic...
MULTI Consortium

Global mean sea level over the past 4.5 million years

1 month 2 weeks ago
Science, Volume 390, Issue 6770, October 2025.
Peter U. Clark, Jeremy D. Shakun, Yair Rosenthal, David Pollard, Steven W. Hostetler, Peter Köhler, Patrick J. Bartlein, Jonathan M. Gregory, Chenyu Zhu, Daniel P. Schrag, Zhengyu Liu, Nicklas G. Pisias