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Tremor is a common symptom in movement disorders such as Parkinson disease and essential tremor. While both conditions benefit from deep brain stimulation (DBS), the neural substrates underlying different tremor types and their treatment remain poorly defined. Here, we use DBS network mapping in multiple patient cohorts to investigate whether rest vs. action tremor respond to stimulation of the same or distinct subnetworks within the primary motor cortex. Building on recent functional...

Aging affects us all, but we still do not know how the process evolves or if we can modulate its pace. This issue of PLOS Biology presents a Collection of articles that explores different aspects of aging, discussing what challenges still need to be overcome.

Intermuscular fat infiltration driven by fibro-adipogenic progenitors contributes to the irreversible progression of sarcopenia and reflects a fate shift associated with altered calcium signaling. Using FAP-based adipogenesis models, structural and biochemical analyses, transcriptomic profiling, and in vivo drug exposure studies, we found that Ca^(2+) influx dyshomeostasis promotes adipogenic commitment by triggering calmodulin remodeling, dissociation of the KCNQ1-CaM-FTO complex, nuclear...

The amyloid precursor protein (APP) is associated with Alzheimer's disease. Appl is the single Drosophila APP ortholog and is expressed in all neurons throughout development. Appl was previously shown to cell-autonomously modulate axon outgrowth in the mushroom bodies (MBs), the fly olfactory memory center. However, we found that Appld, the only reported null allele, affects the normal function of vnd, the gene just proximal to Appl. To decipher developmental and memory defects specifically due...

Our post-GWAS functional analysis revealed that cathepsin L (CTSL) is an upstream regulator of CUX1, and it induces p16^(INK4a)-dependent and atherosclerosis-associated senescence by indirectly activating CUX1 transcription in a process that requires its proteolytic activity. This suggests an unidentified transcription regulator between CTSL and CUX1, and CTSL-mediated cleavage of this regulator could transcribe CUX1, inducing senescence. Here, in search of this transcriptional regulator, we...

Aging is a global issue that affects human health and increases disease risk. The traditional concept of the "age gap (AG)," defined as the difference between estimated biological age and an individual's chronological age, has been used for self-monitoring the risk of age-related diseases. However, the current AG does not account for the stratified aging patterns across different stages of chronological age, which may lead to biased or paradoxical interpretations of aging acceleration. To...

CONCLUSION: This study identifies a novel pathological mechanism in age-related MCI: the nuclear accumulation of PANK4 in hippocampal exacerbates cuproptosis susceptibility by specifically impairing ATP7B-dependent copper efflux, leading to copper overload. Astrocyte-specific PANK4 ablation mitigates these effects, highlighting PANK4 as a potential therapeutic target for preventing or treating age-associated cognitive decline.

INTRODUCTION: Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration, neuroinflammation, and emerging evidence of gut microbiota dysbiosis. Although nicotine has been implicated in neuroprotection, whether its enantiomers exert stereoselective effects on the gut-brain axis remains unknown.

Vast offshore habitats face threats including mining, trawling, and drilling for oil

Researchers are preparing to launch an unprecedented trial to protect people exposed to Ebola in the DRC and Uganda