Aggregator

Failed supernova candidate points to a stealthy pathway of stellar collapse

Dredging and mining sediments increases flood risks and threatens infrastructure, researchers say

Microglia display remarkable plasticity, with their cellular states evolving in response to developmental stage, regional context, and environmental or pathological stimuli. In this issue of Immunity, Hamagami et al. demonstrate that adaptive reconfiguration of regulatory networks, particularly the dynamics of enhancers, underlies these state transitions. Conserved enhancers link developmental and Alzheimer's-related microglial states, suggesting shared epigenetic frameworks that influence...

Counteracting cognitive decline is a declared goal of regenerative medicine. Recently, partial cellular reprogramming has emerged as a promising strategy to promote tissue regeneration and restore cellular function, but whether this approach bears fruit when targeted to cell populations underlying cognitive processes remains unknown. Here, we report that partial reprogramming of engram neurons-bona fide memory trace cells-by OSK-mediated gene therapy reversed the expression of senescence- and...

No abstract

No abstract

This study conducted exploratory analyses of the effects of BIIB080, a MAPT (microtubule-associated protein tau)-targeting antisense oligonucleotide, in participants with mild Alzheimer's disease. A multicenter, randomized, double-blind, phase 1b trial was conducted as a placebo-controlled, multiple-ascending dose (MAD) study followed by an open-label, long-term extension (LTE). During the MAD study, participants were randomized and received either intrathecal placebo or BIIB080 10 mg (n = 6),...

Immunotherapeutic approaches to brain aging remain largely preclinical and in early translational stages, and they have focused mostly on modulating innate immunity. In this issue of Immunity, Negredo et al. identify T cells bearing exhaustion-like signatures as a hallmark of brain aging and reveal the beneficial effects of an engineered IL-10 variant that functionally uncouples pro- and anti-inflammatory signaling in microglia.

Counteracting cognitive decline is a declared goal of regenerative medicine. Recently, partial cellular reprogramming has emerged as a promising strategy to promote tissue regeneration and restore cellular function, but whether this approach bears fruit when targeted to cell populations underlying cognitive processes remains unknown. Here, we report that partial reprogramming of engram neurons-bona fide memory trace cells-by OSK-mediated gene therapy reversed the expression of senescence- and...

Posttraumatic stress disorder (PTSD) is associated with accelerated biological aging. In general, psychological resilience is related to more normative aging patterns; however, among individuals with PTSD, resilience may be associated with older biological aging. For example, prior work suggests that individuals with PTSD who have higher psychological resilience show more advanced epigenetic aging than individuals with lower psychological resilience. We investigated whether psychological...

BACKGROUND: Mobility loss in older adults reduces quality of life and increases risks of falls, hospitalizations, and mortality. Low-functioning (LF) older adults experience faster mobility decline than their high-functioning (HF) peers, but the underlying biological mechanisms remain unclear. Although iron accumulation in aging muscle mitochondria has recently been linked to lower physical function, its longitudinal impact on physical function remains understudied.

CONCLUSIONS: This study depicts the metabolic features of MASLD in the older population. Our finding explores promising biomarkers for diagnosis and provides more perspectives on molecular mechanisms and potential targets for MASLD in the context of aging.

Sleep is viewed typically through a brain-centric lens, with little known about the role of the periphery^(1,2). Here we identify a sleep function for peripheral macrophage-like cells (haemocytes) in the Drosophila circulation, showing that haemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in haemocytes, we discovered that knockdown of eater-a member of the Nimrod...

Nucleotide excision repair (NER) removes bulky adducts from genomic DNA and prevents the ultraviolet light-sensitivity disease xeroderma pigmentosum, cancer and premature ageing¹. After initial lesion recognition by XPC in global genome repair or by stalled RNA polymerases in transcription-coupled repair, a lesion and surrounding DNA duplex are unwound by TFIIH, which includes the ATPases XPB and XPD, and additional NER factors XPA, XPF, XPG and RPA, to form a DNA bubble² comprising around 27...

Ageing has traditionally been interpreted through declining selection gradients with age. The Evolvable Soma Theory of Ageing (ESTA) provides a complementary perspective by proposing that age-associated somatic changes reflect the late extension of the developmental program, which is shaped by evolution. These late-acting changes are epigenetic in nature, encoded in the genome, subject to germline-mediated modification, and may be viewed as developmentally regulated variants that have not yet...

No abstract

Amyloid-β (Aβ) peptides are a defining feature of Alzheimer's disease (AD). These peptides are produced by the proteolytic processing of the amyloid precursor protein (APP), which can occur through the synaptic vesicle (SV) cycle. However, how amyloidogenic APP processing alters SV composition and presynaptic function is poorly understood. Using App knock-in mouse models of amyloid pathology, we found that proteins with impaired degradation accumulate at presynaptic sites together with Aβ(42) in...

The genetic mechanisms of ~90% of Alzheimer's disease (AD)-associated variants residing in noncoding DNA remain poorly understood. To address this, we developed a deep learning framework that integrates bulk histone modification data with single-cell open chromatin profiles to evaluate the regulatory potential of noncoding variants. This model identified 1457 silencer and 3084 enhancer AD-associated variants in dorsolateral prefrontal cortex, classifying gene loci as silencer-only (SL),...

Parkinson's disease (PD) is characterized by α-synuclein accumulation and dopaminergic neuron degeneration, with dopamine (DA) oxidation emerging as a key pathological driver. However, the mechanisms underlying this neurotoxic process remain unclear. Using PD patient-derived and CRISPR-engineered induced pluripotent stem cell midbrain dopaminergic neurons lacking DJ-1, we identified defective sequestration of cytosolic DA into synaptic vesicles, which culminated in DA oxidation and α-synuclein...

“Groundbreaking” study uncovers why adenovirus-based shots caused life-threatening blood clots and bleeding in some people