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Bizarre discovery of interspecies cloning “almost impossible to believe,” biologists say

Studies identify a solid inner core and buried remnants of giant impacts

Neuroinflammation drives Alzheimer's disease (AD) pathogenesis. Z-DNA, a non-canonical left-handed DNA structure, activates innate immune signaling through Z-DNA-binding protein 1 (ZBP1). However, the functional significance of ZBP1-mediated Z-DNA detection in AD remains undefined. Here, we found that ZBP1 is amplified in AD microglia, driving innate immune responses and neuroinflammation through sensing Z-form mitochondrial DNA (mtDNA). We show that oxidized mtDNA, generated by amyloid-β...

Alzheimer's disease (AD), a progressive neurodegenerative disorder, poses significant therapeutic challenges due to its complex etiology and limited treatment options. Traditional pharmacotherapies targeting amyloid-β (Aβ) and cholinergic pathways offer modest benefits and are often associated with adverse effects. Emerging evidence implicates gut dysbiosis and the gut-brain axis in the pathogenesis and progression of AD. This review explores the multifactorial pathophysiology of AD and...

Deep brain stimulation (DBS) substantially improves motor symptoms and quality of life in people with movement disorders such as Parkinson disease and dystonia, and it is also being explored as a treatment option for other brain disorders, including treatment-resistant obsessive-compulsive disorder, Alzheimer disease and depression. Two major developments are currently driving progress in DBS research: first, the framework of adaptive DBS, which senses brain activity to infer the momentary state...

Phospho-tau protein p-tau181 is a cerebrospinal fluid biomarker for Alzheimer's disease (AD), while p-tau217 is the most sensitive plasma biomarker for cerebral amyloid β (Aβ) load prior to tau pathology in preclinical AD. Diagnostic and prognostic use of these p-tau biomarkers requires neuropathological interpretation. Here, we analyzed the cellular localization of biomarker p-tau species in postmortem human brains harboring different extents of Aβ plaque and tau pathology. Signals for p-tau217...

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and aggregation of α-Synuclein (α-Syn). While both genetic and environmental factors are implicated in PD pathogenesis, the mechanisms underlying neurodegeneration induced by environmental toxins and associated genetic responses remain largely unknown. Recently, triggering receptor expressed on myeloid cells 2 (TREM2) has been proven to be a critical mediator of toxin-induced motor...

Despite genome-wide association studies (GWAS) of late-onset Alzheimer's disease (LOAD) having identified many genetic risk loci^(1-3), the underlying disease mechanisms remain largely unclear. Determining causal disease variants and their LOAD-relevant cellular phenotypes has been a challenge. Here, using our approach for identifying functional GWAS risk variants showing allele-specific open chromatin, we systematically identified putative causal LOAD-risk variants in human induced pluripotent...

Several strategies have emerged lately in response to the rapid increase in the aging population to enhance health and life span and manage aging challenges. Developing such strategies is imperative and requires an assessment of biological aging. Several aging clocks have recently been developed to measure biological aging and to assess the efficacy of longevity interventions. Biological age better reflects a person's actual age and is closely associated with health outcomes and time to...

In a multicellular organism, cell lineages share a common evolutionary history. Knowing this history can facilitate the study of development, aging, and cancer. Cell lineage trees represent the evolutionary history of cells sampled from an organism. Recent developments in single-cell sequencing have greatly facilitated the inference of cell lineage trees. However, single-cell data are sparse and noisy, and the size of single-cell data is increasing rapidly. Accurate inference of cell lineage...

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Over time, cells in the brain and in the body accumulate damage, which contributes to the ageing process¹. In the human brain, the prefrontal cortex undergoes age-related changes that can affect cognitive functioning later in life². Here, using single-nucleus RNA sequencing (snRNA-seq), single-cell whole-genome sequencing (scWGS) and spatial transcriptomics, we identify gene-expression and genomic changes in the human prefrontal cortex across lifespan, from infancy to centenarian. snRNA-seq...

Late-life depression (LLD) arises from the confluence of neurochemical dysfunction, oxidative stress, and neural network disintegration, presenting a formidable therapeutic challenge. Here, we demonstrated that combined vitamin D (Vit D) and L-theanine (L-thea) administration exerts multimodal neurorestorative effects in an aged murine model of unpredictable chronic mild stress (UCMS), addressing the core triad of LLD pathology: dopaminergic decline, redox imbalance, and thalamocortical...

We aimed to assess the validity of predicted repetitions in reserve (RIR) during resistance exercise (RE) in community-dwelling older adults (n = 25; 68 ± 4 yrs.; body mass index [BMI] = 28.1 ± 4.6 kg·m^(-2)). Prior to data collection, participants were familiarized with resistance training as well as with the use of RIR and rating of perceived exertion (RPE). Participants completed a one-repetition maximum (1RM) test in the chest press exercise. The repetitions-to-failure test, used to...

Differential expression analysis is crucial in genomics, yet most methods focus only on mean shifts. Variance shifts in gene expression-especially in cellular signaling and aging-are increasingly recognized as being biologically important. We present QRscore (quantile rank score), a general non-parametric framework that extends the Mann-Whitney test to detect both mean and variance shifts through model-informed weights derived from negative binomial (NB) and zero-inflated NB (ZINB)...

Nuclease-helicase DNA2 is a multifunctional genome caretaker that is essential for cell proliferation in a range of organisms, from yeast to human^(1-4). Bi-allelic DNA2 mutations that reduce DNA2 concentrations cause a spectrum of primordial dwarfism disorders, including Seckel and Rothmund-Thomson-related syndromes^(5-7). By contrast, cancer cells frequently express high concentrations of DNA2 (refs. ^(8-11)). The mechanism that precludes cell proliferation in the absence of DNA2 and the...

Aging is a major risk factor for neurodegenerative diseases associated with protein aggregation, including Huntington's disease and amyotrophic lateral sclerosis (ALS). Although these diseases involve different aggregation-prone proteins, their common late onset suggests a link to converging changes resulting from aging. In this study, we found that age-associated hyperactivation of EPS8/RAC signaling in Caenorhabditis elegans promotes the pathological aggregation of Huntington's disease-related...

While research suggests that playing musical instruments promotes neuroplasticity in professional musicians, it remains unclear whether lifelong music experience benefits brain health in non-professional musicians. This study examined whether playing a musical instrument across the lifespan is associated with (a) altered grey matter (GM) density and (b) neuropsychological functioning in older adults at risk for dementia. Sixty-one individuals aged ≥ 50 years were recruited from a memory clinic....

CONCLUSION: Worse global cognitive function and greater WMHs may collectively increase the risk of suicidal attempts in LLD patients.