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Optical illusions trick enemies into misjudging the insects’ speed and direction

Google DeepMind team inserts identifiable pattern into protein’s sequence without compromising its structure or function

In Alzheimer's Disease (AD) the default mode network (DMN) exhibits selective vulnerability to functional decline and amyloid beta (Aβ) plaques in early AD. DMN vulnerability may simply be the result of Aβ accumulation. Alternately, Aβ may unmask an intrinsic susceptibility of DMN circuits. Should DMN vulnerability persist amidst global Aβ deposition, this would support the latter hypothesis. We tested this using long-term, multi-region recordings of single units in mice characterized by...

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Alternative polyadenylation (APA) has a central role in regulation of the fate of mRNA and exhibits high variability in the brain and in neurons. However, brain APA regulation has not been mapped at cell type resolution, and the genetic control of APA in brain cell types and its contribution to genetic disease have remained unclear. Here we report a single-cell atlas of APA of the aged human brain across 2 million cells from 379 human postmortem brains across individuals with and without...

Most neurodegenerative diseases are thought to spread through the brain by prion-like mechanisms, in which filamentous protein assemblies self-propagate by templated seeding¹. Distinct conformations of amyloid filaments may provide the physical basis for the strains that lead to different diseases². However, a central pillar of the prion hypothesis, that strains retain their structural identity upon transmission, has not been demonstrated. Here we show that the injection of tau filaments from...

Hutchinson Gilford progeria syndrome (HGPS) is a fatal premature aging disorder caused by pathogenic farnesylated lamin A variants that disrupt nuclear architecture and DNA repair. Current therapies, including farnesyltransferase inhibitors, provide only modest survival benefits and lack molecular specificity, while mutation-specific genome-editing strategies cannot address atypical laminopathies. Here, we develop Farnesylation Amino acid Targeted Editing (FATE), a mutation-agnostic base-editing...

Estrogen Receptor alpha (ERα) is the primary driver in ER+ breast cancer and can be targeted using small molecules such as fulvestrant, a selective estrogen receptor degrader (SERD). Despite being approved over two decades ago and used regularly in post-menopausal women, its precise anti-tumor mechanism remains unclear, with several reports showing efficacy without the requirement for ERα degradation. To investigate the molecular basis of fulvestrant's action, we employed split intein-based µMap...

Ageing has been described through many theoretical frameworks, yet its mechanistic basis remains unresolved. Here we propose that ageing reflects progressive decanalization of mammalian cell identity, driven by erosion of a regulatory grammar written during development. Extending Waddington's epigenetic landscape, development canalizes cell fates through globally coordinated chromatin programs that establish identity constraints across multiple timescales. Subsequently, these constraints can...

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Neurotoxicity is an injury of the central or peripheral nervous system due to harmful stimuli including environmental chemicals, disease-associated endogenous stressors and other exposures that disturb neuronal homeostasis. A common outcome of neurotoxic stress is progressive disruption of synaptic function, redox balance and energy metabolism which together increase vulnerability to regulated cell-death programs. This review focuses on oxidative stress as core driver that shift reactive species...

Epstein-Barr virus (EBV) infects most humans and persists lifelong within a dynamic equilibrium maintained by B-cell latency, cytotoxic T-cell control, NK-cell surveillance and humoral immunity. Ageing can remodel this equilibrium through thymic involution, contraction of the naive T-cell pool, accumulation of late-differentiated or exhaustion-like T-cell states, altered NK-cell function, B-cell dysfunction and chronic low-grade inflammation. Although cytomegalovirus has dominated discussions of...

Misfolded alpha-Synuclein (α-Syn) accumulation is the defining molecular pathology of Parkinson's disease (PD), yet blood-based assays remain challenged by the high background of peripheral α-Syn originating mainly from red blood cells. Neuronal extracellular vesicles (EVs) circulating in blood offer a biologically enriched source of brain-derived α-Syn proteoforms, but their ultralow abundance has hindered reliable detection. Here, we introduce an organic electrochemical transistor-based...

Biological aging clocks offer estimations of aging and dementia, yet scalability is limited. We introduce a large-scale, cross-national speech clock derived from 2928 individuals across five Latin American countries, spanning healthy controls (HCs), mild cognitive impairment (MCI), Alzheimer's disease (AD), and non-language/language-dominant frontotemporal dementia (nldFTD/ldFTD). Multimodal acoustic and linguistic features were trained with supervised models to estimate chronological age,...

Lower socioeconomic position (SEP) is related to poor health, and epigenetic aging represents a potential mechanism of action. We aimed to estimate associations between a novel measure of SEP and epigenetic age in a nationally representative cohort. We used data from NHANES survey waves 1999-2000 and 2001-2002. Our exposure was a novel three-category indicator of SEP, incorporating income, wealth, occupational status, and educational attainment. Our outcomes included 13 different epigenetic...

The mitochondrial prohibitin (PHB) complex is essential for mitochondrial homeostasis, yet its depletion produces opposite effects on lifespan: shortening it in wild-type C. elegans but extending it in insulin/IGF-1 receptor daf-2 mutants, which show an attenuated mitochondrial unfolded protein response (UPR^(mt)). To identify regulators of this differential stress response and its role in aging, we conducted the first genome-wide double-RNAi screen in C. elegans. We identify the...

Patients with chronic traumatic brain injury (cTBI) experience long-term exacerbated neurological decline, which is even more severe in older patients, yet the underlying mechanisms remain unclear. Cranial bone marrow (CBM) has recently been recognized as an adjacent immune surveillance organ of the brain that rapidly responds to acute brain injury. We investigated whether CBM-derived immune cells contribute to chronic neuroinflammation after cTBI by integrating clinical specimens, cell-tracing...

Currently, no generalizable tools exist for predicting the impact of interventions on aging using gene expression changes. Here, we build a model for predicting potential geroprotectors by deconstructing the aging transcriptome into coexpression modules and identifying those modulated by life span-extending interventions in Caenorhabditis elegans (C. elegans). Many of these modules exhibited adaptive changes during aging that are linked to longevity. Using these longevity-associated modules, we...