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New laser heat treatment could stop blindness before it starts

2 weeks ago
A new experimental treatment could finally offer hope for millions of people with dry age-related macular degeneration — one of the leading causes of blindness in older adults. Researchers at Aalto University discovered a way to gently heat tissue at the back of the eye using near-infrared light, triggering the cells’ natural “cleanup and repair” systems before major damage occurs.

State-specific inhibition of NMDA receptors by memantine provides insight into NMDAR channel blocker tolerability

2 weeks ago
N-methyl-d-aspartate (NMDA) receptors (NMDARs) are key mediators of calcium ion (Ca^(2+)) influx required for proper neuronal function. Excessive NMDAR-mediated Ca^(2+) influx is neurotoxic and associated with neurological disease. Memantine and ketamine, two NMDAR antagonists with overlapping binding sites in the NMDAR channel, are of high clinical interest. Whereas memantine is a well-tolerated Alzheimer's disease medication, ketamine is a fast-acting antidepressant with abuse potential and...
Matthew B Phillips

The PET tracer [<sup>11</sup>C]MODAG-005 targets alpha-synuclein aggregates in the brain

2 weeks ago
Synucleinopathies are neurodegenerative diseases characterized by the presence of brain inclusions containing the pathologically aggregated protein α-synuclein. The development of a positron emission tomography tracer to detect aggregates of misfolded α-synuclein could revolutionize early diagnosis, disease monitoring, and the evaluation of therapeutic efficacy. Here, we present the development, preclinical validation, and first-in-human evaluation of [^(11)C]MODAG-005. In vitro binding...
Ran Sing Saw

Lifespan normative modeling of brain microstructure

2 weeks ago
Normative models of brain metrics based on large populations could be extremely valuable for detecting brain abnormalities in patients with a variety of disorders, including degenerative, psychiatric and neurodevelopmental conditions, but no such models exist for the brain's white matter (WM) microstructure. Here we present a large-scale normative model of brain WM microstructure - based on 19 international diffusion MRI datasets covering almost the entire lifespan (totaling N = 54,583...
Julio E Villalón-Reina

Brain maintenance biomarkers from structural and functional interactions in aging and neurodegeneration

2 weeks ago
Brain maintenance may help explain why some individuals remain cognitively resilient despite aging, but its biological basis is not well understood. Here, we show that brain maintenance can be quantified from the relationship between brain structure and function. Using structural MRI and resting-state functional MRI from 1280 older adults, we built a model based on young adults to estimate the functional capacity supported by preserved brain structure, and defined brain maintenance as the...
Yumeng Li

Universal transcriptomic hallmarks of mammalian ageing and mortality

2 weeks ago
Ageing and interventions modulate health and mortality¹, yet the underlying molecular mechanisms of this modulation remain unclear. Here we integrate more than 11,000 transcriptomes from more than 25 tissues across 4 mammals (mouse, rat, macaque and human) to develop accurate, interpretable rodent and multi-species biomarkers of chronological age and expected mortality, predicting lifespan-modulating interventions, time to death, chronic diseases and rejuvenation. Ageing-related changes were...
Alexander Tyshkovskiy

Mechanism of age-related accumulation of mtDNA mutations in human blood

2 weeks ago
Accumulation of mutant mitochondrial DNA (mtDNA) heteroplasmy is among the strongest signatures of ageing¹. Here we investigated the underlying mechanism by calling mtDNA sequence, mtDNA abundance and mtDNA heteroplasmic variants in human blood using whole-genome sequences from approximately 750,000 individuals. We observed that mtDNA single-nucleotide variants (mtSNVs) accumulate sharply at age 60 years, occur at low levels of heteroplasmy, exhibit little evidence of positive selection and are...
Rahul Gupta

Human haematopoietic stem cells remember inflammatory stress

2 weeks ago
Inflammation activates blood cells, contributing to ageing and malignancy^(1-3). Haematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long haematopoiesis^(1-9), but how human HSCs respond and adapt to inflammatory stress is largely unknown. Here, to empirically understand this adaptation, we developed xenograft inflammation-recovery models and performed single-cell multiomics on xenografted human HSCs. Two transcriptionally and epigenetically distinct HSC subsets were...
Andy G X Zeng

Lifespan normative modeling of brain microstructure

2 weeks ago
Normative models of brain metrics based on large populations could be extremely valuable for detecting brain abnormalities in patients with a variety of disorders, including degenerative, psychiatric and neurodevelopmental conditions, but no such models exist for the brain's white matter (WM) microstructure. Here we present a large-scale normative model of brain WM microstructure - based on 19 international diffusion MRI datasets covering almost the entire lifespan (totaling N = 54,583...
Julio E Villalón-Reina

Glycogen drives the sensory activation of POMC neurons

2 weeks ago
Hypothalamic POMC neurons modulate systemic energy balance and glucose homeostasis by sensing nutritional state signals. In addition to this classic regulatory mode, these neurons are also activated by the sensory perception of food. Here, we report that food-related sensory cues engage glycogen metabolism in POMC neurons. Genetic depletion of glycogen through various approaches renders POMC neurons unresponsive to food-associated sensory stimuli. This defective perception of food is linked to...
Alicia G Gómez-Valadés

Multicellular senescence impairs skeletal muscle recovery following disuse in aging

2 weeks ago
Aged skeletal muscle has a diminished capacity to recover after disuse. Although muscle regrowth requires coordinated interactions between immune and progenitor cells, the mechanisms of impaired remodeling in aged skeletal muscle remain poorly understood yet possibly involve the accumulation of senescent cells. We used a flow cytometry approach coupled with scRNAseq to determine the muscle senescent cell identity and transcriptional landscape during skeletal muscle recovery following disuse...
Paul-Emile Bourrant

TPM1 drives cytoskeleton-immunometabolism coupling and LGALS9/CD45-mediated neuroinflammatory propagation in retinitis pigmentosa

2 weeks ago
Retinitis pigmentosa (RP), the most prevalent inherited retinal degeneration, features progressive photoreceptor loss with no approved disease-modifying therapies. While microglia-driven neuroinflammation accelerates RP progression, its sustaining mechanisms remain elusive. Through integrated multiomics profiling of retinal degeneration 10 (rd10) mice, we identify tropomyosin 1 (TPM1) as a previously unrecognized cytoskeletal-immune regulator orchestrating spatial neuroinflammation in RP....
Rong Li

Natural tissue immortality: Indefinite survival of sea cucumber explants

2 weeks ago
Senescence and immortality are central biological paradigms. While regenerative capabilities in Deuterostomia are known, the fate of lost and discarded tissues has been presumed terminal. Here, we demonstrate that explanted epidermal, connective, neural, and muscle tissue from the sea cucumber Psolus fabricii (Holothuroidea: Echinodermata) healed and continued to grow in natural, nonaxenic seawater without supplementation for more than 3 years. In experimental trials, these explants, termed...
Sara Jobson