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Fewer outsiders, less feedback, and an uncertain fate for a new science board report

Three research teams have modeled how early embryos find a place to take root

Alzheimer's disease (AD) is traditionally considered irreversible. Here, however, we provide proof of principle for therapeutic reversibility of advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD^(+)) homeostasis, reverses tau phosphorylation, blood-brain barrier deterioration, oxidative stress, DNA damage, and neuroinflammation and enhances hippocampal neurogenesis and synaptic plasticity, resulting in full...

Genetic variations in MS4A4A and MS4A6ATriggering receptor expressed on myeloid cells 2 (TREM2) are linked to the regulation of cerebrospinal-fluid-soluble TREM2 levels and are associated with Alzheimer's disease (AD) risk and progression. By modulating MS4A4A using knockout, overexpression, and degrading antibodies in macrophages, microglia, non-human primates (NHPs), and a mouse model of amyloid pathology, we provide evidence that MS4A4A and MS4A6A are negative regulators of both the...

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Quiescence (reversible cell-cycle arrest) and senescence (irreversible arrest) are challenging to distinguish due to a lack of specific biomarkers, yet both arise simultaneously after chemotherapy. While senescence suppresses tumors by limiting proliferation and recruiting the immune system, quiescent cancer cells evade future therapies and may resume proliferation. Here, we pair time-lapse imaging of cell-cycle dynamics with single-cell RNA sequencing after etoposide treatment to differentiate...

Biomarkers of aging have the potential to transform geroscience clinical trials because of their broad applications in stratifying participants, prioritizing interventions, and monitoring responses to geroprotectors. As longevity biotechnology companies (LBCs) continue to plan and launch innovative clinical trials, standard practices in collecting data and applying biomarkers of aging will allow the field to support parallel and ongoing validation and benchmarking efforts for aging biomarkers....

Polyphenols are emerging as promising candidates for promoting healthy aging and neuroprotection. Here, we investigated the effects of quercetin (Q), luteolin (L), and 3-O-methylquercetin (3OMQ), individually and in combination (FORM), on lifespan, healthspan, and neurobehavioral functions in Caenorhabditis elegans. Wild-type and mutant strains (including daf-2, daf-16, and skn-1) were exposed to the compounds, followed by assessments of longevity, motility, senescence biomarkers (lipofuscin and...

Nicotinamide adenine dinucleotide (NAD) has garnered significant attention in recent years due to its central role in cellular metabolism and its potential as a supplement to promote health and longevity. While numerous human studies indicate that NAD supplementation offers benefits with minimal or no side effects, some studies show no observable advantages. This discrepancy highlights the importance of identifying individuals who are most likely to benefit from NAD-based interventions. One...

Declining rates of male fertility pose a significant clinical challenge, while the mechanisms underlying testicular interstitial function remain incompletely understood. Here, we conducted a comprehensive analysis of the single-cell transcriptomic landscape of the murine testicular interstitium across the postnatal lifespan. The investigation unveiled a previously unrecognized population of Cd34^(+)/Sox4^(+) mesenchymal cells nestled within the interstitium, hinting at their potential as Leydig...

Stem cell-derived extracellular vesicles (EVs) show promise as a therapeutic approach for neurodegenerative diseases, particularly Alzheimer's Disease (AD), where traditional regenerative interventions have achieved limited success. Our previous research demonstrated the neuroprotective benefits of human neural stem cell (hNSC)-derived EVs in 2- and 6-month-old AD mice (5xFAD) that exibited improved cognitive function and reduced AD-related neuropathology. This study aimed to compare the...

Brain capillaries are sensors of neural activity. When a brain region is active, capillary endothelial cells (ECs) sense neuron-derived mediators and elicit a local increase in blood flow (functional hyperemia) to support the rise in metabolic needs. This hyperemic response involves a rapid electrical component and a slower chemical component that involves Gαq PCR (G(q)PCR) activation by agonists released from neurons. The intravascular forces associated with hyperemia engage mechanosensitive...

Histone post-translational modifications (PTMs) are critical regulators of chromatin structure and gene expression, with broad implications for development, metabolism, and aging. While canonical modifications such as methylation and acetylation are well characterized, the role of histone succinylation remains poorly understood. Here, we investigated histone succinylation in the context of aging and exceptional longevity. Using mass spectrometry-based proteomics, we quantified histone...

DNA methylation variation is associated with chronological ageing. Calorie restriction (CR) prolongs lifespan and healthspan in many species. Our hypothesis is that CR has an impact on DNA methylation patterns with increased CR leading to slower epigenetic ageing. We studied the effects of graded CR in male C57BL/6J mice on liver DNA methylation. Mice were fed ad libitum (AL) in the dark-phase or restricted by 10%, 20%, 30% or 40% from 5-months old for 19-months. Livers were collected in...

Osteoporosis is characterized by reduced bone mass and structural deterioration, leading to increased fracture risk, particularly in older adults. Parathyroid hormone (PTH) is a widely used anabolic therapy for osteoporosis; however, rapid bone loss after treatment discontinuation presents a significant clinical challenge. Cellular senescence has been implicated in age-related bone fragility. However, its role in PTH-induced bone remodeling and post-treatment bone loss remains unclear. This...

Cellular senescence, defined as the irreversible arrest of cell proliferation in response to stress, contributes to tissue dysfunction and drives the progression of age-related diseases. Accurate detection of senescent states is therefore essential for understanding aging mechanisms and identifying therapeutic targets. However, conventional laboratory assays are time-consuming and difficult to scale. Here, we present SenSeqNet, a deep learning framework that predicts cellular senescence directly...

Somatic differences in mitochondrial DNA (mtDNA) have been observed with aging and between brain regions for mutations, structural variation, and abundance, which are represented by single nucleotide variants (SNVs), large deletions, and copy number, respectively. We used bioinformatic methods to interrogate mtDNA changes and their relation to cortical and cerebellar aging using whole genome sequencing data from the North American Brain Expression Consortium. This dataset contained 292 unpaired...

CONCLUSION: OOT may potentially contribute to healthy aging by modulating redox adaptability. Its theoretical effectiveness is dose-dependent, with maximal benefit in aged or dysfunctional systems requiring reactivation of flexible stress responses. However, while the model offers insights into possible dynamic behaviours of the redox-inflammatory axis under ozone exposure, it is not yet calibrated to biological data and cannot predict real-world outcomes without further experimental support.