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A minimally invasive treatment called GAE is helping people with chronic knee pain get back to gardening, cycling, and other activities without undergoing knee replacement surgery. Early studies suggest the procedure can provide years of relief by reducing inflammation inside the joint.

A new review suggests that doing more exercise and eating more protein than current minimum recommendations may help people stay stronger, sharper, and more independent as they age. The goal isn't building a beach body—it's extending healthspan and maintaining the ability to fully enjoy life for decades longer.

A clinical trial is exploring whether high doses of vitamin B3 could give patients with glioblastoma a better chance against the aggressive brain cancer. Scientists found that niacin may help revive immune cells that tumors shut down, allowing them to attack cancer more effectively. Early results have been promising, with patients showing significantly better progression-free survival than expected.

Unexpected shift in funds has meant sharp drop in grants this fiscal year

Scientists discovered that Heliconius butterflies have evolved an extraordinary lifespan, living several times longer than closely related species. Even more surprising, some show little sign of physical decline as they age. Their unusual pollen-feeding lifestyle may play a role, but the research suggests deeper evolutionary changes are also helping them stay healthy for longer.

Studying the genetic basis of human phenotypes involves two primary strategies. Model-system experiments generate interpretable gene networks but do not establish relevance to human disease. In contrast, statistical genetics identifies variant- and gene-level associations but cannot test mechanistic models. Here, we bridge these approaches by introducing NERINE, a hierarchical model-based rare variant association test that incorporates gene network topology while remaining robust to network...

Glucagon-like peptide-1 receptor (GLP-1R) activation is widely assumed to regulate the metabolic disorder in Alzheimer's disease (AD). However, direct evidence for this hypothesis is lacking, and currently, there is no oral GLP-1R agonist with effective blood-brain barrier-penetrating ability. Here, we show that a candidate peptide, OHP2, an oral GLP-1R agonist with blood-brain barrier permeability, exhibits promising therapeutic potential for AD. OHP2 primarily activates GLP-1R on astrocytes,...

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Poly-ADP-ribosylation (PARylation), catalyzed by the enzyme PARP1, involves the addition of poly-ADP-ribose polymers (PAR) and has been associated with α-synuclein aggregation in Parkinson's disease (PD) models. This study aimed to unravel the role of PARylation in α-synuclein aggregation and neuronal cell death in the complex environment of post-mortem human PD brains. Using high-resolution imaging and 3D reconstruction analysis, we observed that PAR accumulate in the cytoplasm in regions...

Cells release heterogeneous extracellular vesicles and particles (EVPs) into circulation, carrying RNA and proteins that reflect their origin. Recently, brain-derived EVs have gained significant attention as non-invasive biomarkers for Alzheimer's disease (AD). Here, we identified sub-50nm extracellular nanoparticles in human brain and blood that lack the hallmarks of small EVs, exosomes, exomeres, and supermeres but are enriched for brain-specific markers, hereafter termed small EPs or...

Trained immunity, an emerging treatment strategy, confers long-term anti-tumour memory by modulating epigenetic and metabolic reprogramming of innate immune cells, offering a novel pathway for immunotherapy of haematological malignancies. This article systematically outlines the mechanisms by which inducers such as β-glucan, Bacille Calmette-Guérin (BCG) and cytokines train key effector cells including macrophages and natural killer (NK) cells. It further analyses how ageing-encompassing both...

The human antiviral antibody reactome provides a cumulative molecular record of immune exposures. Using high-resolution VirScan profiling, we compared epitope-level antibody responses across early childhood and adulthood. Infants are born with maternal IgG antibodies, but these antibodies decay rapidly and are replaced by endogenous responses to ~22 new viral exposures within three years. Pediatric antibody reactivities remain highly dynamic until about age 7 and are broad in epitope specificity...

Nutrition shapes development, health and risk of disease over the life course and across generations. The predominant approaches to understanding these relationships have either been to consider the effects of single nutrients, one at a time, or to consider associations with food types and dietary patterns. Although, to date, the single-nutrient approach has defined much of the scientific enquiry and public debate on the macronutrients - carbohydrate, fat and protein - there is an emerging...

Biodiversity loss in the present era requires new tools for studying nonmodel organisms. Elephants are both an endangered species and excellent models for studying complex phenotypes including size, social behavior and longevity. Here we report the first derivation of elephant (Elephas maximus) induced pluripotent stem (emiPS) cells. We achieved emiPS cells using two approaches: (1) a two-step process of chemical media induction and colony selection followed by over-expression of elephant...

Incidence of early-onset cancer is rising globally in recent generations, which underscores the need to elucidate the influence of emerging generational risk factors. Systemic and organ-specific aging reflects the cumulative impact of exposures and may provide an integrative and complementary approach to understand early-onset cancer risk. Here among 154,169 young adults from the United Kingdom Biobank, systemic aging measured by PhenoAge increased across birth cohorts, with 23% s.d. increase...

Hepatic inflammation and immunosurveillance play major roles in the progression of liver cancer. A common trigger for hepatic inflammation is oxidative stress, which stems from mitochondrial dysfunction. Here, we demonstrate that deletion of the mitochondrial stress integrator OMA1 increases hepatic primary tumor incidence and impairs survival in mice. Persistent activation of the KEAP1-Nrf2 oxidative stress pathway in the absence of OMA1 promotes early liver injury, which progresses into...

Amyloid-β 1-42 (Aβ42) aggregation is among the earliest pathological signs in Alzheimer's disease (AD). Here, we characterized Aβ42 species at several aggregation stages at the single-molecule level and examined their toxicity in murine organotypic brain slices, where we observed a stage-dependent recapitulation of multiple aspects of the cellular phase of AD. Aggregates formed during the lag phase of the Aβ42 aggregation elevated neuronal baseline Ca^(2+) levels and impaired long-term...

APOE4, the major genetic risk factor for Alzheimer's disease (AD), and ATP-binding cassette-A1 (ABCA1), required for lipidation of APOE are gene products of the liver X receptor (LXR) receptor. LXR agonists have been validated in animal models as therapeutics for AD, atherosclerosis, and many other diseases. Clinical progress has been thwarted by unwanted hepatic lipogenesis. Structurally diverse LXR ligands were profiled in coregulator TR-FRET (CRT) assays analyzing ligand-induced coactivator...

The accumulation of aberrant proteins or their impaired clearance leads to neurodegenerative diseases (NDs). The protein amino terminus (Nt) and its modifications determine the fate of proteins and their cellular effects. Nt acetylation, Nt methylation, and Nt myristoylation are protein Nt modifications implicated in the pathogenesis of proteinopathies like Alzheimer's, Parkinson's, and Huntington's diseases by regulating the protein lifespan, folding, and interaction with protein/DNA. In...

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) represent a promising cell-free strategy for intervertebral disc degeneration (IDD). Here, we obtained oxidative stress-preconditioned exosomes (O-Exos) from BMSCs exposed to low-concentration hydrogen peroxide. Compared with exosomes from untreated cells (N-Exos), O-Exos more effectively delayed nucleus pulposus (NP) cell senescence and attenuated IDD in vitro and in vivo. The superior effects of O-Exos were associated with...