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Alzheimer's disease is triggered by amyloid-β, with symptoms linked to synapse loss. Oligomeric amyloid-β, rather than monomeric or fibrillar amyloid-β, has been proposed to be the proximate mechanistic cause, but the relevant molecular characteristics have remained unclear. To define the biologically relevant species, we isolated a receptor-bound amyloid-β pool from Alzheimer's disease brain by release with a receptor antagonist and purification to homogeneity. This discrete receptor-bound...

Aging is a major contributor to the increasing incidence of acute kidney injury (AKI) and chronic kidney disease (CKD), however the molecular events explaining aging-related nephropathies remains elusive. Here, we found that the RAS signaling adapter protein Erbin (ErbB2-interacting protein) is abundantly expressed in renal tubular cells, but its levels are decreased in murine AKI models and human CKD patient samples. Tubule-specific deletion of Erbin rendered mice highly susceptible to acute...

Healthy aging is associated with structural and functional brain changes. However, cognitive abilities vary in how they change with age: executive functions decline, while aspects of linguistic processing remain relatively preserved. This heterogeneity predicts differences among brain networks in whether and how they change with age. To evaluate this prediction, we used precision fMRI to examine the language-selective network and the Multiple Demand (MD) network, which supports executive...

Food insecurity is increasingly recognised as a public health concern among older adults, yet the mechanisms linking it to mortality remain unclear. Gianfredi and colleagues recently examined this association using data from the English Longitudinal Study of Ageing (ELSA), reporting that food insecurity was associated with a 41% higher risk of all‑cause mortality and a 126% higher risk of premature mortality (before age 75). While the study addresses an important question using a large,...

The pathological hallmarks of neurodegeneration are the aberrant post-translational modification and aggregation of proteins. Genetic factors, like APOE4, increase the prevalence and severity of tau, amyloid, and α-synuclein pathologies. However, the human brain is largely inaccessible during this process, limiting mechanistic understanding. Here, we developed an iPSC-based 3D model that integrates neurons, glia, myelin, and cerebrovascular cells into a human brain-like tissue ("miBrain")....

Pancreatic cancer remains at a stagnant 5-year survival of <13%, attributed to the high heterogeneity and plasticity of these tumors. To circumvent this, we focus on the abundant nuclear protein high mobility group-box protein 2 (HMGB2). HMGB2 depletion is key for establishing replicative senescence in normal cells, but it is significantly overexpressed across multiple cancer types. Here, we combine single-cell and spatial genomics with patient-derived organoids and tumor samples to show how...

Considerable progress in oncology has substantially reduced cancer-related mortality, as reflected by the growing number of cancer survivors. In this context, the management of adverse events associated with cancer treatments has become even more important. Small-molecule VEGFR inhibitors are associated with clinically relevant cardiovascular and hepatic adverse events, including arrhythmias, heart failure, liver enzyme elevations, and hepatic failure. This review integrates the clinical...

Human menopause and the prolonged post-reproductive lifespan (PRLS) are distinctive features of female aging with profound implications for long-term health. Evolutionary theories, such as the Grandmother Hypothesis and other models (e.g., intergenerational reproductive conflict), suggest menopause evolved under ancestral conditions of high extrinsic mortality in early life, short lifespans, and inclusive-fitness benefits derived from kin investment. In such environments, postmenopausal survival...

Cellular senescence is characterized by cell cycle arrest accompanied by mitochondrial dysfunction. Despite extensive efforts to overcome this stable state of growth arrest, effective strategies for treating cellular senescence have not been identified. In this study, we screened plant-derived secondary metabolites and confirmed that formononetin is a substance that potently induces the proliferation of senescent fibroblasts. Formononetin-induced proliferation was associated with the suppression...

Distinct behaviors require the nervous system to execute specialized motor programs, each characterized by unique patterns of body muscle coordination. Whether the execution and adaptation of these programs follow conserved principles across species and perturbations remains unclear. To compare motor programs across species, perturbations, and behaviors, we developed the Python toolbox Automated Gait Analysis (AutoGaitA). Using AutoGaitA and inferring from kinematics, we found that locomotor...

Aging increases tendon injury incidence and poor repair outcomes, but age-related differences in tendon mechanical properties and underlying mechanisms remain unclear. We first analyzed data from the Global Burden of Disease (GBD) database to characterize the associations between aging and population-level changes in tendon injury burden. We found the age-standardized incidence rate (ASIR) of tendon injuries caused by mechanical force decreased with advancing age, whereas the age-standardized...

Epigenetic aging biomarkers are well-established hallmarks of biological aging, yet their metabolic underpinnings remain largely unexplored. Here, we characterized metabolic signatures associated with five epigenetic aging biomarkers (HorvathAge, HannumAge, DNAmPhenoAge, DunedinPACE, and DNAmTL) and examined their clinical relevance and potential determinants in 7162 Chinese older adults from two cohorts (primary and validation). We observed both shared and distinct metabolic associations across...

Gut bacteria can transform nitrate and plant-based iron from vegetables and other foods into protective molecules that may benefit the heart and metabolism. In experimental models, higher levels of these compounds were linked to lower blood pressure, better blood sugar control, healthier blood vessels, and less liver fat.

Researchers have uncovered a possible reason why the Alzheimer’s risk gene APOE4 can disrupt the brain long before memory problems begin. In mice, APOE4 increased a protein called Nell2, shrinking neurons and making memory circuits unusually active. That early hyperactivity predicted worse memory later in life. Reducing Nell2 in adult mice reversed the abnormal changes, raising hopes for a new way to intervene before Alzheimer’s progresses.