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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.

Researchers have found a way to slash the processing time for 3D-printed zirconia crowns from as much as 100 hours to under 30 minutes. The advance could eventually let dentists print strong, customized permanent crowns for patients within a single appointment.

Researchers have used AI to uncover the DNA signature of a key genetic “switch” involved in turning genes on. After analyzing about 500,000 DNA sequences, the model identified the initiator in roughly 60% of human genes. The breakthrough could help predict the effects of harmful mutations and eventually contribute to decoding the broader genetic instructions that control gene activity throughout the body.

A decades-old compound may point to a new way of treating obesity by making the body burn more energy rather than simply reducing appetite. In mice, TOFA increased energy use by as much as 18%, reduced body fat without significant muscle loss, and improved blood sugar, triglycerides, and fatty liver disease. It also produced stronger results when combined with GLP-1 drugs such as Ozempic, Wegovy, Mounjaro, and Zepbound.

A massive analysis involving more than 100 million people has found strong links between recreational drug use and stroke, including among younger adults. Cocaine was associated with nearly double the risk of stroke, amphetamines with more than double the risk, and cannabis with a 37% increase.

Older adults with mild cognitive impairment and sleep problems who took at least 5,000 IU of vitamin D daily scored more than 13% higher on a cognitive test than those taking none. The preliminary findings suggest vitamin D could be worth studying as a potentially modifiable factor during an early window of cognitive decline.