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How smallpox reached the Americas: first genomic evidence points to Europeans
The power of ignorance and peering into the Milky Way: Books in brief
Scientists discover how obesity may fuel Alzheimer’s disease
Researchers have uncovered a possible biological pathway connecting obesity to Alzheimer’s disease. Obesity appears to raise levels of certain fat molecules that can travel to the brain, disrupt its immune defenses, and promote harmful amyloid buildup. Correcting this fat imbalance improved memory and brain function in Alzheimer’s models.
Scientists find a simple routine linked to less pain and depression
Keeping a regular daily schedule may help reduce pain and depression, especially among older adults with insomnia. Researchers found that consistent times for waking, eating, socializing, and sleeping were linked to better well-being regardless of sleep quality. These routines may strengthen the body’s internal clock and limit the disruptive effects of “social jet lag.”
Rice bran compound may help ease irritable bowel symptoms
A compound in rice bran may help calm an overactive gut by reducing the calcium signals that cause intestinal muscles to contract. Ferulic acid suppressed contractions triggered by several chemical messengers in laboratory experiments. The discovery could eventually support new dietary approaches for diarrhea-related digestive disorders, although it may make constipation worse.
Depression and amyloid-β across CSF, PET, and plasma biomarkers: a systematic review and meta-analysis
Alzheimer's disease is increasingly defined by biomarker evidence of amyloid-β and tau pathology, sharpening questions about whether late-life depression contributes to, or instead reflects, this pathology. We conducted a systematic review and meta-analysis of studies published between 2000 and 2025 that compared amyloid-β biomarkers in adults with and without depression, with depression defined by validated clinical diagnoses or symptom rating scales. Twenty-four studies were included, spanning...
Agentic AI for scaling diagnosis and care in neurodegenerative disease
US healthcare systems are struggling to meet the growing demand for neurological care, particularly in Alzheimer's disease and related dementias. Generative artificial intelligence (AI) built on large language models now enables agentic AI systems that can streamline clinical workflows, integrate multimodal data and learn from practicing specialists. We envision an agentic AI system that scales specialist-level care to nonspecialist clinical settings through a continuously learning healthcare...
The cross-site reproducibility of MRI morphometric phenotypes in psychiatric disorders
Decades of structural magnetic resonance imaging (MRI) studies have documented alterations of gray matter morphometry in psychiatric disorders, but the field has failed to identify any consensus disease phenotypes. Here we examine whether current approaches will ever converge on such phenotypes by evaluating the consistency of brain-wide maps of gray matter volume and cortical thickness differences obtained for each of 59 study sites of five psychiatric disorders (schizophrenia, schizoaffective...
Best Practice in Home-Based Medical Care for Neurodegenerative Diseases: the Taiwan Model
CONCLUSIONS AND IMPLICATIONS: Taiwan's experience highlights the feasibility and effectiveness of integrated home-centered care for neurodegenerative diseases and offers transferable insights for health care systems facing rapid population aging.
Three-dimensional ultrasound shape analysis reveals distinct structural patterns in muscle aging and sarcopenia
CONCLUSION: Aging and sarcopenia induce distinct and measurable muscle shape alterations. Advanced shape modeling, particularly using INR, showed higher sensitivity. Rectus Femoris emerged as a promising candidate for a shape-based biomarker. Although the metrics presented here should not be interpreted as classification metrics, this study provides a reproducible, open-source framework for muscle shape analysis relevant to aging research.
Beyond the barrier: Physiological determinants of nanoformulation availability in the aging brain
Nanomedicine has revolutionized brain-targeted therapeutics; however, most design paradigms remain centered on overcoming the blood-brain barrier while overlooking the dynamic physiological milieu that governs nanoparticle fate after entry. Emerging evidence reveals that barrier penetration alone is insufficient to ensure efficacy, particularly in the aging brain, where vascular stiffness, impaired interstitial flow, reduced glymphatic clearance, and chronic immune activation reshape...
Protein thiol alterations drive pathologic liquid-liquid phase separation in the aging brain
Cellular homeostasis relies on regulation of processes, including protein post-translational modifications (PTMs) and biomolecular condensation. Aging disrupts the equilibrium of these processes, increasing susceptibility to disease and mortality. Here we used chemoproteomic techniques to generate an atlas of cysteine PTMs in the mouse brain and showed that age-related increases in thiol oxidation promoted the formation of biomolecular condensates. By contrast, protein persulfidation, regulated...
The chemotherapy-induced senescence-associated secretome promotes cell detachment and metastatic dissemination through metabolic reprogramming
Cellular senescence is a consequence of many chemotherapeutics that plays context-dependent roles in cancer. Senescent cells secrete an array of factors collectively known as the senescence-associated secretory phenotype (SASP). Here we show that the cisplatin-induced SASP enhances the detachment of high-grade serous ovarian cancer (HGSOC) cells in vitro and dissemination in vivo. We identify fructose as a metabolic component of the SASP that facilitates cell detachment and show that a...
Author Correction: Sleep chart of biological ageing clocks in middle and late life
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Mistakes matter, age doesn't: task outcome modulates implicit motor adaptation similarly in young and older adults
Despite several age-related processes impacting motor performance, older adults often retain the ability to implicitly adapt to sensory prediction errors. Here, we leverage the fact that implicit adaptation is not attenuated by aging to study the impact of aging on responses to motor errors. In other domains, such as reinforcement learning, aging has been shown to influence how task outcomes or rewards are processed and used to guide subsequent actions, with some studies emphasizing that older...
XYomics: detecting sex-dependent molecular mechanisms in omics data
Understanding sex-dependent differences in disease risk, manifestation, and treatment response is essential for precision medicine. While funding agencies now mandate consideration of Sex as a Biological Variable (SABV), existing bioinformatics tools lack systematic approaches to characterize sex-related molecular mechanisms. Current practices frequently treat sex as a confounding variable, which may obscure important biological differences such as sex-specific alterations, sex-dimorphic changes...
Insufficiency of cohesin regulatory protein PDS5B triggers meiotic failure and aneuploidy in oocytes during advanced maternal aging
Oocytes rely on a cohort of proteins whose sustained expression ensures normal meiotic progression and reproductive competence throughout an animal's reproductive life. Age-related declines in these proteins are a major cause of reduced oocyte quality and female fertility during reproductive aging. Here, we report that the cohesin regulatory protein PDS5B, a dynamically maintained factor in oocytes, declines with age and plays a noncanonical role in the spindle pole formation independent of its...
Guanylate kinase 1 is an enzyme responsible for inosine accumulation in RNA of mammalian cells deficient in inosine triphosphatase
Inosine triphosphate (ITP) is a noncanonical nucleotide. Human cells possess inosine triphosphate pyrophosphatase (ITPA), and ITPA deficiency causes ITP accumulation within cells, leading to the onset of "Developmental and Epileptic Encephalopathy 35." Two potential pathways for ITP biosynthesis have been proposed: i) oxidative deamination of the adenine base in adenosine triphosphate or ii) a two-step phosphorylation reaction of inosine monophosphate (IMP), an intermediate in the de novo...
Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders
Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo during aging. Aged lysosomes in brain, heart, muscle, and white adipose tissue accumulated glycerophosphodiesters and cystine, metabolites that are causally linked to juvenile lysosomal storage disorders, Batten disease, and cystinosis. Levels of these metabolites increased linearly with age,...
Signatures of aging and disease in a single organelle
Changes in lysosomal metabolites are associated with both aging organs and lysosomal storage diseases.