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Teams led by physicist used “BootLoops” software to produce 36 papers in weeks on everything from linguistics to health policy

A six-month study suggests that high-intensity interval training (HIIT) may offer older adults a powerful advantage: losing body fat while keeping their muscle. Unlike moderate-intensity workouts, which led to a small loss of lean muscle, HIIT preserved it while also improving body composition around the waist.

Parkinson's disease (PD) is a systemic disorder linked to gut dysbiosis, yet key microbiota-regulated metabolites remain unclear. Here, we observe elevated taurochenodeoxycholic acid (TCDCA) in patients with PD that correlates with disease severity. Reduced bile salt hydrolase (BSH) gene abundance correlates inversely with circulating TCDCA, consistent with altered bile acid deconjugation. Exogenous TCDCA correlates with aggravated motor and gastrointestinal deficits, impaired blood-brain...

Tau phosphorylation is classically associated with neurodegeneration, yet similar phosphorylation patterns emerge during physiological states and acute stress responses. How these overlapping patterns of phosphorylated Tau (pTau) relate to neuronal adaptation and Alzheimer's disease pathology remains unresolved. We synthesize findings from human to rodent and fly brains and from neuronal cell models, across neurodevelopment, sleep, hibernation, cellular stress, and disease. Across these...

Alzheimer's disease (AD) presents distinct extracellular, intracellular and vascular delivery targets, yet brain exposure of candidate therapeutics remains difficult to establish. This narrative review compares hyaluronic acid, chitosan, cyclodextrin, dextran, alginate and pectin systems by construct architecture, route, blood-brain barrier (BBB) evidence, cargo release and biological response. The literature includes covalent drug conjugates, loaded or coated carriers, host-guest complexes and...

Human immune aging is heterogeneous, with immune responses becoming increasingly variable over the lifespan. Here, we integrated seven large-scale public single-cell peripheral blood mononuclear cell (PBMC) datasets and a newly generated cohort, encompassing 2,609 ostensibly healthy individuals across diverse ages, ancestries, and biological sexes. We identified both conserved and cohort-associated age-associated remodeling across 59 immune populations, together with sex- and ancestry-dependent...

Tau phosphorylation is classically associated with neurodegeneration, yet similar phosphorylation patterns emerge during physiological states and acute stress responses. How these overlapping patterns of phosphorylated Tau (pTau) relate to neuronal adaptation and Alzheimer's disease pathology remains unresolved. We synthesize findings from human to rodent and fly brains and from neuronal cell models, across neurodevelopment, sleep, hibernation, cellular stress, and disease. Across these...

Synaptojanin 1 is a brain enriched phosphoinositide phosphatase implicated in endocytosis at the synapse. A mutation (R258Q) that selectively impairs its Sac1 phosphatase domain causes early onset familial Parkinsonism. Neurons of mice with this mutation display synaptic vesicle traffic defects across the brain, but selective dystrophic changes in a subset of dopaminergic axons in the dorsolateral striatum. Using correlative light microscopy-FIB-SEM of mutant mouse striata to visualize in 3D...

A growing body of preclinical research is demonstrating the therapeutic potential of chronic, continuous hypoxia (11% FIO(2)) for rare and common diseases. However, the chronic delivery of hypoxic gas poses both practical challenges and long-term safety concerns. We previously introduced a small-molecule, "hypoxia-in-a-pill" combining a hemoglobin affinity enhancer (GBT440) to limit oxygen delivery with a HIF-2α inhibitor (PT2399) to prevent detrimental compensatory erythropoiesis. Although this...

The proteostasis network (PN) safeguards the integrity of proteins by promoting various cellular activities. However, with aging, the PN's competence declines and aggregated proteins accrue within cells. This process underlies the development of neurodegenerative disorders such as Alzheimer's and Huntington's diseases. While the PN functions within cells, proteostasis is regulated across the organism by intertissue communication, which is partially governed by neurons. We previously found that...

A growing body of preclinical research is demonstrating the therapeutic potential of chronic, continuous hypoxia (11% FIO(2)) for rare and common diseases. However, the chronic delivery of hypoxic gas poses both practical challenges and long-term safety concerns. We previously introduced a small-molecule, "hypoxia-in-a-pill" combining a hemoglobin affinity enhancer (GBT440) to limit oxygen delivery with a HIF-2α inhibitor (PT2399) to prevent detrimental compensatory erythropoiesis. Although this...

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are standard therapies for estrogen receptor-positive breast cancer, but their efficacy is limited by drug resistance. While dysregulation of alternative splicing has been implicated in cancer progression, the underlying mechanisms remain unclear. Here, we uncover a splicing-mediated mechanism whereby exon 2 inclusion in SUV39H2 drives its overexpression in CDK4/6i-resistant breast cancer cells. Clinically, elevated exon 2 inclusion in SUV39H2...

As an important component of biomimetic drug delivery systems, cell membrane-coated nanoparticles are widely used for subcellular delivery. However, the influence of cell membranes at different life cycles on subcellular delivery remains unexplored. Our previous study demonstrated that senescent tumor cell membrane-coated nanoparticles (SNP) displayed superior endoplasmic reticulum (ER) targeting efficiency in tumor cells. After inducing tumor cells into senescence, SNP showed greater...

The proteostasis network (PN) safeguards the integrity of proteins by promoting various cellular activities. However, with aging, the PN's competence declines and aggregated proteins accrue within cells. This process underlies the development of neurodegenerative disorders such as Alzheimer's and Huntington's diseases. While the PN functions within cells, proteostasis is regulated across the organism by intertissue communication, which is partially governed by neurons. We previously found that...

Aging is associated with cognitive deterioration accompanied by a reduction in hippocampal neurogenesis. Murine models have been widely used to study aging and age-related cognitive decline, as they recapitulate many of the key features of the degenerative process. Among these, the SAMP8 strain represents a well-established model of accelerated aging, characterized by early-onset and progressive cognitive impairment, Alzheimer's disease-like neuropathology, and an initial increase in hippocampal...

Early-life nutrition may influence long-term health, but its impact on organ-specific biological aging is unclear. We investigated associations of birthweight and breastfeeding with multi-organ aging and potential mediating pathways in adulthood. Using UK Biobank data, we examined associations of retrospectively reported birthweight (n = 21,446) and breastfeeding history (n = 29,713) with 19 proteomics-derived aging indices, comprising 18 organ-specific indices and one composite index....

CONCLUSION: Opioid use is associated with significantly poorer HrQoL in community-dwelling older adults, highlighting the importance of routinely assessing quality of life, functional status, and psychosocial factors among persons who use opioids.

Aging is associated with cognitive deterioration accompanied by a reduction in hippocampal neurogenesis. Murine models have been widely used to study aging and age-related cognitive decline, as they recapitulate many of the key features of the degenerative process. Among these, the SAMP8 strain represents a well-established model of accelerated aging, characterized by early-onset and progressive cognitive impairment, Alzheimer's disease-like neuropathology, and an initial increase in hippocampal...

Epigenetic clocks have emerged as potential biomarkers of aging due to their association with morbidity and mortality. They have recently gained traction as outcome measurements for anti-aging interventions. However, as the number of new epigenetic clocks continues to grow, different clocks may not agree on the effect of an intervention. This raises the question of when researchers can trust epigenetic clock results. In this study, we find that when extending previously published single-clock...

Vitamin D deficiency has been implicated in biological processes linked to aging and organismal resilience, yet its relationship to long-term systemic aging trajectories remains incompletely characterized. We analyzed longitudinal electronic health record data from two large healthcare systems: Leumit Health Services (LHS), a nationwide Israeli health organization, and TriNetX, a federated US research network. We examined more than 1.67 million serum 25-hydroxyvitamin D [25(OH)D] measurements...