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Only one workout helped older adults lose fat and keep muscle

15 hours 45 minutes ago
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.

Dystrophic changes of nigrostriatal axons harboring a SYNJ1 Parkinson's mutation suggest catastrophic failure of endocytic mechanisms

16 hours 43 minutes ago
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...
Yumei Wu

A second-generation "hypoxia in a pill" rescues neurodegenerative phenotypes across distinct mouse models

16 hours 43 minutes ago
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...
Hong Wang

A neuronal GPCR modifies neuropeptide signaling to suppress proteostasis in distal tissues

16 hours 43 minutes ago
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...
Joud Hirbawi

A second-generation "hypoxia in a pill" rescues neurodegenerative phenotypes across distinct mouse models

16 hours 43 minutes ago
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...
Hong Wang

Targeting SUV39H2 exon skipping reverses resistance to CDK4/6 inhibitors via transcriptional activation of p21

16 hours 43 minutes ago
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...
Shiyi Yu

Senescent tumor cell membrane-based "time engine" nanosystem amplifies endoplasmic reticulum targeting for metastasis blockade

16 hours 43 minutes ago
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...
Jing Tao

A neuronal GPCR modifies neuropeptide signaling to suppress proteostasis in distal tissues

16 hours 43 minutes ago
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...
Joud Hirbawi

Sex-Specific Neurogenic and Cognitive Responses in a Murine Model of Accelerated Aging

16 hours 43 minutes ago
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...
Ricardo Gómez-Oliva

Birthweight and Breastfeeding Shape Patterns of Biological Aging Across Adult Organs

16 hours 43 minutes ago
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....
Wenming Wei

Sex-Specific Neurogenic and Cognitive Responses in a Murine Model of Accelerated Aging

16 hours 43 minutes ago
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...
Ricardo Gómez-Oliva

When to Trust Epigenetic Clocks: Avoiding False Positives in Aging Interventions

16 hours 43 minutes ago
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...
Daniel S Borrus

Vitamin D Deficiency, Supplementation, and Aging-Related Morbidity and Mortality Across Two Longitudinal Population Cohorts

16 hours 43 minutes ago
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...
Ariel Israel

Bacteria turn a virus’ own weapon against it

16 hours 52 minutes ago
Researchers have uncovered a new way bacteria detect viral attacks: a virus-produced enzyme cuts a bacterial sensor protein, triggering a self-destructing immune response. The discovery could lead to more effective phage therapies against antibiotic-resistant bacteria and provide insight into ancient immune mechanisms shared with humans.