Aggregator

Science, Volume 388, Issue 6751, Page 1032-1032, June 2025.

Science, Volume 388, Issue 6751, Page 1031-1031, June 2025.

Science, Volume 388, Issue 6752, Page 1115-1115, June 2025.

Scientists are figuring out where “downscaled” climate models struggle—and how they can be improved

Despite poor conditions, Indigenous growers used innovative techniques to grow large crops of corn, beans, and squash

Continent faces a shortage of doses and distribution challenges

CONCLUSIONS: The study showed an association between quantitatively assessed visual and physical functions in community-dwelling older adults living in Japan. Thus, the findings indicate that maintaining and enhancing grip strength and visual function in older adults may be an important factor in leading a healthy and fulfilling life.

No abstract

Defining how amyloid-β and pTau together lead to neurodegeneration is fundamental to understanding Alzheimer's disease (AD). We used imaging mass cytometry to identify neocortical neuronal subtypes lost with AD in post-mortem brain middle temporal gyri from non-diseased and AD donors. Here we showed that L5,6 RORB^(+)FOXP2^(+) and L3,5,6 GAD1^(+)FOXP2^(+) neurons, which accumulate amyloid-β intracellularly from early Braak stages, are selectively vulnerable to degeneration in AD, while L3...

Mitophagy, the selective autophagic elimination of mitochondria, is essential for maintaining mitochondrial quality and cell homeostasis. Impairment of mitophagy flux, a process involving multiple sequential intermediates, is implicated in the onset of numerous neurodegenerative diseases. Screening mitophagy inducers, particularly understanding their impact on mitophagic intermediates, is crucial for neurodegenerative disease treatment. However, existing techniques do not allow simultaneous...

No abstract

Simultaneously monitoring glutamate (Glu) dynamic at edge of synaptic cleft and peri-soma is crucial for understanding Glu-related pathology. Here, we created an electrochemical Glu sensors toolkit with spatial resolution of ∼60 nm, combining biologically engineered Glu binding protein for specifically capturing Glu together with chemically designed ferrocene groups for signal labeling. Modulation conjugation approach between GluR and ferrocene significantly improved sensitivity up to 32-folds....

No abstract

Gene editing (GE) using homology-directed repair (HDR) in hematopoietic stem and progenitor cells (HSPCs) offers promise for long-range gene correction of inherited genetic disorders. However, cellular responses induced by CRISPR-Cas9/AAV6 engineering impair the long-term repopulating potential of HDR-edited HSPCs, adversely impacting the safety and efficacy of clinical translation. Our study uncovers a durable senescence-like response in genetically engineered HSPCs triggered by p53 and...

CONCLUSION: There was a downward trend in global ICH incidence from 1992 to 2021. Economically developed countries must remain vigilant against the rise in ICH cases due to aging. For males, primary prevention should target the younger adults, whereas for females, it should target aged population.

Age-related decline in intrinsic capacity (IC), defined as the sum of an individual's physical and mental capacities, is a cornerstone for promoting healthy aging by prioritizing maintenance of function over disease treatment. However, assessing IC is resource-intensive, and the molecular and cellular bases of its decline are poorly understood. Here we used the INSPIRE-T cohort (1,014 individuals aged 20-102 years) to construct the IC clock, a DNA methylation-based predictor of IC, trained on...

Mice missing the complex I subunit Ndufs4 of the electron transport chain are widely used as a leading animal model of Leigh syndrome, a pediatric neurodegenerative disorder that leads to premature death. More broadly, this animal model has enabled a better understanding of the pathophysiology of mitochondrial disease and mitochondrial dysfunction in sporadic disorders. Intriguingly, longevity interventions are very effective at treating symptoms of disease in this model. Herein, we introduce...

Intrinsic Capacity (IC) is a crucial measure of the comprehensive physiological and psychological capabilities of older adults, playing a key role in assessing healthy aging. This systematic review aims to explore the trajectories of IC in older adults, as well as the associated determinants and health outcomes. By searching through PubMed, Embase, Ovid, and Web of Science databases, we identified 13 studies that met our inclusion criteria. To ensure the rigor of the review, the Newcastle-Ottawa...

Increased kinase activity of leucine-rich repeat kinase 2 (LRRK2) is associated with Parkinson's disease (PD). Numerous LRRK2-selective type I kinase inhibitors have been developed, and some have entered clinical trials. Here, to our knowledge, we present the first type II kinase inhibitors that target LRRK2. Targeting the inactive conformation of LRRK2 is functionally distinct from targeting the active-like conformation using type I inhibitors. We designed these inhibitors with a combinatorial...

The excitation-inhibition ratio is a key functional property of cortical microcircuits which changes throughout an individual's lifespan. Adolescence is considered a critical period for maturation of excitation-inhibition ratio. This has primarily been observed in animal studies. However, there is limited human in vivo evidence for maturation of excitation-inhibition ratio at the individual level. Here, we developed an individualized in vivo marker of regional excitation-inhibition ratio in...