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Spatial and single-cell transcriptomics reveal the reorganization of cerebellar microglia with aging
The cerebellum, essential for motor coordination and increasingly recognized for its role in cognition, is typically considered more resilient to aging and largely spared from hallmark Alzheimer's disease (AD) pathology. However, transcriptomic analyses across fifteen mouse brain regions revealed that the cerebellum undergoes some of the earliest and most pronounced age-related changes. To investigate cerebellar aging, we applied single-nucleus RNA sequencing (RNA-seq), microglial bulk RNA-seq,...
Asymmetrical end structures of leading and lagging telomeres in Saccharomyces cerevisiae dictate the nature of the end replication problem
The end replication problem refers to incomplete replication of parental DNA at telomeres, a process whose molecular depiction is hampered by the complex nature of telomere ends. Here, we recapitulate this process using a synthetic de novo telomere in Saccharomyces cerevisiae and delineate distinct molecular fates of telomere ends in vivo. We show that the lagging-strand telomeres carry a ∼10 nt 3' overhang, while the leading-strand telomeres have a Yku-protected blunt end, a feature that is...
Spatial and single-cell transcriptomics reveal the reorganization of cerebellar microglia with aging
The cerebellum, essential for motor coordination and increasingly recognized for its role in cognition, is typically considered more resilient to aging and largely spared from hallmark Alzheimer's disease (AD) pathology. However, transcriptomic analyses across fifteen mouse brain regions revealed that the cerebellum undergoes some of the earliest and most pronounced age-related changes. To investigate cerebellar aging, we applied single-nucleus RNA sequencing (RNA-seq), microglial bulk RNA-seq,...
Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration
Aging or injury to the joints can lead to cartilage degeneration and osteoarthritis (OA), for which there are limited effective treatments. We found that expression of 15-hydroxy prostaglandin dehydrogenase (15-PGDH) is increased in the articular cartilage of aged or injured mice. Both systemic and local inhibition of 15-PGDH with a small molecule inhibitor (PGDHi) led to regeneration of articular cartilage and reduction in OA-associated pain. Using single cell RNA-sequencing and multiplexed...
Five reasons for the failure of frailty screening in primary care: lessons from the experience with ICOPE monitor step 1
CONCLUSIONS: The study highlighted the social and financial obstacles hindering the use of ICOPE Monitor and more broadly, the implementation of frailty screening by primary care practitioners.
Intracranial self-stimulation mitigates spatial task deficits, modifies miR-146a and miR-495 serum levels and restores hippocampal NRF2 levels in a rat model of sporadic Alzheimer's disease
CONCLUSION: Prolonged MFB-ICSS treatment mitigates cognitive deficits, modulates circulating levels of miRNA-495 and miR-146a, restores hippocampal NRF2 levels, and preserves corpus callosum integrity in the SAD rat model by STZ injection. These findings highlight the therapeutic potential of MFB-ICSS as a non-pharmacological intervention in AD. Furthermore, this study confirms NRF2 as a target of miR-495 in the context of AD.
Early-Life Climbing Stratifies the Metabolome and Mortality Risk in Genetically Identical Flies
Studies in laboratory organisms typically minimize all environmental and genetic variation other than the intervention of interest. In aging studies, these highly controlled conditions have yielded profound insights into aging. But even within isogenic cohorts of lab animals in controlled environments, we observe substantial variation in lifespan. Here we exploited the climbing behavior of Drosophila to study variation in mortality among isogenic populations in a controlled environment. We show...
Human Umbilical Cord Plasma Metabolomics Uncover Potential Metabolites for Combating Aging
Human umbilical cord blood (HUCB) exhibits distinct characteristics compared to adult blood, offering significant potential for medical applications, particularly in antiaging therapies. However, the metabolic profile of HUCB relative to adult blood remains poorly understood. Moreover, the specific metabolites within HUCB that confer antiaging properties have yet to be identified. Here, we conducted an untargeted metabolomic analysis comparing cord plasma and adult plasma. Our results reveal a...
Mathematics is hard for mathematicians to understand too
Science, Volume 390, Issue 6776, November 2025.
Erratum for the Policy Forum “How collaboration with China can revitalize US automotive innovation” by J. P. Helveston
Science, Volume 390, Issue 6776, November 2025.
Targeted protein degradation in the transmembrane and extracellular space
Science, Volume 390, Issue 6776, November 2025.
Active learning framework leveraging transcriptomics identifies modulators of disease phenotypes
Science, Volume 390, Issue 6776, November 2025.
Liquid-state dipolarcaloric refrigeration cycle with nitrate-based salts
Science, Volume 390, Issue 6776, November 2025.
Spectral kernel machines with electrically tunable photodetectors
Science, Volume 390, Issue 6776, November 2025.
Full utilization of noble metals by atom abstraction for propane dehydrogenation
Science, Volume 390, Issue 6776, November 2025.
Reranking partisan animosity in algorithmic social media feeds alters affective polarization
Science, Volume 390, Issue 6776, November 2025.
The dispersal of domestic cats from North Africa to Europe around 2000 years ago
Science, Volume 390, Issue 6776, November 2025.
Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals
Science, Volume 390, Issue 6776, November 2025.