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Partial reprogramming has emerged as a promising strategy to reset the epigenetic landscape of aged cells towards more youthful profiles. Recent advancements have included the development of chemical reprogramming cocktails that can lower the epigenetic and transcriptomic age of cells and upregulate mitochondrial biogenesis and oxidative phosphorylation. However, the ability of these cocktails to affect biological age in a mammalian aging model has yet to be tested. Here, we have characterized...

The geroscience hypothesis suggests that understanding mechanisms underlying aging will enable us to delay and lessen age-related disability and diseases. The role of mechanical factors has been increasingly appreciated in many aspects of the aging process. Here, we use mouse models to investigate changes in the biomechanics of the proximal pulmonary artery, lung function, and right ventricle function in aging. We found an age-related decreased capacity to store energy and increased...

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Alzheimer's disease (AD) remains a major unmet medical challenge, with limited tools that integrate early diagnosis and therapeutic intervention. Considering the pivotal roles of amyloid-β (Aβ) and cholinesterases (ChEs) in AD etiology, we report dual-functional theranostic NIR-I probes. The lead candidate, I-43, exhibits favorable NIR optical properties (Stokes shift ≥ 220 nm) and binds strongly to Aβ fibrils, with K(d) values of 58.2 ± 9.7 nM for Aβ(1-40) and 104 ± 25 nM for Aβ(1-42)....

CONCLUSIONS AND IMPLICATIONS: This study demonstrates that multiple falls are a significant predictor of future dementia and highlights the importance of fall frequency. Recurrent falls may serve as a potential clinical marker for identifying individuals at higher risk. Clinicians should maintain heightened vigilance for cognitive decline in middle-aged and older adults with a history of recurrent falls to facilitate early detection of dementia. Given the limited evidence base and high...

Cognitive and psychiatric comorbidities are among the most persistent and disabling challenges experienced by children and adults with epilepsy, with serious implications for daily functioning, health-care utilization, long-term social outcomes and quality of life. Traditionally, research has focused on epilepsy-specific biological risk factors, such as seizure frequency or epilepsy syndrome, but growing evidence indicates that non-medical factors also shape neurodevelopmental, cognitive and...

CONCLUSION: Trajectories of total depressive symptoms marked by escalation, instability, or sustained elevation exhibited significantly elevated stroke risk. In contrast, individuals displaying decreasing depressive symptoms exhibit stroke risk comparable to those maintaining consistently low levels. Specifically, an ascending trajectory of cognitive-affective symptoms, alongside unstable and persistently elevated trajectories of somatic symptoms, are linked to increased stroke risk. These...

CONCLUSION: This study provides the first integrative single-cell transcriptomic map of microglial-myeloid interactions after TBI across multiple tissues and time points, linking microglial signaling to mitochondrial dysfunction and neuroinflammation. These findings lay the foundation for therapeutic strategies targeting myeloid-driven immune regulation in TBI.

Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most significant health challenges of aging, characterized by progressive cognitive and motor decline. Increasing evidence suggests that these conditions are not inevitable outcomes of aging but may instead be driven by preventable mechanisms involving oxidative stress, chronic inflammation, and disruptions in homeostasis. This manuscript proposes a preventive framework that integrates...

Neuronal aging and neurodegenerative diseases are accompanied by proteostasis collapse, while the cellular factors that trigger it have not been identified. Impaired mitochondrial transport in the axon is another feature of aging and neurodegenerative diseases. Using Drosophila, we found that genetic depletion of axonal mitochondria causes dysregulation of protein degradation. Axons with mitochondrial depletion showed abnormal protein accumulation and autophagic defects. Lowering neuronal ATP...