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Clinical and genetic research links altered cholesterol metabolism with ALS development and progression, yet pinpointing specific pathomechanisms remain challenging. We investigated how cholesterol dysmetabolism interacts with protein aggregation, demyelination, and neuronal loss in ALS. Bulk RNAseq transcriptomics showed decreased cholesterol biosynthesis and increased cholesterol export in ALS mouse models (GA-Nes, GA-Camk2a GA-CFP, rNLS8) and patient samples (spinal cord), suggesting an...

Differentiating sequencing errors from true variants is a central genomics challenge, calling for error suppression strategies that balance costs and sensitivity. For example, circulating cell-free DNA (ccfDNA) sequencing for cancer monitoring is limited by sparsity of circulating tumor DNA, abundance of genomic material in samples and preanalytical error rates. Whole-genome sequencing (WGS) can overcome the low abundance of ccfDNA by integrating signals across the mutation landscape, but higher...

CONCLUSION: The core category,'Seniors on the margin of digital health literacy,'was selected to encompass the other seven categories.

CONCLUSION: This study identified the primary facilitators and barriers to community-based cognitive impairment management within the context of current policies. To enhance the effectiveness of interventions, policymakers, health departments, and community organizations should actively address the identified barriers and leverage the facilitators. Additionally, the findings provide valuable insights for other countries facing similar challenges in cognitive impairment management. Future...

RNA editing is a posttranscriptional mechanism that targets changes in RNA transcripts to modulate innate immune responses. We report the role of astrocyte-specific, ADAR1-mediated RNA editing in neuroinflammation in Parkinson's disease (PD). We generated human induced pluripotent stem cell-derived astrocytes, neurons and cocultures and exposed them to small soluble alpha-synuclein aggregates. Oligomeric alpha-synuclein triggered an inflammatory glial state associated with Toll-like receptor...

Neurodegenerative disorders such as Alzheimer's disease and macular degeneration represent major sources of human suffering, yet factors influencing disease severity remain poorly understood. Sex has been implicated as one modifying factor. Here, we show that female sex is a risk factor for worsened outcomes in a model of retinal degeneration and that this susceptibility is caused by the presence of female-specific sex hormones. The adverse effect of female sex hormones was specific to diseased...

In Arabidopsis, late endosome-localized ABNORMAL SHOOT 3 (ABS3) promotes senescence through a direct interaction with AUTOPHAGY8 (ATG8). However, the molecular mechanisms underlying the regulation of the ABS3-mediated senescence pathway are not well understood. Here, we report that HOOKLESS 1 (HLS1) acts as a negative regulator of plant senescence and the ABS3-mediated senescence pathway. We identify the localizations of HLS1 at the plasma membrane and endosomes in addition to the nucleus....

Telomere length regulation is essential for genome stability as short telomeres can trigger cellular senescence and apoptosis constituting an integral aspect of biological aging. Telomere biology disorders (TBDs) such as dyskeratosis congenita (DC) are rare, inherited diseases with known mutations in at least 16 different genes encoding components of the telomere maintenance complexes. The precise role of TEN1, part of the CST complex (CTC1, STN1, and TEN1), and the consequences of its loss of...

Preserving hematopoietic stem cell (HSC) functionality is essential for maintaining healthy blood and the immune system throughout life. HSC function declines with age; however, the underlying mechanisms are not fully understood. Using an inducible mosaic mouse model to overexpress the transcription factor Bcl11a in the hematopoietic compartment, we found that an aging-related increase in Bcl11a mitigated HSC functional decline, promoted IL-1β production in the bone marrow (BM), and accelerated...

BACKGROUND: As individuals experience age-related changes, such as cognitive decline or hospitalizations, their ability to live independently at home may be impacted. Decision-making and planning are essential in order to support successful aging-in-place (AIP), which is defined as continuing to live in one's home and community. Despite making plans at one single time-point, prior research has demonstrated that decision-making among older adults is not stagnant.

Vascular contributions to cognitive impairment and dementia (VCID) represent a major public health challenge in the aging population, with age-related cerebromicrovascular dysfunction playing a critical role in its development. Understanding the mechanisms underlying cerebromicrovascular aging is crucial for devising strategies to mitigate this burden. Among the key hallmarks of aging, genomic instability and genetic heterogeneity have emerged as significant drivers of age-related diseases....

Sleep disorders, particularly insomnia and obstructive sleep apnea, are increasingly implicated as significant contributors to cognitive decline, dementia, and neurodegenerative diseases such as Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID). However, the extent and specificity of these associations remain uncertain. This meta-analysis evaluates the impact of common sleep disorders on the risk of developing dementia and cognitive decline. A comprehensive search of...

CONCLUSIONS: Loneliness and social isolation among community-dwelling older adults are complex issues with profound implications for physical, mental, and social well-being. Addressing these challenges requires integrative approaches that consider individual, relational, and contextual factors. Further longitudinal and standardized research is needed to improve our understanding of the long-term impacts and effectiveness of interventions to mitigate these issues.

CONCLUSIONS: This study utilized a relatively large and highly representative sample of community-dwelling residents to identify factors associated with fractures in independent older adults. Even in independent older adults who were not certified as requiring long-term care, fractures were significantly associated with a decline in multiple health domains. These findings provide valuable insights that can inform efforts to promote healthy aging and reduce care dependency.

Social factors influence health outcomes and life expectancy. Individuals living in poverty often have adverse health outcomes related to chronic inflammation that affect the cardiovascular, renal, and pulmonary systems. Negative psychosocial experiences are associated with transcriptional changes in genes associated with complex traits. However, the underlying molecular mechanisms by which poverty increases the risk of disease and health disparities are still not fully understood. To bridge the...

Identifying factors affecting lifespan, including genes or proteins, enables effective interventions. We prioritized potential drug targets and provided insights into biological pathways for healthy longevity by integrating Mendelian randomization, cohort, and experimental studies. We identified causal effects of tissue-specific genetic transcripts and serum protein levels on three longevity outcomes: the parental lifespan, the top 1% and 10% extreme longevity, utilizing Mendelian randomization...

CONCLUSION: Social participation not only directly improves cognitive function but also indirectly enhances it by reducing depression and increasing grandchild caregiving engagement among middle-aged and elderly individuals. However, while the mediating effect of grandchild care is statistically significant, its effect size remains relatively small, suggesting that its overall contribution to cognitive function should be interpreted with caution. In contrast, depression demonstrates a more...

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In latest xenotransplant test, Towana Looney’s body rejects gene-edited organ after more than 4 months

Sudden move mirrors NIH cap on “indirect” costs that was ruled illegal