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Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer's disease model
Despite strong evidence supporting the important roles of both apolipoprotein E4 (APOE4) and microglia in Alzheimer's disease (AD) pathogenesis, the effects of microglia on neuronal APOE4-related AD pathogenesis remain elusive. To examine such effects, we utilized microglial depletion in a chimeric model with induced pluripotent stem cell (iPSC)-derived human neurons in mouse hippocampus. Specifically, we transplanted homozygous APOE4, isogenic APOE3, and APOE-knockout (APOE-KO) iPSC-derived...
Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging
To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged...
ZNF652 exerts a tumor suppressor role in lung cancer by transcriptionally downregulating cyclin D3
Dysfunction of zinc finger protein 652 (ZNF652) is associated with various malignant tumors. However, the role of ZNF652 in lung cancer (LC) is poorly understood. Here, we identified that ZNF652 was downregulated in human LC tissues and cell lines. Low ZNF652 expression was associated with poor survival in LC patients. Overexpression of ZNF652 inhibited cell viability, proliferation, migration, and invasion of LC cells, whereas ZNF652 knockdown promoted these malignant phenotypes. Using RNA-seq...
Hypermethylation of CDKN2A CpG island drives resistance to PRC2 inhibitors in SWI/SNF loss-of-function tumors
Polycomb repressive complex 2 (PRC2) catalyzes the writing of the tri-methylated histone H3 at Lys27 (H3K27me3) epigenetic marker and suppresses the expression of genes, including tumor suppressors. The function of the complex can be partially antagonized by the SWI/SNF chromatin-remodeling complex. Previous studies have suggested that PRC2 is important for the proliferation of tumors with SWI/SNF loss-of-function mutations. In the present study, we have developed an EED-directed allosteric...
Phenome-wide associations of human aging uncover sex-specific dynamics
Aging varies significantly among individuals of the same chronological age, indicating that biological age (BA), estimated from molecular and physiological biomarkers, may better reflect aging. Prior research has often ignored sex-specific differences in aging patterns and mainly focused on aging biomarkers from a single data modality. Here we analyze a deeply phenotyped longitudinal cohort (10K project, Israel) of 10,000 healthy individuals aged 40-70 years that includes clinical,...
Interventions for improving health literacy among older people: a systematic review
CONCLUSION: Based on the findings, community-based interventions that encompass a one-dimensional approach, incorporating the use of technology and considering the duration of the intervention, are more recommended.
Association of cognitive performance with overall, dosage, intensity, and domain physical activity in aging: NHANES 2011-2014
CONCLUSIONS: Our results suggested a positive association between higher levels of PA and enhanced cognitive performance. Different intensities and domains of PA have varying impacts on cognition. Future exploration, such as objectively measured PA and longitudinal studies were needed to validate our conclusion.