Volume 3 Issue 3, March 2023

Wang Lin and his colleagues explore how aging reprograms spatially unique pathways in liver endothelial cells to cause fibrosis. They find that loss of KIT in liver endothelial cells close to the central vein upregulates the chemokine receptor CXCR4 to stimulate inflammation, enhance fibrosis and increase lipid accumulation in aged liver.

Cellular senesence is believed to be a driver of aging. We designed and synthesized a photosensitive prodrug that destroys senescent cells by integrating multiple technologies that combine biomarker guidance with a fluorescence tag, target-site anchoring and photodynamic therapy, providing a strategy for monitoring and specifically eliminating senescent cells to regulate aging.

We found evolutionarily conserved astrocyte and microglia subpopulations shared across multiple brain regions. We reveal similarities and differences between Alzheimer’s disease glia and Parkinson’s disease glia, as well as regional variance linked to disease pathology and neurodegeneration.

Using samples and data from the CALERIE study, a human randomized controlled trial of long-term caloric restriction, the authors find that the intervention slows DunedinPACE, a DNA methylation measure of the pace of aging.

The authors show that liver sinusoidal endothelial cell (LSEC) senescence promotes steatosis by reprogramming liver endothelial zonation and inhibiting C-kit, a type III receptor tyrosine kinase. Infusing C-kit-expressing LSECs in aged or diet-induced NASH mice counteracts senescence and steatosis.

APOE4 is produced by neurons under stress, but the role of neuronal APOE4 in Alzheimer’s disease pathogenesis is still unclear. Here the authors report that selective removal of neuronal APOE4 in tauopathy mice mitigates many prominent Alzheimer’s disease-related pathologies.

Shi, Liu, Gao et al. present a strategy to monitor and selectively eliminate senescent cells in mice during aging through controllable photodynamic therapy, which inhibited the age-related functional decline.

By applying quantitative chemical cross-linking technologies, the authors show that changes in the mitochondrial interactome of the skeletal muscle contribute to mitochondrial functional decline in female mice.

Single-cell transcriptomic profiling of young and old mouse brains following heterochronic parabiosis shows regulation of several canonical hallmarks of aging by a shift in age-induced changes of the transcriptome in a cell-type-specific manner.

Zhao et al. find evolutionarily conserved astrocyte and microglia subpopulations shared across multiple brain regions and reveal similarities and differences between AD and PD glia and regional variance linked to AD pathology and neurodegeneration.