Excess Intracellular Cholesterol Provokes Macrophage Senescence
One of the key focuses at Repair Biotechnologies is the impact of excess intracellular cholesterol on aging. This pathological mechanism disrupts cell behavior and contributes to cell death. Removing excess cholesterol is challenging without engineered protein machinery or gene therapy. Excess cholesterol is a significant issue in aging, as highlighted in this research.
This study reveals that dysregulated cholesterol metabolism, influenced by metabolic and genotoxic stresses, leads to macrophage senescence. This process is mediated by the liver X nuclear receptor and CD38, causing NAD+ depletion. NAD+ augmentation reverses senescence and dysfunction in macrophages, protecting against age-related diseases like AMD.
Addressing the NAD+ deficit induced by excess intracellular cholesterol is crucial in preventing macrophage senescence and neurodegeneration. The findings suggest potential treatment strategies to combat AMD and other age-related conditions.
Link: https://doi.org/10.1016/j.celrep.2024.114102
