We are thrilled to announce the publication of a groundbreaking study titled “LXR/CD38 Activation Drives Cholesterol-Induced Macrophage Senescence and Neurodegeneration via NAD+ Depletion“, authored by Ryo Terao, MD, PhD; Mitsukuni Yoshida, MD, PhD; Rajendra Apte, MD, PhD; and colleagues from the Apte Lab.
In this study, our researchers unveil critical molecular mechanisms linking dysregulated cholesterol metabolism with inflammation and age-related diseases. Through their work, they discovered that metabolic and genotoxic stresses, mediated by the liver-X nuclear receptor, increase CD38 levels. This activation promotes the efflux of cholesterol from lysosomes, ultimately leading to a depletion of nicotinamide adenine dinucleotide (NAD+) in macrophages.
The depletion of NAD+ induces macrophage senescence, a key contributor to age-related macular degeneration (AMD), characterized by subretinal lipid deposition and neurodegeneration.
- Key Findings: The study reveals how excess cholesterol triggers a chain reaction that depletes a vital molecule called NAD+ in immune cells known as macrophages.
- Impact on Health: This NAD+ depletion drives macrophage senescence (cellular aging), a process linked to age-related diseases like macular degeneration (AMD), the leading cause of blindness in individuals over 60.
- Potential Therapeutic Approach: The study suggests that NAD+ augmentation could potentially reverse cellular senescence and macrophage dysfunction, offering a promising therapeutic strategy, particularly in the early stages of AMD.
This research represents a significant interdisciplinary effort, providing new insights into the interplay of aging, metabolism, and NAD+ biology. We anticipate that these findings will greatly advance our understanding of AMD and other age-related diseases.