Mulberroside A, naturally existent from the mulberry plant, is known for its diverse biological activities. Our research indicates that mulberroside A may possess significant anti-aging effects. We assessed its anti-aging properties using naturally aging animal models and by inducing senescence in human-derived endothelial cells and mouse-derived endothelial cells through treatment with angiotensin II. We found that mulberroside A promotes the proliferation of HMEC-1 and bEnd.3 endothelial cells, while significantly reducing the levels of senescence biomarkers p16, p21, and Rb in both these endothelial cell types and in the hippocampus, kidney, spleen and liver of naturally aging animals. Additionally, mulberroside A was found to mitigate telomerase depletion in the blood of naturally aging animals, enhance the body’s resistance ability to oxidative stress, and inhibit the overexpression of inflammatory factors in vivo.

Mitophagy clears damaged mitochondria and maintains normal macrophage function. Clarifying the associations between idiopathic pulmonary fibrosis (IPF), macrophages, and mitophagy is crucial for early diagnosis and clinical management. Core macrophage subsets were identified as M2 macrophages via single-cell RNA sequencing and immune infiltration analysis. Differentially expressed genes related to this subset were obtained. Integrated differential expression analysis, weighted gene co-expression network analysis, machine learning, and expression verification were applied to screen biomarkers. CD163 and SPP1 were identified through biomarker screening, both showing significantly increased expression in IPF. Functional enrichment showed that these biomarkers are mainly involved in cell cycle checkpoints and ciliopathies. Immune microenvironment analysis identified 16 immune cell types with significant differences between IPF and control groups, among which T helper 2 cells were strongly positively correlated with CD163. A total of nine drugs were found to be associated with CD163 and SPP1. The expression of these biomarkers changed dynamically during M2 macrophage differentiation. This study integrates single-cell and bulk transcriptomics analysis to reveal the critical roles of CD163 and SPP1 in the IPF macrophage–mitochondrial autophagy axis, a novel framework for understanding the macrophage–mitophagy axis in IPF pathogenesis.