As a significant global issue, aging is prompting people’s interest in the potential anti-aging properties of Anoectochilus roxburghii (A. roxburghii), a plant traditionally utilized in various Asian countries for its purported benefits in treating diabetes and combating aging. However, the specific anti-aging components and mechanisms of A. roxburghii remain unclear. This study aims to investigate the anti-aging effects and mechanisms of A. roxburghii extract E (ARE). Caenorhabditis elegans (C. elegans) were exposed to media containing different concentrations of ARE whose superior in vitro radical scavenging capacity was thus identified. Lifespan assays, stress resistance tests, and RT-qPCR analyses were conducted to evaluate anti-aging efficacy, reactive oxygen species (ROS) levels, antioxidant enzyme activity, and daf-16, sod-3, and gst-4 levels. Additionally, transcriptomic and metabolomic analyses were performed to elucidate the potential anti-aging mechanisms of ARE. Fluorescence protein assays and gene knockout experiments were employed to validate the impacts of ARE on anti-aging mechanisms. Our results revealed that ARE not only prolonged the lifespan of C. elegans but also mitigated ROS and lipofuscin accumulation, and boosted resistance to UV and heat stress. Furthermore, ARE modulated the expression of pivotal anti-aging genes including daf-16, sod-3, and gst-4, facilitating the nuclear translocation of DAF-16. Significantly, ARE failed to extend the lifespan of daf-16-deficient C. elegans (CF1038), indicating its dependency on the daf-16/FoxO signaling pathway. These results underscored the effectiveness of ARE as a natural agent for enhancing longevity and stress resilience to C. elegans, potentially to human.

Vascular calcification (VC) is an actively regulated pathological process that significantly increases the risk of cardiovascular events. As key cells of the innate immune system, macrophages play a dual role in VC through polarization into different phenotypes: Pro-inflammatory macrophages promote calcification by secreting pro-inflammatory factors, releasing apoptotic bodies, and producing extracellular vesicles (EVs); conversely, Anti-inflammatory macrophages inhibit calcification through anti-inflammatory factors, exosomes, plaque stabilization, and ATP/pyrophosphate (PPi) metabolism. However, under metabolic diseases such as diabetes, anti-inflammatory macrophages may exhibit pro-calcific properties. This review systematically summarizes the mechanisms of macrophage polarization in VC, discusses the application of macrophage-related biomarkers and imaging techniques in diagnosis, and highlights therapeutic strategies targeting macrophage polarization, recruitment, and activation. Finally, current challenges in dynamically monitoring macrophage polarization and context-dependent functional heterogeneity are outlined, and future research directions focusing on immunomodulation-based multi-target drug design and engineered cell therapies are proposed.

Vascular calcification is an ectopic calcium salt deposition process that lacks effective treatment under pathological conditions such as chronic kidney disease, diabetes, and aging. This review, for the first time, systematically categorizes miRNAs involved in the regulation of vascular calcification according to signaling pathways, clearly revealing the regulatory nodes and crosstalk among different pathways (Wnt/β catenin, BMP/Smad, NF κB, etc.), thereby providing a pathway-level theoretical basis for precision targeting. It also dissects the functional duality and microenvironment dependency of miRNAs—the same miRNA can exert opposite effects in different contexts, suggesting that miRNA-based drug development must focus on disease-selective targeted delivery to avoid the risk of functional reversal. This article further comprehensively summarizes the heterogeneous regulatory patterns of lncRNAs, the unique regulatory modes of circRNAs, and preliminary evidence suggesting the involvement of emerging non-coding RNAs (piRNAs, tsRNAs) and integrates the potential of circulating non-coding RNAs as non-invasive biomarkers and prospects for targeted therapeutic translation. This review provides a panoramic view of the network-based regulation of vascular calcification by non-coding RNAs, laying a theoretical foundation for precision diagnosis and multi-target combination intervention.