Core Viewpoint - The article discusses a breakthrough in reversing immune aging through mRNA technology, which allows the liver to temporarily act as a "protein factory" to produce three key immune nutritional factors, enhancing immune responses in aged mice [1][2]. Group 1: Immune Aging and Its Challenges - Aging leads to significant changes in the immune system, including thymic shrinkage and reduced T cell production, resulting in decreased immune diversity and response to pathogens and cancer [4]. - Traditional methods to reverse immune aging, such as hormone therapy and cytokine injections, have shown limited effectiveness and often come with side effects [5][6]. Group 2: Innovative Approach - The research team utilized multi-omics analysis to identify weakened immune signaling pathways in aged mice, specifically the Notch, FLT3L, and IL-7 pathways, which are crucial for T cell development and function [8]. - A liver DFI reconstruction strategy was designed, encapsulating mRNA coding for DLL1, FLT3L, and IL-7 in lipid nanoparticles (LNP) for intravenous injection targeting the liver, which retains good function even in old age [8]. Group 3: Remarkable Outcomes - Post-treatment, aged mice exhibited significant thymic regeneration, increased new T cell numbers, and improved T cell receptor diversity, indicating a rejuvenation of the immune system [11]. - The treated aged mice showed a twofold increase in antigen-specific T cell numbers and response intensity to vaccines, nearing levels seen in younger mice [12]. - In tumor models, 40% of treated aged mice completely cleared tumors, while all control mice died due to tumor progression, indicating enhanced anti-tumor capabilities [14]. Group 4: Safety and Reversibility - The therapy is characterized by its safety, as effects diminish after treatment cessation, avoiding long-term uncontrolled risks. In models prone to spontaneous diabetes, the treatment did not accelerate disease progression, indicating it does not disrupt immune tolerance [18]. - Compared to traditional recombinant cytokine therapies, the mRNA approach resulted in significantly reduced systemic inflammatory responses and maintained normal liver and kidney function indicators, showcasing better safety profiles [19]. Group 5: Future Prospects - This research highlights the potential of using the liver for therapeutic protein production, which could serve as a universal strategy against age-related diseases, including cancer [21]. - The method's adjustability and reversibility allow for precise control over treatment duration, and it may be applicable to other key factors diminished by aging, offering new insights for various age-related diseases [21][22]. - The study opens new paradigms for systemic treatment through organ-specific delivery, providing innovative solutions to combat immune aging [23].