Core Viewpoint - The article discusses the relationship between aging and the immune system, emphasizing how immune responses change with age and the potential for manipulating immune function to extend healthy lifespan [2][24]. Group 1: Aging and Immune Response - Aging leads to significant changes in immune cell function, including a bias towards myeloid output from bone marrow, accumulation of senescent T cells, and increased levels of systemic inflammatory cytokines [6][24]. - The immune system is increasingly recognized as a key regulator of systemic aging, potentially driving the aging process rather than merely responding to it [24]. Group 2: Mitochondrial Function and Immune Aging - Mitochondrial dysfunction is central to immune aging, as age-related decline in mitochondrial function weakens immune responses and promotes chronic inflammation [7][8]. - Mitochondria also play a role in systemic signaling, influencing immune responses across different tissues, which is often overlooked in current models of immune aging [7][8]. Group 3: Spaceflight as a Model for Aging - Research using spaceflight environments reveals that many immune changes observed in aging, such as increased inflammatory mediators and impaired adaptive immune responses, can also occur in microgravity [9][12]. - This suggests that spaceflight can serve as a valuable model for studying the mechanisms of immune aging [9][12]. Group 4: Vaccine Response in the Elderly - Elderly individuals typically exhibit lower antibody titers and fewer memory B cells post-vaccination, leading to impaired protective immune responses [14]. - Recent findings indicate that the germinal center response in older adults can be enhanced, paving the way for improved vaccine strategies tailored to aging populations [14]. Group 5: T Cell Changes with Age - Aging is associated with various changes in T cells, including reduced diversity in T cell receptor repertoires and a shift towards inflammatory phenotypes [15][16]. - Understanding whether these changes are adaptive or degenerative is crucial for developing therapeutic strategies targeting age-related immune dysfunction [15][16]. Group 6: Personalized Immunotherapy - The potential of immune modulation in treating diseases is significant, with a focus on how aging affects the efficacy of immunotherapies like CAR-T cell therapy [19]. - Tailoring immunotherapy strategies based on age-related changes in immune cell function could enhance treatment outcomes across different age groups [19]. Group 7: Future Directions in Aging Research - The field must transition from defining aging processes to developing interventions, including identifying biomarkers and strategies to selectively target pathological aging cells [21]. - Integrating artificial intelligence with systems immunology could provide new insights into the regulatory nodes of immune aging, potentially allowing for interventions that recalibrate immune responses to slow aging [24][21].

Core Viewpoint - The article discusses the advancements in in vivo CAR-T cell therapy, particularly focusing on a new type of lipid nanoparticle (LNP) that does not require antibody modification, which enhances the delivery of circRNA-based CAR-T cells for treating inflammatory aging diseases [1][2][3][5]. Group 1: In Vivo CAR-T Therapy Advantages - In vivo CAR-T therapy, based on mRNA, offers significant advantages over traditional ex vivo CAR-T therapy, especially in treating inflammatory aging diseases [6][14]. - The transient expression of in vivo CAR-T cells may be beneficial for inflammatory aging, contrasting with its potential drawbacks in solid tumor treatments [6][14]. Group 2: Research Innovations - The research team developed a novel type of LNP inspired by cardiolipin, which enhances T cell targeting without the need for antibody modification [8][15]. - The study demonstrated that the CAMP lipid increases the stiffness and phase separation of LNPs, improving T cell uptake [9][15]. Group 3: CircRNA Utilization - The research utilized circRNA to modify CAR mRNA, enhancing its stability and reducing cytotoxicity, which prolongs CAR protein expression in vivo [10][15]. - The encapsulation of CAR mRNA targeting uPAR in PL40-LNP provides a proof of concept for treating liver fibrosis and rheumatoid arthritis [11][12]. Group 4: Clinical Implications - The study highlights the potential of non-antibody targeting strategies in developing in vivo CAR-T therapies for clearing senescent cells associated with inflammatory aging diseases [17].