Chentao Li

Aging is characterized by systemic chronic inflammation, which is accompanied by cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there is an urgent need for a systematic organization of inflammaging through dimensionality reduction. Factors secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP), promote chronic inflammation and can induce senescence in normal cells. At the same time, chronic inflammation accelerates the senescence of immune cells, resulting in weakened immune function and an inability to clear senescent cells and inflammatory factors, which creates a vicious cycle of inflammation and senescence. Persistently elevated inflammation levels in organs such as the bone marrow, liver, and lungs cannot be eliminated in time, leading to organ damage and aging-related diseases. Therefore, inflammation has been recognized as an endogenous factor in aging, and the elimination of inflammation could be a potential strategy for anti-aging. Here we discuss inflammaging at the molecular, cellular, organ, and disease levels, and review current aging models, the implications of cutting-edge single cell technologies, as well as anti-aging strategies. Since preventing and alleviating aging-related diseases and improving the overall quality of life are the ultimate goals of aging research, our review highlights the critical features and potential mechanisms of inflammation and aging, along with the latest developments and future directions in aging research, providing a theoretical foundation for novel and practical anti-aging strategies.

Cellular immunotherapy has emerged as an exciting strategy for cancer treatment, as it aims to enhance the body's immune response to tumor cells by engineering immune cells and designing synthetic molecules from scratch. Because of the cytotoxic nature, abundance in peripheral blood, and maturation of genetic engineering techniques, T cells have become the most commonly engineered immune cells to date. Represented by chimeric antigen receptor (CAR)-T therapy, T cell-based immunotherapy has revolutionized the clinical treatment of hematological malignancies. However, serious side effects and limited efficacy in solid tumors have hindered the clinical application of cellular immunotherapy. To address these limitations, various innovative strategies regarding synthetic cells and molecules have been developed. On one hand, some cytotoxic immune cells other than T cells have been engineered to explore the potential of targeted elimination of tumor cells, while some adjuvant cells have also been engineered to enhance the therapeutic effect. On the other hand, diverse synthetic cellular components and molecules are added to engineered immune cells to regulate their functions, promoting cytotoxic activity and restricting side effects. Moreover, novel bioactive materials such as hydrogels facilitating the delivery of therapeutic immune cells have also been applied to improve the efficacy of cellular immunotherapy. This review summarizes the innovative strategies of synthetic cells and molecules currently available in cellular immunotherapies, discusses the limitations, and provides insights into the next generation of cellular immunotherapies.

Aging is considered a critical factor of poor prognosis in allogenic hemopoietic stem cell transplantation (allo-HSCT). To elucidate the underlying mechanisms, we comprehensively reintegrated our clinical data from patients after allo-HSCT and public single-cell transcriptomic profile from post-allo-HSCT and healthy individuals, demonstrating that old donors were more prone to acute GVHD (aGVHD) with pronounced inflammation accumulation and worse overall survival (OS). We also found the presence of inflammation-related CXCL2+ HSC subpopulation during aging with significantly enriched pro-inflammatory pathways. Shifting attention to the HSC microenvironment, we deciphered that IL-1/IL-6 and TRAIL (i.e., TNFSF10) ligand‒receptor pair serves as the crucial bridge between CD14/CD16 monocytes and hematopoietic stem/progenitor cells (HSPCs). The profound upregulation of these signaling pathways during aging finally causes HSC dysfunction and lineage-biased differentiation. Our findings provide the theoretical basis for achieving tailored GVHD management and enhancing allo-HSCT regimens efficacy for aged donors.