Immunology of longevity: T cell stemness, renewal dynamics, and systems-level regulation

The field of immunology of ageing is rapidly evolving, with T cells playing a pivotal role in maintaining immune competence and overall organismal resilience over the human lifespan. Evidence increasingly points to T cell populations—spanning progenitors, stem-like, naïve, and memory subsets—as essential mediators of immunological surveillance, repair, and adaptability during ageing. While stemness and renewal are fundamental to T cell longevity, ongoing questions persist about how age-associated changes such as thymic involution, chronic antigen exposure, metabolic shifts, and cellular senescence affect T cell homeostasis, functionality, and the body’s capacity for immune protection. Recent studies utilizing advanced single-cell and multi-omics technologies have begun to unravel how longevity hinges on the plasticity, persistence, and adaptability of T cell compartments. Nevertheless, the translation of these findings into broader mechanistic principles and therapeutic interventions remains an area of crucial importance, as many molecular and systems-level processes governing long-term immune health are not yet fully characterized.This Research Topic aims to comprehensively elucidate the cellular and systems-level mechanisms underpinning T cell renewal, stemness, and immune regulation in the context of longevity. The objective is to uncover how intrinsic T cell programs, interleukin-driven signaling, transcriptional control, and peptide–MHC dynamics converge to maintain—or erode—immunological fitness over time. Central questions include determining the molecular drivers of sustained T cell function across the lifespan, the dynamics of clonal turnover, mechanisms of exhaustion and rejuvenation, and the systemic orchestration of immunological memory and resilience. By harnessing interdisciplinary approaches—including computational modeling, multi-omics integration, and synthetic biology—the Research Topic seeks to develop predictive and actionable frameworks for enhancing immune longevity.This Research Topic integrates molecular, cellular, and systems immunology, focusing on fundamental as well as translational aspects of T cell biology in ageing and longevity. While the emphasis lies on immunological processes rather than purely clinical observations, submissions spanning basic mechanistic research to engineered therapeutic strategies are encouraged. To gather further insights into the immunology of longevity, we welcome articles addressing, but not limited to, the following themes:-Stem-like T cell programs and their role in long-term immune maintenance-Mechanisms governing differentiation, renewal, and reversal of cellular senescence in T cells-Age-related alterations in antigen presentation, TCR signaling, and co-receptor dynamics-Transcriptional and metabolic regulation underlying T cell persistence and function-Multi-omics and computational approaches to model age-associated immune decline-Systems-level analyses of immune homeostasis, renewal, and network adaptation with age-Strategies in synthetic immunology to rejuvenate or reprogram immune function for healthy ageingWe invite Reviews, Mini-Reviews, Original Research, Perspectives, and Methods papers that deliver mechanistic, multi-layered insights relevant to T cell biology and systems immunology. Submissions should focus on integrated molecular, cellular, and systems perspectives to expand the emerging field of the Immunology of Longevity and inform strategies for extending immune health and lifespan. Dr. Anthony founded Quorimmune, an immunological biotech company; Dr. Christos is an Advisor to Quanta (maker of home dialysis equipment) and a holder of patent for RNA sequencing protocol (managed by the University of New Mexico Tech Transfer Office - no royalties have been received) Topic editors: Anthony Joseph Leonardi, Christos Argyropoulos, Marsha Wills-Karp Source: https://www.frontiersin.org/research-topics/76444/immunology-of-longevity-t-cell-stemness-renewal-dynamics-and-systems-level-regulation