Aging and immune rejuvenation: Mechanistic insights into restoring lymphoid potential in elderly hematopoietic progenitors

With the global population aged 65+ projected to double by 2050, understanding and reversing immune aging has become one of the most pressing challenges in biomedical research. Immunosenescence - the progressive deterioration of immune function with age - contributes to increased susceptibility to infections, reduced vaccine efficacy, and higher rates of cancer and autoimmune dysregulation. Central to this decline is the reduced capacity of aged hematopoietic progenitors to generate functional lymphoid cells, alongside thymic involution, T cell exhaustion, and inflammaging.

Despite significant advances, major gaps remain: the molecular checkpoints controlling lymphoid fate in aging, the role of niche signals in restraining or enabling immune regeneration, and the challenge of translating promising preclinical interventions into clinical strategies. Emerging tools - single-cell multi-omics, in vivo lineage tracing, gene editing, and metabolic reprogramming - are now accelerating discovery across these fronts.

This Research Topic invites mechanistic and translational contributions from researchers working across the full spectrum of immune aging, including but not limited to:

- Age-related changes in hematopoietic stem and progenitor cell biology

- Epigenetic and transcriptional regulation of lymphoid fate in aging

- Thymic involution and strategies for functional thymic restoration

- T cell, B cell, and NK cell aging - phenotype, function, and rejuvenation

- Inflammaging, chronic immune activation, and systemic immune remodelling

- Metabolic and niche-based interventions to restore immune competence

- Single-cell and multi-omics approaches to dissect immune aging

- Translational strategies: improving vaccination, infection resistance, and cancer immunosurveillance in elderly populations

- Clinical trials and human cohort studies in immunogerontology