Aging Effects on Osteoimmunology (R01 Clinical Trials Not Allowed)

This FOA seeks to support studies on normal and pathobiological changes in aging bone marrow that impact, or are impacted by, changes in immune function with age. Studies to be supported are in the field of osteoimmunology, which concerns the bidirectional interactions between bone and the immune system. The importance of osteoimmunology and its potential for improving the understanding of bone homeostasis is now recognized. However, most research has been conducted in young mice (3-4 months) that have not completed growth and development. Young animals cannot exhibit the relevant age-associated changes in immune function in the marrow niche that can best be revealed by comparison of older mice (at or older than 18 months) to young adult mice (at least 4 months of age). While important insights have been gained about osteoimmunological signaling pathways in the bone marrow niche of young adults, this approach has not addressed important questions more directly focused on age-related bone loss and the myriad of complex tissue interactions one expects, since bone is an endocrine organ. Pathobiological changes that occur in the aging marrow niche, such as myeloid skewing and declining immune function, are well-documented in the field of immunology. In addition, the role of T cells in osteoclast differentiation, bone resorption, and bone turnover have been demonstrated. However, many questions remain regarding how and why these changes occur over time in both healthy adults and older adults where bone loss is more commonly a major concern. The effect of age on healthy (adaptive) and pathobiological (maladaptive) changes that occur in the aging marrow niche and how these changes affect health trajectories in age-appropriate laboratory animals are the focus of this FOA.