Bone Marrow Transplantation from Young Donors Restores Neurogenesis and Motor Function in Middle Aged Mice

Age-related declines in cognitive and motor function are influenced by not only intrinsic changes within the brain but also systemic factors, including circulating blood components. Recent studies have suggested that the rejuvenation of the haematopoietic system may positively impact brain ageing. However, the effects of bone marrow transplantation (BMT) during middle age—prior to the onset of advanced deterioration—remain poorly understood. In this study, we addressed the effects of heterochronic BMT on motor and cognitive functions in 8-month-old mice conditioned with busulfan and transplanted bone marrow cells from either young (2-month-old) or age-matched donors. Behavioural testing and histological analyses were conducted three months post-transplantation. Compared with age-matched controls, mice receiving young bone marrow showed significantly improved neuromuscular strength and increased anxiety-like behaviour, although no differences in recognition memory were detected. Immunohistochemical analysis revealed a significant increase in doublecortin- and EdU-positive cells in the dentate gyri of young BMT mice, indicating enhanced adult neurogenesis. These findings suggest that haematopoietic rejuvenation via young BMT can partially restore neurogenesis and behaviour in middle-aged mice. Our study highlights the potential of systemic interventions targeting blood-derived factors as early therapeutic strategies for age-related neurological dysfunction.