Pioneering anti-brain aging strategies based on novel regulatory system for neural activity

Elucidating the mechanisms for the decline of brain function with physiological aging and finding strategies to deter this decline will be major steps toward establishing preventive medicine that extends the healthy life span of the brain. However, the molecular mechanisms underlying the age-related decline in neurological function remain largely unknown.

We recently discovered that the nuclear envelope LINC complex, which is involved in cytoskeletal regulation, plays a pivotal role in regulating neural activity levels via the axon initial segment (AIS), a structure essential for the initiation of action potentials. Furthermore, we found that “LINC complex-mediated AIS regulation” is disrupted with aging in mice, leading to abnormal neural excitability and a consequent decline in brain function. In this study, we aim to elucidate the molecular mechanisms of “LINC complex-mediated AIS regulation” and its age-related disruption, thereby uncovering the core biological processes driving brain aging. We will also investigate whether preventing this disruption in aged mouse brains can mitigate the associated functional decline. Additionally, based on these insights, we will develop protein-engineered molecular tools with enhanced anti-aging effects and assess their efficacy in human-derived neurons.

This research is highly innovative in that it pioneers anti-aging interventions grounded in a well-defined molecular mechanism implicated in brain aging. The establishment of preventive medicine that enables older individuals to maintain “younger brain” will be of great value in shaping future societies by increasing the number of people who remain cognitively active in ever-changing new social systems.