Cologne Seminars on Ageing "Exploring long-lived cellular components for neural plasticity and brain aging"

About Tomohisa's talk:

Ageing is one of the major risk factors for neurological and psychiatric disorders. However, the biological links between
physiological ageing and pathological development are still largely unknown. To tackle this problem, our group has been
investigating the role of nuclear structural proteins in the brain, such as lamins and nucleoporins. These structural proteins are known to be long-lived but also targets of aging. We found that these stable structural proteins are critical for organizing cell typespecific epigenome in somatic neural stem cells and maintaining brain function. We also investigated their role in post-mitotic neurons, and found that Nup153, one of the nucleoporins, acts as a gatekeeper for neuronal responsiveness by regulating neural plasticity-related gene expression, which is a fundamental process for maintaining neural plasticity.
In addition to long-lived proteins, we have explored other long-lived cellular components and found that some of RNAs that do not turnover in the mouse brain for 2 years. These extremely long-lived RNAs (LL-RNAs) were retained in the nuclei in a cell type–specific manner. Perturbation experiments revealed that one of the LL-RNAs is required for heterochromatin maintenance quiescent neural stem cell reactivation, suggesting their functional importance in maintaining somatic stem cell function.