Cellular senescence in the ageing brain: to eliminate or not to eliminate?

Senescent cells are damaged cells that no longer divide. They are present in aged human and mouse tissues. Here, they secrete pro-inflammatory molecules and promote various age-related dysfunctions and pathology. Removal of senescent cells however improves health span. Because it remains poorly understood how cellular senescence develops in the ageing brain, the goal of the research in this thesis was to gain more insight into brain senescence. The information hereby gained can help to develop therapeutic approaches aimed at preserving brain functions for a prolonged period of time. In chapter 1, an introduction to senescent cells in the brain is given. In chapter 2, the effect of the modulation of lysosomes, organelles that degrade damaged particles, in senescent cells was investigated. In chapter 3, single-cell gene expression profiling was used to identify distinct, age-dependent p16 expressing cell populations in the mouse brain. In chapter 4, the direct and indirect effect of genotoxic stress-induced senescence on glial cells in culture and in mice were characterized. In chapter 5, the data presented in chapters 2-4 are summarized, and future prospects in the area of basic and translational biology are discussed. In conclusion, the work presented here helps to elucidate the role of senescent cells and represents an important pillar for the characterization and targeting of brain senescence.