G-quadruplex RNA and G-quadruplex RNA helicases in senescent neurons and astrocytes
Senescence is a homeostatic mechanism that prevents division of old or damaged cells and cancerous transformation. Besides permanent cell cycle arrest, senescent cells go through a number of observable changes such as a global repression of translation, chromatin rearrangement, metabolic reprogramming, specific epigenetic modifications, and morphological changes. A key feature of senescence is the senescence-associated secretory phenotype (SASP), which involves secretion of growth factors, cytokines, chemokines, and metalloproteinase that mediate non-cell-autonomous senescence effects. RNA (protein-coding, non-coding, etc.) is emerging as a critical regulator of cellular senescence, although molecular mechanisms of RNA-associated senescence are not clear. Our project will target molecular mechanisms that regulate G-quadruplex-RNA-associated aging in senescent astrocytes with a future goal for developing anti-senescence therapeutic interventions.