Grant: Travel Awards - Institute Community Support

As our cells age and undergo multiple rounds of cell division, they enter a state called replicative senescence where they are still viable and metabolically active but no longer able to proliferate. The accumulation of senescent cells in aged tissues impairs the regenerative capacity of human systems and contributes to many age-related chronic diseases such as arthritis, type II diabetes, and cancer. Despite the growing interest in developing therapies that target senescent cells, the molecular mechanisms which underlie cellular senescence are not fully understood. We have previously identified INhibitor of Growth 1 (ING1), the first member of the ING family of type II tumor suppressor proteins, which regulate critical cellular processes such as senescence, apoptosis, proliferation, and cell migration. ING1a, one of the isoforms of the ING1 gene, increases in both RNA and protein levels during replicative senescence. Overexpression of ING1a in primary fibroblasts itself causes a replicative senescence-like arrest with associated phenotypes, including senescence-associated beta-galactosidase staining. In order to understand the mechanisms by which ING1a functions during replicative senescence and cellular aging, I am using a mass spectrometry-based approach to identify binding partners which are specific to this gene isoform. Such genes will help us identify mechanisms of ING1a and replicative senescence and can be considered potential targets of intervention for age and senescence-associated disorders.