Involvement of lipids in cellular senescence
MetadataShow full item record
Cellular senescence is a state of permanent cell-cycle arrest that occurs following an extended period of proliferation in culture or in response to stress. This phenomenon is characterized by dramatic morphological changes and specific metabolic and gene expression variations. Several studies have proposed that the senescence response evolved as a fail-safe mechanism to protect cells from cancer. Additionally, senescent cells have been shown to accumulate with age suggesting that senescence may contribute to organismal aging. Stress induced senescence occurs in response to DNA damage and has emerged as a potent cancer therapy where the tumor-suppressive potential of senescence could be used to aid in treating the disease. In the last couple of decades, considerable research efforts have been made towards understanding the protein machinery underlying senescence yet we still have a poor understanding of the role that lipids play in this phenomenon.The work presented in this dissertation focused on studying the role of lipids and membrane-related pathways in senescence. The lipid profiles of human proliferating and replicative senescent fibroblast cells were investigated via a liquid chromatography–mass spectrometry-based lipidomics approach. Our results show that triacylglycerols, neutral lipids, accumulate in human replicative senescent fibroblast cells. More specifically, triacylglycerol species that consist of long- and very long-chain fatty acids and contain at least one polyunsaturated fatty acyl chain accumulate during this process.