Abstract
Lipids are key macromolecules that perform a multitude of biological functions ranging from maintaining structural integrity of membranes, energy storage, to signaling molecules. Unsurprisingly, variations in lipid composition and its levels can influence the functional and physiological state of the cell and its milieu. Cellular senescence is a permanent state of cell cycle arrest and is a hallmark of the aging process, as well as several age-related pathologies. Senescent cells are often characterized by alterations in morphology, metabolism, chromatin remodeling and exhibit a complex pro-inflammatory secretome (SASP). Recent studies have shown that the regulation of specific lipid species play a critical role in senescence. Indeed, some lipid species even contribute to the low-grade inflammation associated with SASP. Many protein regulators of senescence have been well characterized and are associated with lipid metabolism. However, the link between critical regulators of cellular senescence and senescence-associated lipid changes is yet to be elucidated. Here we systematically review the current knowledge on lipid metabolism and dynamics of cellular lipid content during senescence. We focus on the roles of major players of senescence in regulating lipid metabolism. Finally, we explore the future prospects of lipid research in senescence and its potential to be targeted as senotherapeutics.
Highlights
Senescence is a cell-fate decision that is triggered in response to many different stressors including genotoxic stress, telomere attrition/damage, oncogene activation, and mitochondrial dysfunction (Herranz and Gil, 2018)
We review the link between major regulators of senescence and their role in lipid metabolism
During replicative senescence in myoblasts, several acylcarnitines were increased, suggesting that senescent cells rely heavily on β-oxidation (Baraibar et al, 2016). These senescent myoblasts had increased levels of monoacyl glycerols and glycerol-3-phosphate, as well as decreased monoand polyunsaturated long chain fatty acids (>18 carbons), whereas medium chain fatty acids remained unaffected. This suggests that senescent cells increase lipid breakdown, whether this lipid mobilization and breakdown is used for energy production, gene transcription or generation of senescence associated secretory program (SASP) is unclear
Summary
Reviewed by: Anthony Donato, The University of Utah, United States Gunes Ekin Atilla-Gokcumen, University at Buffalo, United States. Variations in lipid composition and its levels can influence the functional and physiological state of the cell and its milieu. Senescent cells are often characterized by alterations in morphology, metabolism, chromatin remodeling and exhibit a complex pro-inflammatory secretome (SASP). Recent studies have shown that the regulation of specific lipid species play a critical role in senescence. Many protein regulators of senescence have been well characterized and are associated with lipid metabolism. The link between critical regulators of cellular senescence and senescenceassociated lipid changes is yet to be elucidated. We systematically review the current knowledge on lipid metabolism and dynamics of cellular lipid content during senescence. We focus on the roles of major players of senescence in regulating lipid metabolism. We explore the future prospects of lipid research in senescence and its potential to be targeted as senotherapeutics
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