title: Targeting metabolism in cellular senescence, a role for intervention.
abstract: Cellular senescence has gained much attention as a contributor to aging and susceptibility to disease. Senescent cells undergo a stable cell cycle arrest and produce pro-inflammatory cytokines. However, an additional feature of the senescence phenotype is an altered metabolic state. Despite maintaining a non-dividing state, senescent cells display a high metabolic rate. Metabolic changes characteristic of replicative senescence include altered mitochondrial function and perturbations in growth signaling pathways, such as the mTORC1-signaling pathway. Recent evidence has raised the possibility that these metabolic changes may be essential for the induction and maintenance of the senescent state. Interventions such as rapamycin treatment and methionine restriction impact key aspects of metabolism and delay cellular senescence to extend cellular lifespan. Here, we review the metabolic changes and potential metabolic regulators of the senescence program. In addition, we will discuss how lifespan-extending regimens prevent metabolic stress that accompanies and potentially regulates the senescence program.
authors: Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA 19102, USA.
authors: Timothy
authors: T
authors: Nacarelli
authors: Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA 19102, USA. Electronic address: Christian.sell@drexelmed.edu.
authors: Christian
authors: C
authors: Sell
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008715:Methionine / Q000008:administration & dosage / Q000172:deficiency; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D016207:Cytokines; D045222:Electron Transport Chain Complex Proteins; D008715:Methionine; D000076222:Mechanistic Target of Rapamycin Complex 1; D005947:Glucose; D020123:Sirolimus
keywords: Aging; Lifespan; Metabolism; Methionine restriction; Mitochondria; Rapamycin; Senescence; mTOR