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Regulation of Protein Turnover by Longevity Pathways

  • Tibor Vellai
  • Krisztina Takács-Vellai
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 694)

Abstract

Cellular homeostasis, which is needed for the cells to survive, requires a well-controlled balance in protein turnover. Both protein synthesis and degradation are influenced by distinct genetic pathways that control aging in divergent eukaryotic species. These conserved mechanisms involve the insulin/IGF-1 (Insulin-like Growth Factor-1), TGF-β (Transforming Growth Factor-β), JNK (c-Jun terminal kinase), RTK/Ras/MAPK (Receptor Tyrosine Kinase/ Ras/Mitogen-Activated Protein Kinase) and TOR (kinase Target Of Rapamycin) signaling cascades and the mitochondrial respiratory system—each of them promotes protein synthesis; as well as the intracellular protein degradation machineries, including the ubiquitin-proteasome system and lysosome-mediated autophagy. In addition to providing building blocks for generation of new proteins and fuelling the cell with energy under starvation, the protein degradation processes eliminate damaged, nonfunctional proteins, the accumulation of which serves as the primary contributory factor to aging. Interestingly, a complex, intimate regulatory relationship exists between mechanisms promoting protein synthesis and those mediating protein degradation: under certain circumstances the former downregulate the latter. Thus, conditions that favor protein synthesis can enhance the rate at which damaged proteins accumulate. This may explain why genetic interventions and environmental factors (e.g., dietary restriction) that reduce protein synthesis, at least to tolerable levels, extend lifespan and increase resistance to cellular stress in various experimental model organisms of aging. In this chapter, the molecular mechanisms by which protein synthesis-promoting longevity pathways and protein degradation pathways interact with each other are discussed.

Keywords

Tuberous Sclerosis Complex Protein Turnover mRNA Translation Evity Pathway Replicative Life Span 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Department of GeneticsEötvös Loránd University, Pázmány Péter stny. 1/C.BudapestHungary

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