Regulation of protein turnover by longevity pathways

Research output: Chapter

24 Citations (Scopus)

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- (Transforming Growth Factor-), 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.

Original languageEnglish
Title of host publicationProtein Metabolism and Homeostasis in Aging
EditorsNektarios Tavernarakis
Pages69-80
Number of pages12
DOIs
Publication statusPublished - dec. 1 2010

Publication series

NameAdvances in Experimental Medicine and Biology
Volume694
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Vellai, T., & Takács-Vellai, K. (2010). Regulation of protein turnover by longevity pathways. In N. Tavernarakis (Ed.), Protein Metabolism and Homeostasis in Aging (pp. 69-80). (Advances in Experimental Medicine and Biology; Vol. 694). https://doi.org/10.1007/978-1-4419-7002-2_7