Is Impaired Proteodynamics a Key to Understand the Biomarkers of Human Cellular Aging?
Current understanding of the fates of cellular proteins during aging is fragmentary and far from complete. The attention of researchers in the field is on the process of proteostasis, aiming at detection and elimination of misfolded and aggregated proteins. In this chapter we discuss other aspects of the protein behavior during cellular aging, from translation to various posttranslational modifications to limited degradation, together defined as proteodynamics. We argue here that the quantitative and qualitative effects of changed proteodynamics in the aging cells may be at least the biomarkers of aging and the aging-related diseases including but not limited to chronic inflammation, cardiovascular, neurodegenerative, chronic kidney disease, type 2 diabetes mellitus and sarcopenia, or even constitute causative factors in both cellular aging and these ARDs. As an illustration we describe in detail the properties and roles of ubiquitous neutral cytoplasmic proteases—calpains, performing the limited proteolytic modification of multiple substrates and involved in the above mentioned pathologies and in cellular aging.
KeywordsCellular aging Proteostasis Proteodynamics Posttranslational modification Calpain-calpastatin system Lymphocytes Aging-related diseases
This work was supported by the Polish Ministry of Science and Higher Education statutory grant 02-0058/07/262 to JMW.
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