• Protein Homeostasis and Aging
  • Atena Zandi,1,* Saba Jafari,2
    1. Islamic Azad Medical University of Tehran
    2. Islamic Azad Medical University of Tehran


  • Introduction: All cells rely on specific processes to control protein homeostasis in order to preserve a steady and useful proteome. As dysfunction in protein homeostasis, or proteostasis, is a universal hallmark of both the aging process and cancer. The cellular quality control is maintained by proteolytic systems and molecular chaperones, which guarantee the constant synthesis of intracellular proteins. The pool of all sorts of proteins found inside cells and in their plasma membrane is known as the cellular proteome, and it is strictly regulated to ensure that each protein is synthesized, folded, and sub compartmentalized as intended.changes in different components of the protein quality control systems have been shown to underlie the basis of some human diseases, which are generally known as protein conformational disorders, and which include pathologies such as neurodegenerative diseases, metabolic disorders, myopathies, liver diseases and systemic disorders type amyloidosis. The term "proteotoxicity" is currently used to describe the toxic effects of altered proteins in cells. Protein unfolding, abnormal cleavage or undesirable post translational modifications can all promote protein self-assembling into toxic oligomeric structures oraggregation into cytosolic inclusions, often bringing along other proteins. Lifespan extension is nearly always linked to resistance to environmental stress, such as oxidative, thermal, and osmotic stress, and the processes managing protein homeostasis are essential for cellular adaptation to stress. Various internal and external stresses that persist throughout life can disrupt protein homeostasis in organisms. oxidative damage to proteins plays a crucial role in accelerating aging.
  • Methods: Protein homeostasis and the major gate-keepers Chaperones are necessary for covering hydrophobic regions and preventing unwanted non-specific protein binding during these processes. Chaperonins, a subset of cellular chaperones, are more active because they provide a little chamber or microenvironment that helps proteins fold or refold away from the intracellular milieu that promotes aggregation. The "gate keepers" or primary effectors in protein quality control are therefore chaperones and intracellular proteolytic mechanisms. Molecular Chaperones in protein quality control When exposed to high temperatures and other stressors, stress factors known as molecular chaperones or heat shock proteins (HSP) are quickly produced. Chaperones can be divided into five main types based on their molecular weight: The small heat shock proteins (sHSP) and HSP100, HSP90, HSP70, and HSP60 Cytosolic chaperones This group of chaperones regulates cytosol folding and unfolding events, primarily involving proteins from polysomes or other compartments, to prevent luminal cloggin. The ubiquitin/proteasome system and lysosomes, the two main proteolytic systems in this compartment, are intimately related to the role of cytosolic chaperones in quality control.
  • Results: Organelle-specific chaperones The ER chaperones that are in charge of maintaining protein homeostasis have the best characterised roles as organelle chaperones in quality control. The ER's protein homeostasis-maintaining organelle chaperones have the best documented roles in quality control. Molecular chaperones in longevity and aging Increasing chaperone induction has been shown in numerous studies to extend the lifespan of both unicellular and multicellular organisms. Flies and worms carrying extra copies of an hsp-70 family member or sHSPs have been shown to be long-lived The inability of HSF to bind the heat shock element on the chaperone gene promoter has been identified as the cause of the failure of chaperone transcription to upregulate with ageing, at least in the case of hsp70. . Proteolytic systems This system consists of The ubiquitin/proteasome system which is is one of the main proteolytic systems that participate in protein quality control.
  • Conclusion: Protein quality control is essential for proper cellular function and in the orchestration of an efficient cellular response to stress. Growing evidence supports that functional decline of the different components of the proteostasis network is one of the essential factors that contribute to cellular and organism aging. Protein quality control is essential for proper cellular function and in the orchestration of an efficient cellular response to stress. Growing evidence supports that functional decline of the different components of the proteostasis network is one of the essential factors that contribute to cellular and organism aging. How aging affects this cross-talk and whether functional asynchronism could be behind defective quality control in old organisms remain to be elucidated
  • Keywords: aging, chaperones,, Protein Homeostasis, cancer