What is the Origin of Proteostasis Loss?

This term is central to cellular and molecular biology, combining "protein" and "homeostasis" to describe the essential process of protein quality control. Its clinical relevance has surged with the understanding that age-related diseases often involve protein aggregation. The concept highlights the critical need for robust cellular maintenance systems.

What is the Mechanism of Proteostasis Loss?

The mechanism involves the failure of key pathways like the ubiquitin-proteasome system and autophagy. As these systems become less efficient with age, damaged or misfolded proteins are not cleared effectively, leading to cellular stress and toxicity. Hormones and small molecules that activate stress response pathways, such as heat shock factors, can be utilized to enhance the cell's intrinsic capacity to restore proper protein folding and degradation kinetics.

Proteostasis Loss

Meaning

Proteostasis Loss describes the progressive failure of the cellular machinery responsible for maintaining protein homeostasis, which is the delicate balance between the synthesis, folding, trafficking, and degradation of proteins. This loss results in the accumulation of misfolded or aggregated proteins, overwhelming the cell’s quality control systems, and is a core hallmark of cellular aging and neurodegenerative diseases. The inability to properly manage the proteome compromises cellular function and ultimately leads to tissue and organ decline. Restoring proteostasis is a key objective in longevity science.