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Definition: When does the efficiency of protein refolding decline during aging?

Protein refolding is a crucial process in maintaining cellular function and homeostasis. It involves the restructuring of misfolded or denatured proteins into their native, functional conformation. However, as organisms age, the efficiency of protein refolding tends to decline, leading to the accumulation of misfolded or aggregated proteins.

Factors contributing to the decline in protein refolding efficiency during aging:

Decreased chaperone activity: Chaperones are proteins that assist in the refolding of misfolded proteins. With age, the expression and activity of chaperones may decline, impairing their ability to effectively refold proteins.

Increased oxidative stress: Aging is associated with an accumulation of reactive oxygen species (ROS) and oxidative damage. Oxidative stress can lead to protein misfolding and aggregation, overwhelming the cellular machinery responsible for refolding.

Impaired proteostasis network: The proteostasis network is a complex system involving chaperones, proteases, and other cellular components that work together to maintain protein homeostasis. During aging, this network can become dysregulated, compromising the efficiency of protein refolding.

Age-related changes in protein quality control mechanisms: Aging is accompanied by alterations in the ubiquitin-proteasome system and autophagy, which are responsible for the degradation of misfolded or aggregated proteins. Dysfunction in these mechanisms can lead to the accumulation of damaged proteins and further hinder protein refolding.

Genetic and epigenetic factors: Certain genetic variations or epigenetic modifications can influence the efficiency of protein refolding during aging. These factors can affect the expression or activity of chaperones, proteases, or other components involved in the refolding process.

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Understanding the decline in protein refolding efficiency during aging is crucial for unraveling the molecular mechanisms underlying age-related diseases, such as neurodegenerative disorders. By identifying strategies to enhance protein refolding capacity, it may be possible to mitigate the detrimental effects of protein misfolding and improve overall longevity and healthspan.

Keywords: protein, refolding, proteins, efficiency, decline, during, misfolded, chaperones, cellular