Does proteostasis get lost in translation? Implications for protein aggregation across the lifespan

Area of Science:

• Biochemistry
• Molecular Biology
• Gerontology

Background:

• Protein aggregation is implicated in various diseases, including neurodegenerative disorders and diabetes.
• While protein aggregation is observed in healthy aging, its biological significance is unclear.
• Proteome homeostasis (proteostasis) relies on balanced protein synthesis, accurate folding, and degradation of damaged proteins.

Purpose of the Study:

• To review literature on age-related decline in proteostasis.
• To highlight the need for an integrated view of protein synthesis and quality control in aging.
• To understand proteome alterations in aging and age-related diseases.

Main Methods:

• Literature review of recent studies on age-related proteostasis.
• Analysis of hypotheses linking protein synthesis dysregulation to protein aggregation.
• Examination of proteostasis network (PN) pathways in aging.

Main Results:

• Age-related protein aggregation may stem from altered protein synthesis and proteostasis network (PN) dysregulation.
• Hypothesized causes include reduced protein synthesis accuracy and translation fidelity.
• Controversial data exists, and mechanisms for widespread aggregation require further elucidation.

Conclusions:

• Understanding age-related protein aggregation requires integrating protein synthesis rate, fidelity, and quality control.
• Further research is crucial to elucidate the mechanisms and biological relevance of protein aggregation during aging.
• This knowledge is vital for understanding aging and developing strategies for age-related diseases.