Old Proteins in Man: A Field in its Infancy

Area of Science:

• Biochemistry
• Gerontology
• Immunology

Background:

• The human body contains numerous long-lived proteins (LLPs).
• Gradual degradation of LLPs contributes to aging and age-related disorders.
• Neurological diseases often manifest after middle age, suggesting a role for protein damage.

Purpose of the Study:

• To explore the contribution of long-lived protein degradation to human aging.
• To investigate the mechanisms of protein deterioration and their consequences.
• To understand the potential for autoimmune responses due to altered protein structures.

Main Methods:

• Analysis of protein degradation pathways.
• Identification of chemical modifications in aged proteins (racemization, truncation, deamidation, crosslinking).
• Investigation of structural and functional changes in deteriorating proteins.

Main Results:

• Long-lived proteins undergo spontaneous breakdown of amino acid residues.
• These degradation processes alter protein structure and function.
• Novel epitopes are formed on damaged proteins, potentially inducing autoimmunity.

Conclusions:

• Protein degradation is a significant factor in human aging.
• Altered proteins can lead to functional deficits and disease.
• The formation of new epitopes on damaged proteins may drive autoimmune reactions in aging.