Old Proteins in Man: A Field in its Infancy. Issue 8 (August 2016)

• Record Type: Journal Article
• Authors: Truscott, Roger J.W.; Schey, Kevin L.; Friedrich, Michael G.
• Is Part Of: Trends in biochemical sciences. Volume 41:Issue 8(2016)
• Page Start: 654
• Page End: 664
• Publication Date: 2016-08
• Subjects: protein aging -- post-translational modification -- racemization -- age-related disease.; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2016.06.004
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : It has only recently been appreciated that the human body contains many long-lived proteins (LLPs). Their gradual degradation over time contributes to human aging and probably also to a range of age-related disorders. Indeed, the role of progressive damage of proteins in aging may be indicated by the fact that many neurological diseases do not appear until after middle age. A major factor responsible for the deterioration of old proteins is the spontaneous breakdown of susceptible amino acid residues resulting in racemization, truncation, deamidation, and crosslinking. When proteins decompose in this way, their structures and functions may be altered and novel epitopes can be formed that can induce an autoimmune response. Trends: LLPs are present throughout the body. Over time, LLPs degrade as a result of spontaneous processes and modification by reactive metabolites. When an LLP breaks down, it generates new structures that the body can recognize as foreign, and may therefore mount an immune response towards the modified as well as the parent protein. These crucial aspects of human aging and age-related disease are very difficult to study using the traditional experimental approaches (e.g., animal models) and have been largely ignored.