Professors Dorothee Dormann and Edward Lemke from Johannes Gutenberg University Mainz (JGU), who also serve as adjunct directors at the Institute of Molecular Biology (IMB) in Mainz, have introduced the idea of a “protein aggregation clock” as a novel method for assessing ageing and disease risk. They discussed this concept in a new perspective article they published in Nature Cell Biology.
As humans age, the DNA and proteins that constitute our bodies undergo various changes, diminishing our bodily functions and increasing susceptibility to age-related diseases such as cardiovascular diseases, cancer, and Alzheimer’s disease. A significant change is the misfolding and subsequent aggregation of proteins into amyloids within our cells. These protein aggregates, mainly formed from a category of proteins known as intrinsically disordered proteins (IDPs), which lack a fixed structure and account for about 30 per cent of cellular proteins, are a hallmark of ageing cells. These proteins are more flexible, resembling strands of cooked spaghetti, and are especially prone to form amyloids.
The accumulation of these aggregates, especially in long-lived cells like neurons or muscle cells, is a well-known phenomenon as we age and is associated with numerous age-related diseases, including neurodegenerative conditions like Alzheimer’s and Parkinson’s disease. Consequently, multiple aggregates could indicate cellular health and the likelihood of developing age-related diseases.
In their article, Dormann and Lemke suggest that tracking IDP aggregation might serve as a biological “clock” to gauge an individual’s health and biological age. The potential development of this concept into a sensitive diagnostic tool is a source of optimism. It could enable early diagnosis of age-related diseases and identify individuals at risk before they show symptoms, thereby allowing for preventative interventions. Additionally, it could be employed to evaluate the efficacy of new treatments aimed at reducing protein aggregation, thus helping to delay or prevent age-related diseases.
However, the realization of a routine diagnostic test based on protein aggregation is still a distant goal. Dormann emphasized the necessity of enhancing our understanding of the fundamental mechanisms behind IDP aggregation. Meanwhile, Lemke expressed hope that further research into IDP dynamics and technological advancements could eventually make reading a protein aggregation clock a reality.
While various biological “clocks” based on nucleic acids like DNA already exist, a protein-based clock could provide a valuable complement to these tools. Proteins are pivotal in all cellular functions and are abundantly present in cells. By advancing the protein aggregation clock, Dormann and Lemke aim to make a significant contribution to the field of gerontology, inspiring hope for the development of strategies for healthy ageing and the prevention of age-related diseases.
More information: Dorothee Dormann et al, Adding intrinsically disordered proteins to biological ageing clocks, Nature Cell Biology. DOI: 10.1038/s41556-024-01423-w
Journal information: Nature Cell Biology Provided by Johannes Gutenberg University of Mainz
