Towards a Protein Aggregation Clock for Biological Age
There are many ways to construct a measure of biological age. Any form of complex data that varies over the course of aging will suffice. Machine learning can determine algorithmic combinations of measured values that correlate with age, and then one can assess the biological age of an individual by seeing where they fit into the established trend. Here, researchers advocate for the use of protein aggregate levels as the underlying data upon which to build a clock. Many different proteins can aggregate with advancing age, and tend to do so to a greater degree in later life, so this data could be used to build novel clocks with which to measure biological age.
As we age, the DNA and proteins that make up our bodies gradually undergo changes that cause our bodies to no longer work as well as before. This in turn makes us more prone to getting age-related diseases, such as cardiovascular disease, cancer, and Alzheimer's disease. One important change is that the proteins in our cells can sometimes become misfolded and clump together to form aggregates, so-called amyloids. Misfolding and aggregation can happen to any protein, but a specific group of proteins known as intrinsically disordered proteins (IDPs) are especially prone to forming amyloids. IDPs make up around 30 percent of the proteins in our cells and they are characterized by having no fixed structure. Instead, they are flexible and dynamic, flopping around like strands of cooked spaghetti.
While the molecular mechanisms are widely debated and an important aspect of basic research, scientists know that aggregates formed from IDPs tend to accumulate in many long-lived cells - such as neurons or muscle cells - as we age. Moreover, they can cause many age-related diseases, particularly neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Thus, having many aggregates in a cell could be an indicator of how unhealthy the cell is or if a person is likely to develop an age-related disease soon. In a recently published article, researchers propose that IDP aggregation could be used as a biological "clock" to measure a person's health and age.
"In practice, we are still far away from a routine diagnostic test, and it is important that we improve our understanding of the fundamental mechanisms leading to IDP aggregation. However, we want to stimulate thinking and research in the direction of studying protein aggregates to measure biological ageing processes. We are optimistic that in the future we will be able to overcome the current challenges of reading a protein aggregation clock through more research on IDP dynamics and making further technological developments."