Could measuring protein clumps in our cells be a groundbreaking method to assess our risk for age-related diseases? Professors Dorothee Dormann and Edward Lemke of Johannes Gutenberg University Mainz (JGU), also adjunct directors at the Institute of Molecular Biology (IMB) in Mainz, propose the innovative concept of a "protein aggregation clock" to gauge aging and health. Their perspective article, recently published in Nature Cell Biology, opens new avenues in understanding how we age.

As we grow older, the DNA and proteins in our bodies undergo changes, impairing their function and making us more susceptible to age-related diseases like cardiovascular disease, cancer, and Alzheimer's. One crucial change involves proteins that become misfolded and clump together, forming aggregates known as amyloids. While misfolding and aggregation can occur in any protein, intrinsically disordered proteins (IDPs) are particularly prone to forming amyloids. These IDPs, making up about 30 percent of our cellular proteins, lack a fixed structure, behaving more like strands of cooked spaghetti.

Although the molecular mechanisms behind protein aggregation are still under investigation, scientists know that aggregates from IDPs accumulate in many long-lived cells, such as neurons and muscle cells, as we age. These aggregates are linked to numerous age-related diseases, especially neurodegenerative conditions like Alzheimer's and Parkinson's. Consequently, a high number of aggregates in a cell could indicate poor cell health or a higher likelihood of developing an age-related disease. Dormann and Lemke propose that IDP aggregation could serve as a biological "clock" to measure a person's health and age.

Developing a protein aggregation clock into a diagnostic tool could have significant benefits. Doctors could use it to diagnose age-related diseases early or identify individuals at higher risk before symptoms appear, allowing for preventive treatments. Scientists could also utilize it to evaluate the effectiveness of new treatments aimed at reducing protein aggregation and delaying or preventing age-related diseases.

"We are still far from a routine diagnostic test, but it's crucial to deepen our understanding of the fundamental mechanisms leading to IDP aggregation," said Dormann. "We hope to inspire further research into protein aggregates as a measure of biological aging," added Lemke. "We are optimistic that future advancements in IDP dynamics research and technology will overcome current challenges in reading a protein aggregation clock."

Current methods to measure aging and health primarily focus on nucleic acids like DNA. Dormann and Lemke believe a protein-based biological clock would complement these existing methods, given proteins' abundance and essential roles in cellular functions. They hope that such a clock will bring scientists and doctors closer to promoting healthy aging and preventing age-related diseases.

Dorothee Dormann and Edward Lemke's research contributes to the Center for Healthy Ageing (CHA), a virtual research center launched in 2021. The CHA unites scientists from various disciplines across Mainz to focus on aging and age-related diseases. Their findings aim to promote healthy aging and develop treatments to prevent or cure age-related diseases.