Professors Dorothee Dormann and Edward Lemke of Johannes Gutenberg University Mainz (JGU), who also serve as adjunct directors at the Institute of Molecular Biology (IMB) in Mainz, suggest in a recent article published in Nature Cell Biology that measuring protein clumps in our cells could offer a novel approach to assessing our risk of age-related diseases.
As we age, alterations occur in the DNA and proteins comprising our bodies, leading to a decline in bodily functions and an increased susceptibility to age-related ailments like cardiovascular disease, cancer, and Alzheimer’s disease. A significant change involves the occasional misfolding and aggregation of proteins within our cells, resulting in the formation of clusters known as amyloids. While protein misfolding and aggregation can affect any protein, a specific set known as intrinsically disordered proteins (IDPs) are particularly prone to forming amyloids. IDPs, constituting roughly 30 percent of cellular proteins, lack a fixed structure and exhibit flexibility and dynamism akin to strands of cooked spaghetti.
Although the precise molecular mechanisms remain subject to debate, it’s understood that aggregates derived from IDPs tend to accumulate in long-lived cells such as neurons and muscle cells as we age. Furthermore, they can instigate various age-related disorders, particularly neurodegenerative conditions like Alzheimer’s and Parkinson’s disease. Thus, the presence of numerous aggregates within a cell might serve as an indicator of cellular health or predict the likelihood of developing age-related diseases. In their recent publication, Dormann and Lemke propose leveraging IDP aggregation as a biological “clock” for gauging an individual’s health and age.
The development of a protein aggregation clock into a sensitive diagnostic tool could prove immensely beneficial. Primarily, it could aid physicians in diagnosing age-related diseases at nascent stages or identifying individuals at elevated risk of disease onset as they age, facilitating early preventive interventions. Additionally, researchers could employ it to evaluate the efficacy of novel experimental therapies aimed at mitigating protein aggregation, thereby stalling or preventing age-related ailments.
“In practice, a routine diagnostic test remains distant, and enhancing our understanding of the underlying mechanisms governing IDP aggregation is crucial,” remarked Dormann.
While various “clocks” exist to gauge aging and health, most rely on nucleic acids like DNA. Dormann and Lemke posit that a protein-based biological clock would complement these existing methods effectively, given the abundance and indispensability of proteins in cellular functions. Through the adoption of such a protein aggregation clock, they envision a step forward in facilitating healthy aging and averting age-related diseases among individuals.
Dormann and Lemke’s research contributes to the Center for Healthy Ageing (CHA), a collaborative initiative launched in 2021. The CHA endeavors to unite scientists engaged in both basic and clinical research across Mainz, focusing on aging and age-related diseases, with the aim of promoting healthy aging and devising treatments to prevent or cure such ailments.
