Life expectancy has risen remarkably and the number of older people will continue to increase. Aging is a major risk factor for neurodegenerative diseases that involve protein aggregation, such as amyotrophic lateral sclerosis (ALS), Huntington’s (HD), Parkinson’s and Alzheimer’s. We have discovered that aging induces a rewiring of the ubiquitinated proteome, whereby hundreds of proteins undergo changes in ubiquitin modifications. Given the central role of ubiquitination in cell function, a functional study of these alterations can lead to novel modifiers of aging and disease. Together, our approach that combines state-of-the-art proteomics, human iPSC-disease modelling and genetics in the model organism C. elegans can provide insights into converging strategies for preventing and/or treating different age-related neurodegenerative disorders.
Aging causes a progressive loss of physiological integrity, which can trigger the development of multiple pathologies that remain incurable. As such, our ever-aging society presents a challenge from the increasing prevalence of age-related diseases. Our innovative approach will define targets to slow down aging and prevent age-related neurodegenerative diseases. Thus, our project can have important implications for multi-disease prevention and be of enormous benefit for our ever-aging society.
Seda Koyuncu, Hyun Ju Lee, Will Zhang
Hafiza Alirzayeva, Saygin Bilican, Franziska Hommen, Angela Joy Johns, Markus Wehrmann
Melissa Chmara, Nassima Salarzai