Identification of Age-Related Hallmarks of Amyotrophic Lateral Sclerosis as a Basis for the Search for New Disease Modifiers – AGED.ALS

AGED.ALS is a research project dedicated to the identification of age-related mechanisms of amyotrophic lateral sclerosis (ALS)—the most common motor neuron disease, leading to progressive paralysis and premature death. In an aging society, where neurodegenerative diseases pose an increasing health challenge, ALS remains an incurable condition, and aging is one of its key risk factors.

The aim of the project is to develop and characterize innovative human ALS models that enable the study of molecular mechanisms of the disease in the context of aging. Unlike classical models based on induced pluripotent stem cells (iPSCs), the project employs direct reprogramming of fibroblasts from ALS patients into motor neurons while preserving features of cellular aging. This approach allows for a more faithful recapitulation of late stages of the disease and enables investigation of the effects of mutations in key ALS-associated genes such as C9orf72, SOD1, TARDBP, and FUS.

Following validation of the new models, advanced proteomic analyses will be conducted to identify age-dependent signatures characteristic of ALS as well as potential disease modifiers. Selected factors will undergo further functional validation, and the research will be extended to include analysis of the role of astrocytes in the development of neuronal pathology. The AGED.ALS project aims to establish a unique research platform and to provide knowledge that may contribute to the development of new therapeutic strategies for ALS patients.