PRR Project

Summary

Scientific progress over the past three decades has revolutionized our understanding of aging, revealing that its biology can be approached much like that of typical human biology or pathologies. The notion of aging as an insurmountably complex and inevitable aspect of life, resistant to study or yielding progress in health outcomes, has vanished from scientific discourse and textbooks. Instead, various researchers have unveiled methods to identify and quantify molecular damage associated with aging, delineated hallmarks of aging, elucidated molecular mechanisms and gene networks involved in aging, and underscored aging´s pivotal role as the major driver of age-related diseases. Sophisticated assays, along with cellular and animal models, have been devised to study aging processes and various anti-aging drugs have been discovered, with some progressing through clinical trials. Crucially, the concept of biological aging and methods for its quantification have facilitated investigations into the effects of gene manipulation, drug interventions, nutritional influences, and environmental factors, fostering a multidisciplinary approaches to unravelling aging biology.Studies in both humans and animal models support the idea that age-related cognitive decline is more likely associated with changes in neuronal/synaptic transmission than with neuronal loss. This distinction is a key difference between normal aging and neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, which are characterized by a significant decline in cell number. Additionally, aging is the major risk factor for neurodegeneration, leading to neuronal loss and cognitive decline.  Hence, the candidate is expected to investigate if the molecular basis of synaptic and neuronal loss in the aged and diseased brain is key to generating therapeutic interventions that could prevent the decline in cognition observed during aging and neurodegeneration, thereby increasing healthy lifespan. Therefore, the candidate should have strong expertise in synapse biology, neuronal trafficking, cell-adhesion proteins and proteomics.The research programme should be directed to understand the trafficking of neuronal proteins, a process that is significantly impaired with aging and is essential for protein delivery to the synapse. In particular, mechanisms leading to neuronal degeneration during pathological aging, including the molecular machinery responsible for cargo sorting in neuronal polarization; age-dependent changes in neuronal trafficking; polarization and neuronal communication should be the main focus of the new research group leader.