Final Report Summary - PROTEODYNAMICS (Global Dynamics of Proteolytic Quality Control Networks in Stress Response and Aging)
The PROTEODYNAMICS project aimed to unravel the mechanisms through which the proteome is maintained during stress and aging. We were interested in how response mechanisms to proteotoxic conditions accelerate the aging process and age-related protein aggregation in Alzheimer’s and Parkinson’s patients. In the PROTEODYNAMICS project we have employed the powerful genetic model of Caenorhabditis elegans as multicellular organism to study how different protein degradation pathways are mechanistically coordinated during animal development and aging. We have uncovered a conserved coordination between longevity assurance mechanisms that maintain tissue-specific functions and the response to proteostasis defects accumulation with age. We have identified novel non-cell-autonomous signaling pathways that allow cross communication between different tissues to adapt to age-related increase of protein damage. Our work contributed to one of the first publications on ubiquitin-dependent regulation of the aging process and showed how ubiquitin-dependent degradation of the conserved insulin receptor affects the coordination between organismal proteostasis and longevity in worms, flies, and human cells. Moreover, we addressed how the smell of food sensed via a single pair of olfactory neurons affects physiology and aging. Especially the proposed mechanism of food perception will stimulate further research on neuroendocrine brain-to-gut communication and therapeutic interventions to improve proteostasis and organismal health via the sense of smell, with potential implications for obesity, diabetes and aging.