Dec. 5: Thorsten Hoppe presents on proteostasis in aging as part of our "BIOLOGIES" OF AGING? Series

On Monday, December 5, 2016, visiting scientist Thorsten Hoppe will give a talk in a joint seminar with the Department of Genetics & Development. This seminar is part of our "BIOLOGIES" OF AGING? Series, launched early in 2016.  If you wish to attend, RSVPs are requested:


Monday, December 5, 2016, 12:30 pm 
Hammer Health Sciences Building, 701 W. 168th Street, Room 301

Presented by the Columbia Aging Center and the Department of Genetics and Development, this joint seminar features visiting scientist THORSTEN HOPPE, Principal Investigator at the Institute for Genetics and CECAD Research Center, University of Cologne.

ABSTRACT: Protein homeostasis (proteostasis) is supported by cellular quality control networks that govern protein synthesis, folding, and degradation. The progressive decline of proteostasis is a hallmark of aging and contributes to protein aggregation diseases. However, mechanistic principles coordinating proteostasis imbalance and life expectancy are not well understood. Here Hoppe and his co-authors report that proteostasis and longevity are strictly interrelated by the conserved quality control ubiquitin ligase CHIP. In cooperation with chaperone partners, CHIP ubiquitylates damaged polypeptides, which accumulate especially under proteotoxic stress. They show that in Caenorhabditis elegans and Drosophila melanogaster CHIP deficiency leads to increased levels of the conserved DAF-2/insulin receptor resulting in reduced lifespan and premature aging of the animals. The membrane bound insulin receptor regulates the insulin/IGF-1 signalling (IIS) pathway and thereby limits lifespan and stress responses.  Intriguingly, they identify the insulin receptor as a direct target of CHIP, which mediates receptor monoubiquitylation and endocytic turnover. Upon proteotoxic stress and during aging, however, CHIP activity is switched towards disposal of misfolded proteins, reducing its capacity to degrade the insulin receptor and support longevity. Thus, the study indicates a reciprocal balance between proteostasis and lifespan regulation through chaperone-assisted proteolysis, providing an evolutionarily conserved concept for understanding the impact of proteome imbalance on aging.