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28 juny 2022 @ 12:00 - 14:00

Proteostasis of Aging and Stem Cells

Speaker: David Vilchez, PhD – Professor, CECAD Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases, Medical Faculty, University of Cologne, Germany.

“While it has long been noted that genome stability is a central function required for survival of stem cells, the role of proteostasis has not been explored. With the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells can destroy the resulting lineage of cells and possibly accelerate the aging process. Furthermore, the retention of damaged proteins by the stem cell could result in diminished stem cell function and premature aging. Therefore, a firm understanding of how stem cells maintain their proteostasis is of central importance. Because experiments with mammalian embryonic stem cells have clearly demonstrated their capacity to replicate continuously in the absence of senescence, we hypothesize that these cells could provide a novel paradigm to study the regulation of proteostasis and its demise in aging. We have recently described that human embryonic stem cells (hESCs) exhibit high proteasome activity compared to their differentiated counterparts. This enhanced proteasome activity is necessary for hESC function. Furthermore, we have uncovered that PSMD11/rpn-6, a key proteasomal subunit, is required for this activity and its mode of regulation and conservation in the aging process of the invertebrate C. elegans. Our findings established RPN-6 as a potent regulator of proteasome activity that alleviates the deleterious effects associated with aberrant protein aggregation, providing a powerful candidate to correct proteostatic deficiencies in disorders such as HD. Moreover, our results in C. elegans led us to find that FOXO4, a transcription factor associated with longevity, regulates proteasome activity in hESCs and is necessary for hESCs differentiation into neural cells. Therefore, our results established a novel regulation of proteostasis in hESCs that links longevity and stress resistance in invertebrates with hESC function and identity”.

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Data:
28 juny 2022
Hora:
12:00 - 14:00
Lloc web:
https://www.irbbarcelona.org/ca/events/proteostasis-aging-and-stem-cells

Organitzador

IRB Barcelona – Institut de Recerca Biomedica
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