Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans
Δημιουργός/Συγγραφέας:	[EL] Χονδρογιάννη, Νίκη[EN] Chondrogianni, Niki Georgila K. Kourtis N. Tavernarakis N. [EL] Γκόνος, Ευστάθιος[EN] Gonos, Efstathios S.
Εκδότης:	FASEB
Ημερομηνία:	2015
Γλώσσα:	Αγγλικά
ISSN:	0892-6638
DOI:	10.1096/fj.14-252189
Άλλο:	PubMed ID: 25395451
Περίληψη:	Protein homeostasis (proteostasis) is one of the nodal points that need to be preserved to retain physiologic cellular/organismal balance. The ubiquitin-proteasome system (UPS) is responsible for the removal of both normal and damaged proteins, with the proteasome being the downstream effector. The proteasome is the major cellular protease with progressive impairment of function during aging and senescence. Despite the documented age-retarding properties of proteasome activation in various cellular models, simultaneous enhancement of the 20S core proteasome content, assembly, and function have never been reported in any multicellular organism. Consequently, the possible effects of the core proteasome modulation on organismal life span are elusive. In this study, we have achieved activation of the 20S proteasome at organismal level. We demonstrate enhancement of proteasome levels, assembly, and activity in the nematode Caenorhabditis elegans, resulting in life span extension and increased resistance to stress. We also provide evidence that the observed life span extension is dependent on the transcriptional activity of Dauer formation abnormal/Forkhead box class O (DAF-16/FOXO), skinhead-1 (SKN-1), and heat shock factor-1 (HSF-1) factors through regulation of downstream longevity genes. We further show that the reported beneficial effects are not ubiquitous but they are dependent on the genetic context. Finally, we provide evidence that proteasome core activation might be a potential strategy to minimize protein homeostasis deficiencies underlying aggregation-related diseases, such as Alzheimer's disease (AD) or Huntington's disease (HD). In summary, this is the first report demonstrating that 20S core proteasome up-regulation in terms of both content and activity is feasible in a multicellular eukaryotic organism and that in turn this modulation promotes extension of organismal health span and life span.
Τίτλος πηγής δημοσίευσης:	FASEB Journal
Τόμος/Κεφάλαιο:	29
Τεύχος:	2
Σελίδες:	611-622
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	Aging Daf-16 Longevity Proteostasis
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© FASEB.
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Green
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο