Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation
Δημιουργός/Συγγραφέας:	Kelmer Sacramento, Erika Kirkpatrick, Joanna M Mazzetto, Mariateresa Baumgart, Mario Bartolome, Aleksandar Di Sanzo, Simone Caterino, Cinzia Sanguanini, Michele Papaevgeniou, Nikoletta Lefaki, Maria Childs, Dorothee Bagnoli, Sara Terzibasi Tozzini, Eva Di Fraia, Domenico Romanov, Natalie Sudmant, Peter H Huber, Wolfgang [EL] Χονδρογιάννη, Νίκη[EN] Chondrogianni, Niki Vendruscolo, Michele Cellerino, Alessandro Ori, Alessandro
Ημερομηνία:	2020-06
Γλώσσα:	Αγγλικά
ISSN:	1744-4292 1744-4292
DOI:	10.15252/msb.20209596
Άλλο:	32558274
Περίληψη:	A progressive loss of protein homeostasis is characteristic of aging and a driver of neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain aging in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics and proteomics. We detected a progressive reduction in the correlation between protein and mRNA, mainly due to post-transcriptional mechanisms that account for over 40% of the age-regulated proteins. These changes cause a progressive loss of stoichiometry in several protein complexes, including ribosomes, which show impaired assembly/disassembly and are enriched in protein aggregates in old brains. Mechanistically, we show that reduction of proteasome activity is an early event during brain aging and is sufficient to induce proteomic signatures of aging and loss of stoichiometry in vivo. Using longitudinal transcriptomic data, we show that the magnitude of early life decline in proteasome levels is a major risk factor for mortality. Our work defines causative events in the aging process that can be targeted to prevent loss of protein homeostasis and delay the onset of age-related neurodegeneration.
Τίτλος πηγής δημοσίευσης:	Molecular systems biology
Τόμος/Κεφάλαιο:	16
Τεύχος:	6
Σελίδες:	e9596 |
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry [EL] Βιοπληροφορική[EN] Bioinformatics [EL] Κυτταρολογία[EN] Cytology
Λέξεις-Κλειδιά:	Lifespan Proteome Stoichiometry Transcriptome Aging Animals Biophysical Phenomena Brain Cyprinodontiformes Mice, Inbred C57BL Proteasome Endopeptidase Complex RNA, Messenger Reproducibility of Results Ribosomal Proteins Ribosomes Risk Factors Protein Aggregates
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.embopress.org/doi/full/10.15252/msb.20209596
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.embopress.org/journal/17444292
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο