title: Role of Carbonyl Modifications on Aging-Associated Protein Aggregation.
abstract: Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.|Department of Chemistry, University of Bologna, Via Selmi 2, 40126, Bologna, Italy.
authors.forename: Maya
authors.initials: M
authors.lastname: Tanase
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Urbanska
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zolla
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Clement
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.
authors.forename: Liling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.
authors.forename: Kateryna
authors.initials: K
authors.lastname: Morozova
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Follo
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Goldberg
authors.affiliation: Department of Chemistry, University of Bologna, Via Selmi 2, 40126, Bologna, Italy.|by Flow srl, Via Fani 11/b, 40127 Bologna, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Roda
authors.affiliation: Department of Chemistry, University of Bologna, Via Selmi 2, 40126, Bologna, Italy.|by Flow srl, Via Fani 11/b, 40127 Bologna, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Reschiglian
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.|Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D005260:Female; D051379:Mice; D018384:Oxidative Stress; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D050050:Protein Carbonylation; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D066329:Protein Aggregates; D011506:Proteins; D017382:Reactive Oxygen Species