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Title: Widespread protein aggregation across the mouse lifespan
Author: Martins, Filipa
Francisco, Stephany
Sousa, Jéssica
Pereira, Cátia D.
Correia, Liliana
Camões, Fátima
Helguero, Luísa
Soares, Ana Raquel
Rebelo, Sandra
Keywords: Aging
Protein aggregation
Issue Date: Jun-2019
Abstract: Aging is characterized by a gradual decline in overall organismal fitness across the lifespan, and greatly enhances the risk for chronic diseases, as neuropathological disorders, diabetes, cancer and cardiovascular diseases. One of the hallmarks of aging is the loss of proteostasis, a regulated process responsible for maintaining the cellular proteome. When proteostasis is altered, proteome and proteostasis network disruptions occur, leading to accumulation of protein aggregates, characteristic of several age-related diseases. Previous work performed in Caenorhabditis elegans and zebrafish unveiled asymptomatic protein aggregation (ARPA), characterized by generalized increased accumulation of insoluble proteins through aging in healthy animals. We hypothesize that proteome imbalances occur with aging in mammals and they correlate with tissue aging and susceptibility for the development of age-related disease. The main goal of this work is to perform a global proteomic characterization of age-dependent protein aggregation in mice. C57BL/6 mice with different ages (6, 13, 18, 24 and 29 months) were used and the detergent-insoluble fractions isolated from total protein extracts of different tissues. Protein profiles were characterized by automated capillary electrophoresis separation using the LabChip GX. Our results suggest that proteome alterations occur during aging in mammals, and a tissue-specific insoluble protein signature across the lifespan is observed. For the cortex, the identification of the proteins more prone to aggregate during aging was performed by mass spectrometry and characterized to establish the functions and biological processes affected by ARPA. This will allow identifying novel aging biomarkers that may be relevant for disease onset and progression.
Peer review: no
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