title: Changes in autophagy, proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells.
abstract: A sharp definition of what a senescent cell is still lacking since we do not have in depth understanding of mechanisms that induce cellular senescence. In addition, senescent cells are heterogeneous, in that not all of them express the same genes and present the same phenotype. To further clarify the classification of senescent cells, hints may be derived by the study of cellular metabolism, autophagy and proteasome activity. In this scenario, we decided to study these biological features in senescence of Mesenchymal Stromal Cells (MSC). These cells contain a subpopulation of stem cells that are able to differentiate in mesodermal derivatives (adipocytes, chondrocytes, osteocytes). In addition, they can also contribute to the homeostatic maintenance of many organs, hence, their senescence could be very deleterious for human body functions. We induced MSC senescence by oxidative stress, doxorubicin treatment, X-ray irradiation and replicative exhaustion. The first three are considered inducers of acute senescence while extensive proliferation triggers replicative senescence also named as chronic senescence. In all conditions, but replicative and high IR dose senescence, we detected a reduction of the autophagic flux, while proteasome activity was impaired in peroxide-treated and irradiated cells. Differences were observed also in metabolic status. In general, all senescent cells evidenced metabolic inflexibility and prefer to use glucose as energy fuel. Irradiated cells with low dose of X-ray and replicative senescent cells show a residual capacity to use fatty acids and glutamine as alternative fuels, respectively. Our study may be useful to discriminate among different senescent phenotypes.
authors.affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Capasso
authors.affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Alessio
authors.affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Squillaro
authors.affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Bernardo
authors.affiliation: Institute of Bioscience and Bioresources, CNR, Naples, Italy.|Department of Clinical and Experimental Medicine and Surgery, Division of Neurology, Second University of Naples, Naples, Italy.
authors.forename: Mariarosa A
authors.initials: MA
authors.lastname: Melone
authors.affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Cipollaro
authors.affiliation: Institute of Bioscience and Bioresources, CNR, Naples, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Peluso
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA.|Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.|Institute of Bioscience and Bioresources, CNR, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D015153:Blotting, Western; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002648:Child; D004317:Doxorubicin / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000528:radiation effects; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000528:radiation effects; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014965:X-Rays
chemical_list: D000903:Antibiotics, Antineoplastic; D005227:Fatty Acids; D005973:Glutamine; D004317:Doxorubicin; D046988:Proteasome Endopeptidase Complex; D005947:Glucose
keywords: Gerotarget; autophagy; mesenchymal stem cells; metabolism; proteasome; senescence