title: Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing.
abstract: The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular senescence. Organismal ageing in mammals is associated with accumulation of markers of cellular senescence and DDR persistence at telomeres. Since the vast majority of the cells in mammals are non-proliferating, how do they age? Are telomeres involved? Also oncogene activation causes cellular senescence due to altered DNA replication and DDR activation in particular at the telomeres. Is there a common mechanism shared among apparently distinct types of cellular senescence? And what is the role of telomeric DNA damage?
authors.affiliation: IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan 20139, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossiello
authors.affiliation: Department of Microbiology and Molecular Genetics, New Jersey Medical School - Cancer Center, Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ 07103, USA.
authors.forename: Utz
authors.initials: U
authors.lastname: Herbig
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan 20126, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Longhese
authors.affiliation: IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan 20139, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Fumagalli
authors.affiliation: IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan 20139, Italy; Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia 27100, Italy. Electronic address: fabrizio.dadda@ifom.eu.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: d'Adda di Fagagna
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D015398:Signal Transduction / Q000235:genetics*; D016615:Telomere / Q000235:genetics
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