title: Survival features of EBV-stabilized cells from centenarians: morpho-functional and transcriptomic analyses.
abstract: In the present work, we analyzed the survival features of six different Epstein-Barr virus (EBV)-stabilized lymphoid cell lines obtained from adult subjects and from subjects of more than 95 years. For the first, we found that lymphoid B cells from centenarians were more resistant to apoptosis induction and displayed a more developed lysosomal compartment, the most critical component of phagic machinery, in comparison with lymphoid B cells from adult subjects. In addition, cells from centenarians were capable of engulfing and digesting other cells, i.e., their siblings (even entire cells), whereas lymphoid cells from "control samples", i.e., from adults, did not. This behavior was improved by nutrient deprivation but, strikingly, it was unaffected by the autophagy-modulating drug, rapamycin, an autophagy inducer, and 3-methyladenine, an autophagy inhibitor. Transcriptomic analyses indicated that: (1) aspartyl proteases, (2) cell surface molecules such as integrins and cadherins, and (3) some components of cytoskeletal network could contribute to establish this survival phenotype. Also, Kyoto Encyclopedia of Genes and Genomes pathways such as Wnt signaling pathway, an essential contributor to cell migration and actin cytoskeleton remodeling, appeared as prominent. Although we cannot rule out the possibility that EBV-immortalization could play a role, since we observed this phagic behavior in cells from centenarians but not in those from adults, we hypothesize that it may represent an important survival determinant in cells from centenarians.
authors: Department of Drug Therapy and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors: Paola
authors: P
authors: Matarrese
authors: Antonella
authors: A
authors: Tinari
authors: Barbara
authors: B
authors: Ascione
authors: Lucrezia
authors: L
authors: Gambardella
authors: Daniel
authors: D
authors: Remondini
authors: Stefano
authors: S
authors: Salvioli
authors: Elena
authors: E
authors: Tenedini
authors: Enrico
authors: E
authors: Tagliafico
authors: Claudio
authors: C
authors: Franceschi
authors: Walter
authors: W
authors: Malorni
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics; D000328:Adult; D000369:Aged, 80 and over / Q000502:physiology*; D057055:Aspartic Acid Proteases / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D015820:Cadherins / Q000235:genetics; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics*; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics; D010641:Phenotype
chemical_list: D015820:Cadherins; D016023:Integrins; D057055:Aspartic Acid Proteases