Survival features of EBV-stabilized cells from centenarians: Morpho-functional and transcriptomic analyses

Paola Matarrese, Antonella Tinari, Barbara Ascione, Lucrezia Gambardella, Daniel Remondini, Stefano Salvioli, Elena Tenedini, Enrico Tagliafico, Claudio Franceschi, Walter Malorni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1341-1359
Number of pages19
JournalAge
Volume34
Issue number6
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Apoptosis
  • Autophagy
  • Cannibalism
  • Centenarians
  • Lymphoid cells
  • Transcriptomic analysis

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology
  • Medicine(all)

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    Matarrese, P., Tinari, A., Ascione, B., Gambardella, L., Remondini, D., Salvioli, S., Tenedini, E., Tagliafico, E., Franceschi, C., & Malorni, W. (2012). Survival features of EBV-stabilized cells from centenarians: Morpho-functional and transcriptomic analyses. Age, 34(6), 1341-1359. https://doi.org/10.1007/s11357-011-9307-4