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

Area of Science:

• Cell Biology
• Gerontology
• Immunology

Background:

• Centenarians, individuals aged 100 years or more, often exhibit remarkable resilience to age-related diseases.
• Understanding the cellular mechanisms underlying exceptional longevity is crucial for developing interventions to promote healthy aging.
• Epstein-Barr virus (EBV)-stabilized lymphoid cell lines provide a model to study cellular characteristics associated with extreme age.

Purpose of the Study:

• To investigate the survival features of lymphoid B cells from centenarians compared to adult controls.
• To identify cellular mechanisms, including apoptosis resistance and phagocytic activity, contributing to the survival of cells from centenarians.
• To explore the molecular pathways and genetic factors associated with the observed survival phenotype.

Main Methods:

• Analysis of Epstein-Barr virus (EBV)-stabilized lymphoid cell lines from adult and centenarian subjects.
• Assessment of apoptosis induction resistance and lysosomal compartment development.
• Observation of cellular engulfment (phagic) behavior, including the effects of nutrient deprivation and autophagy modulators.
• Transcriptomic analysis to identify key genes and pathways involved in the survival phenotype.

Main Results:

• Lymphoid B cells from centenarians demonstrated significantly higher resistance to apoptosis induction compared to adult cells.
• Centenarian cells possessed a more developed lysosomal compartment and exhibited the ability to engulf and digest other cells (phagic behavior).
• This phagic behavior was enhanced by nutrient deprivation but unaffected by autophagy-modulating drugs (rapamycin and 3-methyladenine).
• Transcriptomic analysis revealed the involvement of aspartyl proteases, cell surface molecules (integrins, cadherins), cytoskeletal components, and Wnt signaling pathways.

Conclusions:

• Lymphoid B cells from centenarians possess distinct survival advantages, including apoptosis resistance and a unique phagic capability.
• The observed phagic behavior, independent of canonical autophagy pathways, may represent a significant survival determinant in centenarian cells.
• Molecular factors such as aspartyl proteases, specific cell surface molecules, and cytoskeletal remodeling via Wnt signaling likely contribute to this exceptional survival phenotype.