Bcl-xL as a Modulator of Senescence and Aging.

Autores de INCLIVA

• 

  Cristina Mas Bargues

  Autor

• 

  Consuelo Borras Blasco

  Autor

• 

  Jose Viña Ribes

  Autor

Grupos y Plataformas de I+D+i

• Grupo de Investigación en Envejecimiento Saludable

  

  Leading Researcher

  Consuelo Borras Blasco

• Grupo de investigación en envejecimiento y ejercicio físico

  

  Leading Researcher

  Jose Viña Ribes

Abstract

Many features of aging result from the incapacity of cells to adapt to stress conditions. When cells are overwhelmed by stress, they can undergo senescence to avoid unrestricted growth of damaged cells. Recent findings have proven that cellular senescence is more than that. A specific grade of senescence promotes embryo development, tissue remodeling and wound healing. However, constant stresses and a weakening immune system can lead to senescence chronicity with aging. The accumulation of senescent cells is directly related to tissue dysfunction and age-related pathologies. Centenarians, the most aged individuals, should accumulate senescent cells and suffer from their deleterious effects, however, they enjoy a compression of morbidity. We have shown that they overexpress B-cell lymphoma-extra large (Bcl-xL). Bcl-xL could avoid an excessive burden of senescent cells through the regulation of intrinsic apoptosis, mitochondrial bioenergetics and oxidative stress. On the other hand, Bcl-xL maintains a fully functional immune system that ensures an efficient clearance of senescent cells. Moreover, there is a paradox, as inhibitors of Bcl-xL have been employed as senolytic agents, which have been shown to protect from aging in animal models. In this review, we aim to discuss how Bcl-xL could modulate senescence-associated harmful effects in centenarians, protecting them from the burden of accumulation of senescent cells.

Keywords

• Bcl-xL; aging; apoptosis; centenarians; immunosenescence; senescence; senolytics