Organ- and tissue-specific alterations in the anti-apoptotic protein Bcl-2 in CD1 female mice of different ages.

The anti-apoptotic protein Bcl-2, which also has cytoprotective and antioxidant functions might be one of the crucial factors that altogether, establish how a cell may deal with stress and damage, contributing to longevity. Among the controversial issues to understand Bcl-2 functions in vivo, is to establish its content and variation in tissues during an organismal lifespan. In this work we analyzed the changes of Bcl-2 levels in lung, liver, heart, kidney, spleen and brain homogenates obtained from CD1 mice throughout their lifespan (newborn to 24 months). A tendency of increment was observed in all the organs analyzed, except brain where Bcl-2 was not detected. Bcl-2 over-expression during aging could be interpreted as a protective mechanism preventing cell death, despite the overall accumulated cell damage.

Bcl-2 protects against oxidative stress while inducing premature senescence.

Replicative senescence is a cellular response to stress that has been postulated to serve as a tumor suppression mechanism and a contributor to aging. Numerous experimental studies have demonstrated that an apparently identical senescent state can also be prematurely induced in vitro in different cell types following sublethal oxidative stress stimuli. The former suggests a molecular link between cell cycle regulation and cell survival that could involve regulatory proteins such as Bcl-2. There is strong evidence that, in addition to its well-known effects on apoptosis, Bcl-2 is involved in antioxidant protection and regulation of cell cycle progression. The aim of this work was to determine if the protection against oxidative stress mediated by Bcl-2 could prevent or delay oxidative stress-induced senescence. Using a retroviral infection system, Bcl-2 was overexpressed in primary, nonembryonic mice fibroblasts obtained from lungs derived from 2-month-old CD1 mice. Fibroblasts overexpressing Bcl-2 were exposed to 75 microM H2O2 for 2 h to induce SIPS. The rate of proliferation and the increment of senescent cells were then determined. Our results indicate that overexpression of Bcl-2 protected primary fibroblasts against oxidative stress-mediated reduction in cell proliferation, but did not prevent premature senescence.