Telomeres protect the chromosome ends from degradation and play crucial roles in cellular aging and disease. Recent studies have additionally found a correlation between psychological stress, telomere length, and health outcome in humans. However, studies have not yet explored the causal relationship between stress and telomere length, or the molecular mechanisms underlying that relationship. Using yeast as a model organism, we show that stresses may have very different outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high temperatures shorten telomeres. Additional treatments, such as oxidative stress, show no effect. By combining genome-wide expression measurements with a systematic genetic screen, we identify the Rap1/Rif1 pathway as the central mediator of the telomeric response to environmental signals. These results demonstrate that telomere length can be manipulated, and that a carefully regulated homeostasis may become markedly deregulated in opposing directions in response to different environmental cues.

No abstract

The lack of responsiveness to self and non-self Ags is normally maintained by multiple mechanisms, including the suppressive activities of several T cell subsets. In this study, we show that CD8+ T cells from both adult peripheral blood and umbilical cord blood mononuclear cells constitutively expressing HLA-DR represent a natural human CD8+ regulatory T cell subset. Their suppressive effect appears to be cell-to-cell contact dependent and may involve CTLA-4 signaling between neighboring T cells. These regulatory T cells can be expanded in vitro and exhibit a suppressive capacity similar to that observed in ex vivo CD8+HLA-DR+ T cells. The high frequency of CD8+HLA-DR+ T cells that we detected in patients with non–small cell lung cancer deserves further work to confirm their putative suppressor effect within the tumor.