When cells divide, they must first replicate all of their genetic material. DNA replication is a very tightly controlled process; the double helix must be unwound, and the many enzymes involved must be coordinated to ensure that every nucleotide in each of our 46 chromosomes is copied exactly and only once. The system generally works pretty well, but the DNA replication machinery has a hard time with the ends of chromosomes, called telomeres.

Now, researchers have found that caffeine makes it more difficult for cells to copy the ends of their chromosomes. But that may be OK, since they also found that booze has the opposite effect.

Telomeres protect the ends of chromosome. Embryonic cells have a special enzyme, telomerase, that lengthens telomeres; after the cells specialize, however, they stop expressing telomerase. From there on, telomeres get shorter with each cell division since they are so difficult to replicate. Once telomeres reach a critically short length, the cell stops dividing altogether. Shorter telomeres are thus a hallmark of aging. Tumor cells start re-expressing telomerase, and their lengthened telomeres are one factor that allows them to divide indefinitely.

Psychological stress and poor socioeconomic status have been linked to shortened telomeres. (Remember: longer telomeres = cancer, shorter telomeres = age.) However, it has not yet been determined if these stresses actually cause a change in telomere length, and if so, how that might occur; it's possible that they simply accelerate the normal trend of aging.

To explore the effects of stress on telomere length, a group at Tel Aviv University turned to yeast, a simpler organism that also maintains telomeres. To find any molecular mechanisms involved in changing telomere length, they grew yeast in the presence of thirteen different environmental stresses, measured the lengths of their telomeres, and then analyzed their gene expression profiles. They found that caffeine (and high temperatures) shorten telomeres, and alcohol (and acetic acid) lengthen them. Oxidative stress had no effect.

At least six percent of yeast genes—some 400 genes—are involved in regulating telomere length. To home in on which genes might be important in these stress responses, the researchers looked at mutants that showed atypical stress responses—yeast strains with telomeres that did not get shorter when they were exposed coffee (the yeast strains, not the researchers). The most prominent of these genes was Rif-1, a negative regulator of telomerase. They found that exposure to ethanol (and isopropanol, and methanol) reduced the recruitment of Rif1 to telomeres. About ten other genes were also identified as playing roles.

Some telomeres are too long, and some are too short. Perhaps striking the right balance of caffeine and alcohol is the key to keeping them just right—as if you needed an excuse to have another hot toddy.

PLoS Genetics, 2013. DOI: 10.1371/journal.pgen.1003721 (About DOIs).