Researchers at Stanford University School of Medicine have unearthed a connection between advancing age, systemic inflammation, cardiovascular disease and coffee consumption.

An extensive analysis of blood samples, survey data and medical and family histories obtained from more than 100 human participants has revealed a fundamental inflammatory mechanism associated with human aging and the chronic diseases that come with it.

The study indicates that metabolites, or breakdown products, of nucleic acids, which serve as building blocks for our genes, circulating in the blood can trigger the inflammatory process, which in turn can be a driver of cardiovascular disease and increased rates of mortality overall.

"More than 90 percent of all noncommunicable diseases of aging are associated with chronic inflammation," said David Furman, a consulting associate professor at the Stanford Institute for Immunity, Transplantation and Infection and lead author of the study published online this week in Nature Medicine.

As shown by more than 1,000 papers, chronic inflammation contributes to many cancers, Alzheimer's disease and other dementias, cardiovascular disease, osteoarthritis and even depression.

The multiyear study provides evidence that caffeine and its metabolites may counter the action of these circulating nucleic-acid metabolites, possibly explaining why coffee drinkers tend to live longer than abstainers.

"Many studies have shown this association," Furman said. "We've found a possible reason for why this may be so."

The researchers used data gathered from a long-term program begun 10 years ago by Mark Davis, a professor of microbiology and immunology and the director of the Stanford Institute for Immunity, Transplantation and Infection, and study co-author Cornelia Dekker, professor of pediatric infectious diseases, to study the immunology of aging. In that program, healthy participants ages 20-30 and another group older than 60 were monitored annually via surveys, blood draws and reviews of their medical histories.

For the new study, by zeroing in on two clusters of genes whose activity was associated with the production of a potent circulating inflammatory protein called IL-1-beta, the researchers compared blood drawn from older versus younger study participants to see which genes tended to be more highly activated in older people. The genes within each cluster appeared to work in coordination with one another.

The researchers found that incubating a type of immune cell with two of those nucleic-acid metabolites boosted activity in one of the gene clusters, resulting in increased IL-1-beta production. When injected into mice, the substances triggered massive systemic inflammation, along with high blood pressure. In addition, immune cells infiltrated and clogged the animals' kidneys, increasing renal pressure substantially.

"Our findings show that an underlying inflammatory process, which is associated with aging, is not only driving cardiovascular disease but is, in turn, driven by molecular events that we may be able to target and combat," Davis was quoted as saying in a news release from Stanford, which is located in Northern California on the U.S. west coast.

This inflammatory mechanism was found to be activated only in some, but not all, of the older study participants. Those in whom it was relatively quiescent tended to drink more caffeinated beverages. Laboratory experiments revealed that the mechanism was directly countered by caffeine and associated compounds.

Intrigued by the correlation between older participants' health, gene-cluster activation and self-reported rates of caffeine consumption, the researchers followed up and verified that blood from the group with low cluster activity was enriched for caffeine and a number of its metabolites, compared with blood from the group with high cluster activity.

Examples of these metabolites are theophylline, also found in tea, and theobromine, which abounds in chocolate.

Incubating immune cells with caffeine and its breakdown products along with the inflammation-triggering nucleic acid metabolites substantially prevented the latter from exerting their powerful inflammatory effect on the cells.

"That something many people drink - and actually like to drink - might have a direct benefit came as a surprise to us," said Davis, who noted that the study did not prove a causal link. "And we've shown more rigorously, in laboratory tests, a very plausible mechanism for why this might be so."