Researchers propose new caffeine mode of action in protecting ageing heart

These conclusions were reached by a German team, whose research with mice identify caffeine as promoting protein movement into mitochondria, enhancing their function and protecting CV cells.

According to the researchers, as little as four cups of coffee may be enough to induce this physiologically relevant effect in humans.

"Our results indicate a new mode of action for caffeine,"​ said professor Judith Haendeler, group leader at the Leibniz Institute for Environmental Medical Research Düsseldorf, "one that promotes protection and repair of heart muscle through the action of mitochondrial p27. ​

“These results should lead to better strategies for protecting heart muscle from damage, including consideration of coffee consumption or caffeine as an additional dietary factor in the elderly population. ​

“Furthermore, enhancing mitochondrial p27 could serve as a potential therapeutic strategy not only in cardiovascular diseases but also in improving healthspan."​

Further work found caffeine to exhibit these protective qualities in pre-diabetic, obese mice, and in aged mice.

No direct human observations ​

Scrutinising the findings, Dr Ian Johnson, nutrition researcher and Emeritus fellow at Quadram Institute Bioscience, pointed out that the new work made no direct observations on humans, and did not confirm that consumption of coffee at any level had overall health benefits.

It was a view shared by Kevin McConway, Emeritus professor of applied statistics at The Open University.

“It’s really important not to read too much into these results.  They are certainly interesting, but on their own they can’t go far in establishing whether or how coffee drinking might reduce risks to human health.”​

“Several observational studies on people have found an association between drinking coffee and reduced risk of some diseases, including cardiovascular diseases such as heart attacks,”​ he added.

“The snag is that it’s impossible to be sure whether the reduced risk is caused by the coffee drinking, or instead by some other factor that just happens to be associated with drinking coffee.” ​

The identification of mitochondrial p27 is particularly noteworthy considering its presence in mitochondria found in the major cell types of the heart and its role as an inhibitor of the cell cycle.

In these cells, mitochondrial p27 appears to trigger the conversion of fibroblasts into cells containing contractile fibres—crucial for repair of heart muscle after a heart attack.

The research team found that caffeine induced the movement of p27 into mitochondria, setting off this chain of events, and did so at a concentration achievable for humans.

Caffeine’s role in health ​

The physiological role of caffeine has featured in a number of cohort studies​​ that have demonstrated its role in lowering risk​​ of developing type 2 diabetes.

Coffee consumption have also shown that consumption of caffeinated coffee is associated with lower risk​​ for coronary heart disease mortality, specifically in older​​ subjects.

The beneficial effect of caffeine appeared to be dose-dependent, as coffee consumption of 4 cups or more per day resulted in a further reduced risk for adverse events when compared to lower coffee consumption.

Mechanisms suggested in the past that explain the protective effects of caffeine have been attributed to its antagonist activity on adenosine receptors and the inhibition of phosphodiesterase enzymes.

“This new study discovers how a particular molecule in the body could affect processes inside cells, and showing how that is affected by caffeine (as found in coffee),”​ Professor McConway added.

“This does make it a bit more plausible that drinking coffee could cause improvements in human health – but the new study was carried out in mice, and in cells in the laboratory which were mostly derived from mice (though some cells originating from human sources were involved).”  ​

“Even if these processes work the same way in human bodies as in mouse bodies and cell cultures – and I think that might be a big if – it’s still not clear whether drinking coffee by aging humans will work in this way to protect our heart health.”​

Source: PLOS Biology

Published online ahead of print: doi.org/10.1371/journal.pbio.2004408​​

“CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system—New mode of action for caffeine.”​

Authors: Ale-Agha N, Goy C, Jakobs P, Spyridopoulos I, Gonnissen S, Dyballa-Rukes N, et al