New anti-aging promise: study shows benefits of harmol, a compound in coffee

Harmon, a compound present in foods such as coffee, must be added to the list of promising molecules to achieve healthy aging..

A new study in cell lines and animal models suggests that the substance can extend life expectancy, reduce age-related frailty, and improve various metabolic parameters related to quality of life during aging.. Details of the research are published in the latest issue of the journal Nature Communications.

Led by researchers from the Madrid Institute for Advanced Food Studies, IMDEA Alimentación, with the participation of the INCLIVA Health Research Institute of Valencia, the study is the first to show these benefits.

“Until now these properties of the compound were not known. It is an example of all the compounds with interesting properties that remain to be discovered and developed,” confirms Pablo Fernández Marcos, head of the Biopromet Metabolic Syndrome Group at IMDEA Alimentacion, and principal investigator of this work.

The scientist indicates the steps that have been taken in this investigation. “We first tested harmol in cells in culture, to reduce the use of animals as much as possible, where we described its molecular properties and how it works inside the cell.. Subsequently, it was experimented on invertebrate models (flies and worms), with very short life times, around 1 month, in which we verified that it extended the life of these animals”.

Finally, in mouse models, they observed that harmol protected against diabetes caused by obesity (type 2), and that very old mice treated with harmol showed surprising protection from muscle fragility, a very serious problem in the elderly.” .

Harmol -a compound from the beta-carboline family known for its neurological effects- improves skeletal muscle function and metabolic parameters associated with quality of life during aging.

Treatment with this compound, in addition to extending life expectancy in the two invertebrate models, improved, as Fernández Marcos anticipated, glucose tolerance, insulin sensitivity, and hepatic lipid accumulation in a model of prediabetes. Among the changes at the neuromuscular level, a very significant reduction in frailty has been found in old treated animals.

On the potential beneficial implications of harmol for the general population and more especially for the elderly, the IMDEA Food researcher explains that the described product is “natural and present in coffee and other foods. We are not sure if the amounts present in food can activate these healthy processes or if, by contract, higher amounts are required. There is still a lot to study. On the other hand, this work is one more grain of sand to strengthen the concept that keeping mitochondria healthy throughout life is a good strategy against aging”.

The secret: keep mitochondria healthy

Harmol, like other beta-carbolines, is present in many foods including coffee beans, meat, fish or cereals, as well as tobacco leaves.. At the doses used in the study, harmol showed no toxicity and very little central nervous system effects, consistent with its poor ability to cross the blood-brain barrier and thus reach the brain.

The research indicates that muscular aging is associated with an energetic collapse that is explained by an alteration in the mitochondria, one of the most relevant cellular components, since it is the main responsible for the energy production of the cells.. Mitochondrial dysfunction causes the appearance and progression of functional deterioration associated with sarcopenia or loss of muscle mass and power that occurs during aging, and the geriatric frailty syndrome, which affects more than 33% of the population over 80 years of age. .

A frail elderly person, compared to a robust one, is more likely to end up being dependent and fatigues more easily than a young person, among other things, because their mitochondria stop being functional, they lose the ability to produce energy.

Age-associated mitochondrial dysfunction can be modulated through different interventions aimed at maintaining mitochondria in good condition.. These strategies are based on the induction of mild mitochondrial stress that triggers a coordinated compensatory response between the nucleus and mitochondria, resulting in improved mitochondrial function.

Fernández Marcos explains that in the work they describe harmol as a mitohormetic: a compound that causes moderate stress in the mitochondria, which initially damages it slightly. This moderate stress triggers responses from the entire cell that, in the medium term, makes the mitochondria more resistant and work better.. It is the mechanism that exercise or caloric restriction follow. When these stimuli are repeated over time, the body manages to have healthy mitochondria.”

Luis Filipe Costa-Machado, from IMDEA Alimentación, also comments on another interesting aspect of the study: it has been discovered that this mitochondrial improvement effect “is carried out by cells through mechanisms similar to those that make us feel happier, since they share the same target proteins. This opens up an interesting field of research on the association between psychological state and aging.”

Based on the findings on harmol, one of the unknowns is whether it is possible to obtain substances through food that allow healthy physiological aging.. For Fernández Marcos, in all known organisms, the most effective way to achieve healthy aging is caloric restriction. It is about following a varied diet with all the essential nutrients; but consume fewer calories than are considered 'normal'.

“This triggers a wide variety of healthy processes for aging: among other things, it prevents the accumulation of fat in the tissues, the mitochondria remain strong, or a cellular cleaning mechanism called autophagy is activated. That is to say: no eating too much helps us age better.