The Madrid Institute of Advanced Food Studies (IMDEA Alimentación), in Madrid, carried out a study that shows that harmol —a compound in the beta-carboline family— improves the function of the skeletal muscle and parameters metabolic associated with quality of life during aging.
According to research with the participation of the Health Research Institute (INCLIVA), treatment with harmol significantly increased life expectancy by two invertebrate models. In addition, it improved glucose tolerance, insulin sensitivity and hepatic lipid accumulation in a model of prediabetes. Between level changes neuromuscularIt was also possible to observe a very significant reduction in the frailty in elderly animals treated with harmol.
Harmol, like other beta-carbolines – known for their neurological effects – is present in many foodsincluding grains coffee, meat, fish or cerealsas well as in tobacco leaves. At the doses used in the study, harmol showed no toxicity and had few effects on the central nervous system, which is consistent with its poor ability to cross the blood-brain barrier and thus reach the brain.
Mitochondrial dysfunction causes the onset and progression of functional impairment associated with sarcopenia (loss of muscle mass and strength that occurs during aging) and geriatric frailty syndrome
At work, recently published in the journal Nature Communications, José Viña and María del Carmen Gómez Cabrera participated, among other researchers from different international scientific groups.
energetic collapse
Muscular aging is associated with an energy collapse that is explained by a change in mitochondriaone of the most relevant cellular components, as it is primarily responsible for cellular energy production. Mitochondrial dysfunction causes the onset and progression of functional impairment associated with sarcopenia (loss of muscle mass and strength that occurs with aging) and the geriatric frailty syndrome, which affects more than 33% of the population over 80 years of age.
Frailty affects activities of daily living and reduces the autonomy of those who suffer from it, which translates into a greater risk of disability, hospitalization and death. A frail elderly person compared to a robust one is more likely to become dependent and fatigue more easily than a young person, among other things, because their mitochondria stop working (they lose their ability to produce energy).
It’s a mechanism very similar to that activated by caloric restriction or exercise: they make the mitochondria work in a controlled way, and this makes them stronger.
O mitochondrial dysfunction associated with age can be modulated through different interventions aimed at keeping the mitochondria in good condition. These strategies are based on the induction of a mild mitochondrial stress that triggers a coordinated compensatory response between the nucleus and the mitochondria, resulting in an improvement in that function.
Harmol activates signaling pathways in cells that are ultimately able to improve mitochondria and metabolic parameters associated with quality in this phase of life.
IMDEA Food Research Group. /IMDEA
It is “a mechanism very similar to that activated by caloric restriction or exercise: they make the mitochondria work in a controlled manner, and this makes them stronger”, says Luís Filipe Costa-Machado, first author of the article.
For his part, Pablo J. Fernández-Marcos, the main person in charge of the project, highlights another interesting aspect of the discoveries: “with harmol we discovered that this effect of mitochondrial improvement is carried out by the cells through similar mechanisms to those who they make us feel happierbecause they share the same target proteins”. In his opinion, this opens up a very interesting field of research on the association between psychological status and aging.
Extend life in good health
“The aging of the population is, without a doubt, a great success”, says Gómez Cabrera. He adds: “We have managed to increase life expectancy in the last hundred years more than in the previous 2,000 years, especially in our country, which ranks alongside Japan and Switzerland as the third country with the highest life expectancy. However, the aging of the population is also a major challenge because we cannot extend life expectancy in good health”. The INCLIVA researcher maintains that “it is estimated that we are currently spending a 20% of our sick life” and that, in fact, “the main risk factor for almost all chronic diseases is aging”.
Research on aging “has advanced a lot in the last 30 years, after an eminently descriptive phase in which what happens when we get old was studied, it evolved into a mechanistic what are they studying molecular mechanisms by which we age”, explains the specialist. “Currently, we are in an intervention phase in which we do not intend to cure aging (we must keep in mind that we are talking about a physiological process, not a pathological one), but modulating it”.
Reference:
Costa-Machado, LF and others “Peripheral modulation of MAO-B and GABAAR antidepressant targets by harmol induces mitohormesis and delays aging in preclinical models”. Nature Communications (2023)