Harmol is a compound from the beta-carboline family, known for its neurological effects, found in many foods, including coffee beans, meat, fish, or cereals, as well as tobacco leaves. New research by Spanish scientists has discovered that this substance improves skeletal muscle function and metabolic parameters associated with quality of life during aging.
The study has been led by the IMDEA Food Institute and has had the participation of the INCLIVA Health Research Institute of Valencia and CIBERFES (Centro de Investigación Biomédica en Red de Fragility y Envejecimiento Saludable), and has shown that treatment with harmol increased significantly increased life expectancy in two invertebrate models and that treatment with this substance also improved glucose tolerance, insulin sensitivity, and hepatic lipid accumulation in a prediabetes model.
In addition, among the changes at the neuromuscular level, a very significant reduction in frailty could be observed in old animals treated with harmol. 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 findings have been published in Nature Communications.
The challenge of extending life expectancy with good health
Muscular aging is associated with an energetic collapse related to an alteration in the mitochondria, one of the most important cellular components, since it is responsible for the production of energy in the cells. Mitochondrial dysfunction causes the appearance and progression of functional impairment associated with sarcopenia (loss of muscle mass and power that occurs during aging) and frailty syndrome, which affects more than 33% of those over 80 years of age.
Harmol activates signaling pathways in cells that are capable of improving mitochondria and metabolic parameters associated with quality of life during aging
Frailty is characterized by a reduced ability to respond to minor stress situations that affects activities of daily living and reduces the autonomy of those affected, which increases the risk of disability, hospitalization and death. A frail elderly person is more likely to become dependent and fatigue 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 by various 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. Harmol activates signaling pathways in cells that, ultimately, are capable of improving mitochondria and metabolic parameters associated with quality of life during aging.
According to IMDEA Alimentación researchers, “it is a mechanism very similar to that activated by caloric restriction or exercise: they make the mitochondria work in a controlled way, and that makes them stronger,” says researcher Luis Filipe Costa-Machado, first article author. Dr. Pablo J. Fernández-Marcos, the main person in charge of the project, also highlights another interesting aspect of the study: “With harmol we have 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 a very interesting field of research on the association between psychological state and aging”.
Dr. Gómez Cabrera, from INCLIVA, highlights the importance of this type of research aimed at contributing to healthy aging. “The aging of the population is, without a doubt, a great success. We have managed to increase life expectancy more in the last 100 years than in the previous 2,000 years, especially in our country, which ranks next to Japan and Switzerland as the third country with the longest lifespan. However, the aging of the population is also a great challenge because we have not been able to extend life expectancy in good health. It is estimated that we currently spend 20% of our lives sick. In fact, the main risk factor for almost all chronic diseases is aging ”, she highlights.
“Research on aging has come a long way in the last 30 years. After an eminently descriptive phase in which what happens when we age has been studied, it has evolved into a mechanistic phase in which the molecular mechanisms by which we age are being studied”, adds Gómez Cabrera, who concludes that “we are currently facing a intervention phase in which we intend not to cure aging, we must take into account that we are talking about a physiological process, not a pathological one, but modulating aging”.
Source: INCLIVA Health Research Institute, of Valencia and CIBERFES (Centre for Biomedical Research in Frailty and Healthy Aging Network)
