2023 Author: Bryan Walter | [email protected]. Last modified: 2023-05-21 22:24
Effect of dimethoxychalcone (bottom panel) on yeast cell survival. Dead cells glow pink.
Austrian researchers found that the substance 4, 4-dimethoxychalcone from the flavonoid class slows down the aging of yeast cells, prolongs the life of invertebrates, and in mice reduces the zone of damage to the heart after ischemia. In nature, this substance is found in the leaves of the Angelica keiskei koidzumi plant, which is popular in folk medicine under the name ashitaba. Like many other gerontoprotectors, this substance works by activating autophagy in cells, the process of "self-eating" of intracellular structures, according to an article published in Nature Communications.
Among the components of plants, scientists have already discovered many substances that have a gerontoprotective effect on animal cells. Polyphenols such as resveratrol have been shown to reduce oxidative stress on cells, exert anti-inflammatory effects, and prolong the life of model invertebrates such as the nematodes Caenorhabditis elegans and the fruit flies Drosophila melanogaster, and even fish. In mammals, however, the beneficial properties of polyphenols in general, and of the largest class (flavonoids) in particular, have proven to be rather difficult to detect. Presumably, polyphenols can have anti-inflammatory and antitumor effects in mice, but they do not significantly affect life expectancy. As shown by meta-studies, intake of the same resveratrol in humans, on average, does not have a significant effect on health.
In search of flavonoid components that can slow down cellular aging, scientists from the University of Graz (Austria) analyzed another library of 180 substances. The researchers tested in yeast cells whether treatment with one component or another helps maintain membrane integrity, inhibit the production of reactive oxygen species, and maintain the ability to divide over time. In all parameters, the best results were shown by the substance 4, 4-dimethoxychalcone (DMC), which was not previously considered as a gerontoprotector.
In experiments on model invertebrates, the addition of DMC to food extended the life of nematodes and fruit flies by about 20 percent. In an experiment on mice, the scientists found that DMC partially protects the heart muscle - the area of ventricular damage after model ischemia in mice that were given the substance was smaller than in controls. At the same time, scientists did not record any changes in behavior and serious side effects when taking even high doses of DMC.
In their search for the mechanism of action of dimethoxychalcone, researchers found that, like many other gerontoprotectors, DMC works by activating autophagy in cells, the process of recycling waste cellular structures within autophagosomes. For the discovery and detailed description of this mechanism in 2016, the Japanese scientist Yoshinori Osumi was awarded the Nobel Prize.
The authors of the work did not reach experiments on humans, however, they found that in nature, DMC is found mainly in the leaves of the Japanese plant Angelica keiskei koidzumi, which, under the name ashitaba, is popular in Asian folk medicine as a general tonic.
Despite the wide range of substances and techniques that have been shown to slow aging in models, only chronic caloric restriction seems to have shown some positive effect on primates. Long-term experiments in rhesus monkeys have shown that this approach reduces the incidence of age-related diseases, and the US National Institute of Aging conducted a small two-year study in humans, during which moderate beneficial effects were found.