Rejuvenation Recipe: More Notch and Less TGF-beta
Scientists at the University of California, working under the guidance of Dr. Irina Conboy, claim that manipulations of stem cells can restore youth to aging muscles. By changing one of the molecular mechanisms, they managed to make the stem cells of the muscle tissue of old mice produce new muscle fibers as well as it happens in a young body.
Any physical overstrain leads to damage to muscle cells, which are eventually replaced by new ones that appear as a result of stem cell division. However, in an aging organism, cells die faster than new ones appear.
Muscle tissue atrophy develops during aging, as well as in various diseases such as cancer and muscular dystrophy. Loss of muscle tissue often worsens overall health, so pharmaceutical companies are actively working on the creation of new drugs that stimulate the growth of muscle mass without the negative side effects characteristic of anabolic steroids.
In an earlier work, the authors demonstrated that placing aging stem cells in a culture containing vascular and muscle tissues of a young organism stimulates their ability to form new cells. Conversely, it turned out that aging tissue leads to premature aging of young stem cells and a significant slowdown in their division. The researchers suggested that the stem cells included in the young and old tissue receive different chemical signals, manipulations over which will allow the aging tissue to regain its youth.
In experiments on mice, researchers found that aging muscle tissue synthesizes an increased amount of transforming growth factor beta (TGF-beta), whose ability to suppress muscle growth has been known for a long time. Using the method of RNA interference, they blocked genes encoding molecules involved in the TGF-beta-mediated signaling mechanism inhibiting cell division in mice of the experimental group. After that, young and old animals were injected with small doses of snake venom, which instantly kills muscle cells.
The evaluation carried out five days later showed that the young animals were actively replacing damaged muscle cells with new ones.
A similar level of regeneration was observed in the old animals of the experimental group, while in the old animals of the control group, fibroblast proliferation and scar tissue formation occurred at the site of damage.
The upper figure shows the muscle tissue of an aging mouse processed using the RNA interference method, which obviously demonstrates more active growth compared to the tissue of the control animal depicted in the lower figure (muscle stem cells are shown in red, muscle fibers in green).
The authors believe that the control of the TGF-beta-mediated signaling mechanism can be used to treat age-related muscle atrophy.
However, they emphasize that complete blocking of this mechanism is fraught with serious side effects, including the development of tumors, so it is extremely important to find an acceptable balance between the activity of TGF-beta and Notch protein, known for its ability to rejuvenate aging tissues.
Both proteins bind to the same receptor on the surface of stem cells and are natural competitors.
A physiologically young organism is characterized by a high level of Notch and a low level of TGF–beta, and in old age this ratio changes to the opposite. Changes in the levels of these proteins are clearly associated with the aging process, but the causes and mechanisms of this are still unclear.
Notch and TGF-beta regulate the activity of stem cells and other organs, including the brain, so the proposed approach can theoretically be used, if not to rejuvenate the entire body, then at least to repair physical damage to soft tissues and eliminate the consequences of a stroke.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of UC Berkeley
18.06.2008