06 May 2014

Blood as a source of youth: new data

It is quite possible that the elixir of youth is one of the blood proteins. Numerous experiments on mice have shown that the introduction of the blood of young relatives to old animals can reverse or weaken some manifestations of aging (see, for example, the article "Young blood is really the source of youth").

An experimental technique known as parabiosis, which consists in combining the circulatory systems of two animals by a surgical method, was developed about 150 years ago. About 10 years ago, Amy Wagers, who was working at Stanford University at the time, and her colleagues gave parabiosis a second life, using it to study the aging processes of blood stem cells and muscle tissue. To their surprise, they found that combining the circulatory systems of a young and an old mouse rejuvenated the muscle stem cells of the latter. After that, the researchers published several papers describing the positive effect of young blood on the state of aging organs, including the liver, spinal cord and brain.

Subsequently, scientists at Harvard University, led by the same Amy Vagers, managed to identify the growth factor contained in the blood, which partly causes the rejuvenating effect of young blood on the heart muscles. In their latest work, the same research group demonstrated the ability of this factor to rejuvenate skeletal muscles and the brain of mice.

 


Reconstruction of the blood vessels of the brain of an old mouse (left) and an old mouse,
the bloodstream of which received the blood of a young animal (right)
(figure from the article by Lida Katsimpardi et al.).

A little later, the staff of the Vagers laboratory isolated a protein from the blood of mice, which, in their opinion, at least partially provides the rejuvenating effect of the blood of young animals. This protein, growth differentiation factor 11 (GDF11), is known for its involvement in the management of stem cell activity. It is found in large quantities in the blood of young animals, but its concentration decreases with age. Last year, the authors demonstrated that GDF11 injections reduce the severity of thickening of the heart wall, which is a characteristic manifestation of aging in mice. Now they have shown that this growth factor contributes to the restoration of muscle tissue damage in old mice, and also improves their results when passing running tests and grip strength tests. At the same time, the results obtained were comparable with the effects of parabiosis.

As part of a parallel series of experiments, the researchers demonstrated the ability of GDF11 to stimulate the growth of new blood vessels and olfactory neurons in the brains of mice. The result of this was an increase in the acuity of the animals' sense of smell. The authors claim that both in muscle tissue and in the brain, the positive effect of GDF11 is partly due to the restoration of stem cell functionality.

To date, convincing evidence of the ability to reverse aging-associated changes in various tissues has been obtained only for two approaches: taking rapamycin and a low-calorie diet. The authors believe that the use of GDF11 may be a safer alternative, since this compound is found in the blood. Harvard University has applied for patents on GDF11, and researchers are already negotiating the commercialization of GDF11 as a treatment for diseases such as Alzheimer's disease and heart disease. The production of such a drug will require the synthesis of a huge amount of therapeutic protein, therefore, the authors note that it is advisable to use its modified form or to influence the GDF11-mediated signaling mechanism using another molecule. They believe that this task is solvable, since the most difficult problem was the identification of the target signaling mechanism.

However, GDF11 already has a potential competitor. As part of an independent study, Stanford University scientists working under the guidance of Dr. Tony Wyss-Coray demonstrated the ability of parabiosis to rejuvenate the hippocampus, the region of the brain responsible for the formation and storage of memories. After the procedure of parabiosis with a young mouse, new interneuronal synapses were actively formed in the hippocampus of old animals. The authors have not yet been able to identify the anti-aging factor, but they have proposed a viable alternative. Experiments have shown that the administration of blood plasma from young animals to old mice has a similar effect on hippocampal neurons. This improves the results demonstrated by animals when passing learning and memorization tests.

According to Wiss-Corey, the introduction of blood plasma is a routine medical practice, so this approach, unlike the use of a new protein drug, does not require approval by the U.S. Food and Drug Administration. Researchers have already begun planning a small clinical trial in which patients with Alzheimer's disease will receive a series of injections of blood plasma from young donors. They also note that experiments on a mouse model of the disease have already demonstrated the positive effect of such therapy.

Article by Saul A Villeda et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice published in the journal Nature Medicine; articles by Lida Katsimpardi et al. Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors and Manisha Sinha et al. Restoring Systematic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle published in the journal Science.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Science NOW: Young Blood Renews Old Mice.

06.005.2014

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