The fountain of youth? Researchers have discovered a new class of drugs that delay aging and extend active life in mice

The researchers, from the Scripps Institute and the Mayo Clinic, discovered that certain compounds succeed in killing aging cells, whose refusal to die causes the symptoms of aging. Further animal experiments are still needed before a clinical trial can be carried out

A team of researchers from the Scripps Medical Research Institute, Mayo Clinic and other institutes have identified a new class of drugs, which significantly slow down the aging process, soothe symptoms of weakness, improve heart function and extend the duration of a healthy and active life (healthspan).

The new study was published yesterday, March 9, on the website of the journal Aging Cell. The researchers coined the name senolytics for the new class of drugs. The prototype senolytic agents have demonstrated their ability to inhibit features associated with aging," says Prof. James Kirkland, who co-authored the study. "They may end up delaying, preventing, alleviating or even reversing many aging diseases at the same time and not just one at a time.

Senescent cells - cells that have stopped dividing (Senescent cells) accumulate with age and accelerate the aging process. Since the healthy period in mice was extended thanks to the elimination of these senescent cells, the scientists estimate that finding drugs that do the same action in humans may have great potential.

However, the scientists were faced with the issue of how to identify and damage the aging cells without harming other cells. The team suspected that the senescent cells' resistance to death as a result of obstruction or damage could serve as a clue. Indeed, through sequence analysis, they discovered that like cancer cells, aging cells overexpress "pro-survival networks" that help them resist programmed cell death (apoptosis). This finding provides an important criterion for the search for possible remedies.
After entering the criteria into the search considerations, the researchers came upon two possible compounds - the anti-cancer drug dasatinib (sold under the trade name Sprycel) and quercetin, a natural compound sold as a nutritional supplement that acts as an antihistamine and anti-inflammatory.

Further experiments in cell cultures showed that these compounds do promote the death of aging cells. The two compounds had different strengths. Dasatinib eliminated the senescent stem cells responsible for the formation of fat cells, while quercetin was more effective against senescent endothelial cells and against stem cells from the bone marrow of mice. A combination of the two has proven to be most effective.

In the next step, the researchers examined the effect of these substances on the health and aging process of mice. "In an animal model, the compounds improved cardiovascular function and endurance, reduced calcium leakage and weaknesses, and increased healthspan," says Prof. Laura Niedernhofer - one of the researchers who signed the article, "it can be noted that in several cases, the drugs achieved these improvements after one treatment.

In old mice, heart activity was improved within five days after a single dose of the drugs. One dose of the drug combination led to an improvement in physical activity in animals weakened after radiation such as that given to cancer patients. The effect lasted at least seven months after the drug treatment.

Administering the drugs regularly to the mice delayed age-related symptoms such as spinal erosion and calcium loss from the bones and increased the animals' healthy lifespans.

The researchers say that further animal experiments are required before clinical trials can be carried out. They also warn that both drugs studied have side effects, at least when given in long-term therapy.

However, despite these concerns, the researchers are satisfied with the results. "Cell aging is associated with a large number of diseases so there may be many options for treatments with these drugs and similar compounds" says Robbins. "Also, we expect that the treatment with senolytic drugs will be rare and thus it will be possible to reduce the risk of side effects."

"We see the research as a big step towards the development of treatments that can extend the duration of healthy life or treat age-related diseases and disorders." Says Prof. Paul Robbins from the Scripps Institute, who together with Prof. Laura Niedernhofer led the research at the Scripps Center in Florida. "When the senolytic agents, such as the combination we identified, are used clinically, the consequences can change the face of society." Niedernhofer added.

For information on the Scripps Institute website

More of the topic in Hayadan:

• stop aging - a series by Dr.Roey Tsezana
• Researchers at the Technion succeeded in stopping the aging of the immune system in mice
• Ray Kurzweil at the iNNOVEX 2015 conference: Life extension is expected to come in three stages: stopping aging diseases, DNA programming and nanotechnology inside the body