Senolytics for diabetics

The number of old cells in the adipose tissue of diabetics was reduced in two weeks

Polina Loseva, N+1

Biologists from the Mayo Clinic have published the results of the third clinical trial of senolytics – drugs that should selectively destroy old cells in tissues. Nine patients with diabetes and kidney failure took senolytics for three days, and after 11 days, the researchers found that there were fewer old cells in their adipose tissue. This is the first experimental confirmation that senolytics perform their direct function in humans, scientists write in the journal EBioMedicine.

Old (or senescent) cells are considered to be one of the causes of age-related pathologies in the human body. This is a group of cells that do not multiply, do not die, do not perform their assigned functions in the tissue, but cause inflammation. You can fight them with the help of senolytic drugs: they block the mechanisms by which senescent cells resist death.

Senolytics have already proved themselves well in experiments on mice: with their help, it was possible to destroy old cells in various tissues, including fatty and nervous, as well as prolong the life of animals by 36 percent. 

Only two clinical trials have been conducted on humans so far. In January 2019, scientists from the Mayo Clinic reported on the successful use of senolytics in patients with pulmonary fibrosis: the physical condition of the subjects improved, although lung function did not recover. In June 2019, Unity Biotechnology told about the testing of senolytics in patients with osteoarthritis: subjective pain sensations have become weaker, although physiological indicators – for example, the concentration of pro–inflammatory substances in the blood - have changed insignificantly.

Now a group of researchers from the Mayo Clinic, led by James Kirkland, has summed up the interim results of the third clinical trial. Its participants are nine patients with chronic renal failure, which is caused by diabetes. According to the authors of the experiment, two senolytics – dasatinib and quercetin – were supposed to improve kidney function in the long term.

After the first course of drugs (taking for three days), the scientists decided to check whether there were changes in the tissues of patients. Previous clinical trials evaluated only subjective sensations and the quality of the organs, but did not check the main thing – whether senolytics destroy their immediate target. This time, the researchers took not only blood plasma from the patients for analysis, but also a biopsy of the skin and adipose tissue, where especially many senescent cells are formed in obesity and diabetes.

The researchers found that 11 days after taking senolytics, the number of old cells decreased. Their presence was determined in various ways (through the expression of characteristic genes or staining with specific markers) and, depending on the method of assessment, their number in adipose tissue decreased by 17-62 percent, and by 20-31 percent – in the skin.

Senescent cells are also known for their ability to cause inflammation and attract immune cells into the tissue. Therefore, scientists measured the number of macrophages in adipose tissue: in relation to the actual fat cells, they were 28 percent less than before taking senolytics. The amount of pro-inflammatory substances that old cells secrete into the blood has also decreased.

Nothing is yet known about the long-term effects of taking senolytics for diabetes. Nevertheless, already at the early stages it is clear that these drugs work at the cellular level: this suggests that the successes of previous clinical trials are also directly related to the destruction of old cells.

Senolytics are one of the so–called possible "medicines for old age": like all such remedies, they have to be tested on people with age-related diseases. If they prove to be effective against specific diseases – osteoarthritis, diabetes or others – then it will be possible to further study how they affect other aging processes in the body of the subjects. According to this principle, one recent study was conducted: patients were trying to restore the work of the thymus (an organ of the immune system) with a combination of drugs, and in the process it turned out that their epigenetic age was reduced by several years.

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