Cell Aging Reversed with Male Hormone in Clinical Trial

A new study conducted by scientists from Brazil and the United States suggests male hormone can boost availability of the enzyme telomerase, thus helping to reverse or slow down the aging process.

The study, whose findings were published in the famous New England Journal of Medicine, was aimed at ascertaining how male hormone can be useful to patients with diseases resulting from gene mutations, including pulmonary fibrosis and aplastic anemia. These sorts of mutations are those associated to telomerase deficiency.

The study authors observed that the strategy employed may be helpful for dealing with diseases associated to mutated genes arising from low levels of telomerase in the body.

Brazilian researchers headed by Rodrigo Calado worked in collaboration with US researchers at the National Institutes of Health (NIH) to carry out the study.

Telomerase and aging

Scientists have long associated aging to the progressive shortening of telomeres in the body. Telomeres are structures found at the ends of your chromosomes. They serve to protect the ends and your DNA from deterioration or fusion with nearby chromosomes. But as we get older, telomeres become shorter each time the cells they are associated to undergoes division. This continues until they get too short to replicate, thus losing their function or dying off. The result of this is aging. The length of a telomere is usually considered a measure of the age of a cell in laboratory settings. A healthy adult has an average telomere length in the range 7000-9000 base pairs. Under normal circumstances, around 55 base pairs are lost every year. But this can rise up to 300 base pairs per year in the presence of telomerase deficiency.

Telomerase is believed to help prevent reduction in telomere length, even after cell divisions take place. This means you may slow down your aging clock by maintaining sufficient amount of the reverse transcriptase enzyme, which some consider a "cellular elixir of youth." It has been observed that certain cells are able to guard against aging through the help of telomerase by adding DNA sequences to lengthen their telomeres.

Telomerase is more freely expressed by stem cells in an embryo, with tissue still in the process of formation. This enables the cells to divide repeatedly to enable the individual to form. But the enzyme is significantly expressed only in cells highly dependent on constant division, including sperm cells and blood-forming stem cells. A cell becomes senescent after reaching the Hayflick limit, which is put at between 50 and 70 divisions. Telomerase prevents your cells from reaching this limit.

Different types of gene mutations capable of speeding up the aging clock can result from insufficient telomerase.

"Aplastic anemia is one of the diseases that can be caused by telomerase deficiency," said Calado, a professor at the Ribeirao Preto Medical School of the University of Sao Paolo. "Bone marrow stem cells age prematurely and fail to produce enough red blood cells, white blood cells and platelets, making the patient dependent on blood transfusions and more susceptible to infections."

Reversing aging with male hormone

Along with his colleagues, Calado had in a 2009 article published in the journal Blood shown that androgens stimulate cell expression of telomerase, thereby helping to deal with aging. They noted that androgen, which converts to estrogen in humans, does this by binding to female hormone receptors found in the telomerase gene promoter region.

The present study was aimed at finding out if similar effect observed in the laboratory can also be achieved in humans. However, the researchers opted for androgen over estrogen in this clinical trial due to its popularity as a drug for congenital anemia. Also, unlike estrogen, androgen stimulates improvement in hemoglobin (red blood cells) mass.

The researchers treated 27 patients suffering from aplastic anemia linked to mutated genes resulting from telomerase insufficiency. These were administered a synthetic male hormone danazol. It was observed that those treated recorded an average increment of 386 base pairs over the two-year period of the study. You may say they rolled back 1-2 years of aging!

An improvement in the mass of hemoglobin was also noticed in the aplastic anemic patients. This rose from 9 g/dL to 11 g/dL on average. The enhanced level is slightly lower than the 12 g/dL minimum for a non-anemic person, but it was enough to remove needs for transfusions for survival.

Calado noted that a drop was noticed in all counts after the drug administration was halted. A number of the patients had to resume the medication at smaller doses adjusted to suit each individual with minimal side effects.

It is not entirely clear at this time whether the benefits of this strategy would outweigh associated risks in healthy individuals. But it is expected that certain groups of patients, including those receiving radiotherapy or chemotherapy, may find telomerase-stimulating drugs beneficial at a later date.

A somewhat similar strategy involving the use of an injectable male hormone, nandrolone, is also being investigated at the USP's Ribeirao Preto Blood Center.