One of the processes associated with aging is progressive shortening of telomeres, DNA-protecting structures at the ends of chromosomes, like the plastic tips on shoelaces. Each time a cell divides, its telomeres get shorter. Eventually, the cell can’t replicate anymore and dies or becomes senescent. However, telomerase can keep the length of telomeres intact, even after cell division. Now, a study from researchers at University of São Paulo and the National Institutes of Health shows that sex hormones can stimulate production of this enzyme, telomerase. The team state that their findings suggest that the approach can combat the damage caused to the organism by telomerase deficiency. The opensource study is published in the New England Journal of Medicine.
Previous studies show that in an embryo, where tissue is still in the formative stage, telomerase is expressed by practically every cell. After this period, only cells that are constantly dividing, such as blood-forming stem cells, which can differentiate into a variety of specialized cells, continue to produce telomerase. Earlier studies from the lab showed that androgens, which are converted into estrogens in humans, bind to female hormone receptors in the telomerase gene promoter region and thereby stimulate expression of the enzyme in cells. The current study investigates whether this effect, observed in the lab, also occurs in humans.
The current study treated the patients with androgen instead of estrogen, as it has long been used as a drug in cases of congenital anemia and offers the advantage of stimulating an increase in red blood cells, which estrogen cannot do. Treatment with the steroid danazol, a synthetic male hormone, was tested for two years in 27 patients with aplastic anemia owing to telomerase gene mutations.
The group explain that in a healthy adult, telomere length varies from 7,000 to 9,000 base pairs on average. They go on to add that a normal person’s telomeres lose 50 to 60 base pairs per year, and a patient with telomerase deficiency can lose between 100 and 300 base pairs per year. Results show that in the patients who received danazol, telomere length increased by 386 base pairs on average over two years with a rise in hemoglobin mass. Data findings show that the improvement observed in these subjects was sufficient to rid them of transfusion dependency.
The team state that on completion of the protocol, the medication was interrupted, a fall in all counts was observed. Several patients resumed the medication with smaller doses, individually adjusted to minimize side-effects. They go on to add that in a new protocol currently in progress at the University of São Paulo, the same kind of approach is being tested with nandrolone, an injectable male hormone.
The team surmise that although the results of the study suggest that drugs can be used to reverse one of the biological drivers of aging, it is not yet clear whether the benefits of treatment would surpass the risks in healthy people, especially if the treatment involved the use of sex hormones. For the future, the researchers state that some groups, such as patients undergoing chemotherapy or radiotherapy, may benefit from drugs that stimulate telomerase in the future.
Source: University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP)
