Dyskeratosis congenita (DKC) is a rare inherited disease of impaired telomere maintenance that progressively leads to multi-organ failure, including the bone marrow. By enhancing telomerase activity, androgen derivatives (ADs) are a potential therapeutic option able to re-elongate previously shortened telomeres. Danazol, oxymetholone, and nandrolone are ADs most frequently used to treat DKC. However, no direct in vitro analyses comparing the efficacy of these ADs have been conducted so far. We therefore treated mononuclear cells derived from peripheral blood and bone marrow of four patients with mutations in telomerase reverse transcriptase (TERT, n = 1),in the telomerase RNA component (TERC, n = 2) and in dyskerin pseudouridine synthase 1 (DKC1, n = 1) and found no substantial differences in the activity of these three agents in patients with TERC/TERT mutations. All AD studied produced comparable improvements of proliferation rates as well as degrees of telomere elongation. Increased TERT expression levels were shown with danazol and oxymetholone. The beneficial effects of all ADs on proliferation of bone marrow progenitors could be reversed by tamoxifen, an estrogen antagonist abolishing estrogen receptor-mediated TERT expression, thereby underscoring the involvement of TERT in AD mechanism of action. In conclusion, no significant differences in the ability to functionally enhance telomerase activity could be observed for the three AD studied in vitro. Physicians therefore might choose treatment based on patients’ individual co-morbidities, e.g., pre-existing liver disease and expected side-effects.

Obesity has negative effects on comorbidities, health-related quality of life and survival. Telomere length (TL) changes after bariatric surgery have been reported, but the studies are contradictory, and analyses using state-of-the art techniques for TL measurement, such as flow-FISH, are sparse. We measured TL dynamics via flow-FISH in patients undergoing bariatric surgery and compared their TL with 105 healthy individuals. Patients with obesity who underwent bariatric surgery were included. Lymphocyte and granulocyte absolute and age-adjusted (aa) TL were analyzed by flow-FISH before (preoperative cohort, n = 45) and after surgery (follow-up cohort, n = 35) at month 5.5 ± 3.9 (mean ± standard deviation [SD]). The initial lymphocyte aaTL was significantly shorter (-0.37 kb ± 0.18 kb, P = 0.045) in patients with obesity, while the granulocyte aaTL was not different from that in the healthy comparison population (0.28 kb ± 0.17 kb, P = 0.11). The telomere dynamics after surgery showed an increase in mean TL in both lymphocytes and granulocytes of patients with a pronounced BMI loss of ≥ 10 kg/m². We did not find any association between TL increase after surgery and age, sex or the type of procedure selected for bariatric surgery. We confirmed that patients suffering from obesity have significantly shorter lymphocyte TL using flow-FISH. Along with and dependent on the degree of weight reduction after bariatric surgery, TL significantly increased in both lymphocytes and granulocytes after a mean of 5.5 months. Our results show that bariatric surgery affects not only body weight but also biomarkers of aging, such as TL.