Atorvastatin Therapy Modulates Telomerase Activity in Patients Free of Atherosclerotic Cardiovascular Diseases

Abstract

Background: Telomerase activity (TA) is considered as the biomarker for cardiovascular aging and cardiovascular diseases (CVDs). Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA. Until now, this effect has not been investigated in prospective randomized studies. We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells.Methods: In a randomized, placebo-controlled study 100 hypercholesterolemic patients, aged 35–75 years, free of known CVDs and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months. TA was measured by quantitative polymerase chain reaction.Results: At study end, 82 patients had sufficient peripheral blood mononuclear cells needed for longitudinal analysis. TA expressed as natural logarithms changed from 0.46 ± 0.05 to 0.68 ± 0.06 (p = 0.004) in the atorvastatin group and from 0.67 ± 0.06 to 0.60 ± 0.07 (p = 0.477) in the control group. In multiple regression analysis, atorvastatin therapy was the only independent predictor (p = 0.05) of the changes in TA independently of markers of chronic inflammation and oxidative stress. Atorvastatin therapy was associated with increases in interleukin-6 within the normal range and a tendency toward reduction in blood urea.Conclusion: These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector.Trial registration: The trial was registered in ISRCTN registry ISRCTN55050065.

Telomerase as a Therapeutic Target in Cardiovascular Disease

“…Telomerase activity was significantly increased in isolated PBMCs in the atorvastatin group, but did not change in the placebo arm. 111 In line with these results, we have shown that pharmacologically relevant concentrations of atorvastatin increased telomerase activity by 6 fold in human and mouse PBMCs and CD4 T-lymphocytes, translating into a moderate increase in proliferation of T lymphocytes. 103 The proliferative effect of atorvastatin was ablated in the absence of the catalytic subunit TERT.…”

Avaliação da Senescência de Células Sanguíneas Mononucleares Periféricas e na Disfunção Endotelial entre Adultos com Alto Risco Cardiovascular

“…Atualmente, estão sendo realizadas investigações para medir se estatinas podem ser utilizadas como possíveis agentes terapêuticos para a ativação da telomerase e como geroprotetores eficientes. 22 Recentemente, as células senescentes despertaram a atenção por seu potencial como alvo terapêutico para doenças relacionadas à idade, como as DCV. Estudos demonstraram que a senescência celular é equivalente à senescência epitelial, e, portanto, à senescência vascular.…”

The failure of “engineered rejuvenation”: laboratory genomics do not translate into precision anti-aging therapies

“…Examples include not only rejuvenation biotechnologies in general, but also anti-senescence drugs (senolytics) [27,28] such as quercetin, dasatinib, navitoclax [29] , drugs or compounds such as sirtuin modulators [30] , rapamycin [31] , lifespan-extending herbs [32] , metformin [33] , telomere and telomerase modulators [34] . A common characteristic of these is that there is a clear separation between an outside agent (a physician, surgeon, healer, nutritionist) and the patient (healthy or unhealthy young or older people).…”