A new pleiotropic effect of statins in elderly: Modulation of telomerase activity

Department of Internal Medicine, Surgical, Neurological, Metabolic Disease and Geriatric Medicine, Second University of Naples, Naples, Italy.
The FASEB Journal (Impact Factor: 5.04). 06/2013; 27(9):3879. DOI: 10.1096/fj.13-232066
Source: PubMed


Recent evidence suggests a link between statins and telomere biology. Whether statin treatment may modulate telomerase activity and affect telomere erosion rate is unknown. We aimed at investigating the potential impact of statin therapy on peripheral blood mononuclear cells telomerase activity, its implication on LTL variability, and its association with telomere shortening rates along with aging. The cross-sectional study was conducted in 230 subjects (age range: 30-86 y) stratified according to statins treatment. LTL was measured by quantitative polymerase chain reaction and telomerase activity by a PCR-ELISA protocol. Subjects on statin treatment showed higher telomerase activity (P<0.0001) and longer LTL (P=0.028) levels compared to the nonstatin group. Statin therapy was associated with higher telomerase activity independently of multiple covariates, including age, gender, smoking habits, lipid, systemic inflammation, glucose, and blood pressure levels (P=0.019). Indeed, subjects on statin treatment showed significant lower telomere erosion along with aging. Every 1 y increment in age, LTL decreases by 0.058 Kb in no statin and 0.033 Kb in statin groups, respectively, as well as the major difference in telomere attrition between groups was found after the age of 65 yr (P<0.0001). In summary, statins, modulating telomerase activity, affect telomere erosion along with aging.-Boccardi, V., Barbieri, M., Rizzo, M.R., Marfella, R., Esposito, A., Marano, L., Paolisso, G. A new pleiotropic effect of statins in elderly: modulation of telomerase activity.

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    • "Telomere length was found to be longer in patients under statin therapy compared to those without [29]. A recent study of 230 subjects showed that statin therapy was associated with higher telomerase activity independently of multiple covariates, including age, gender, cardiovascular risk factors and systemic inflammation [30]. In the same study, subjects on statin treatment also showed significant lower telomere erosion along with ageing. "
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    ABSTRACT: Statins are one of the most potent drugs in delaying age-related inflammatory changes in the arterial vessel wall, slowing down the progression of atherosclerosis. Statins have also been shown to abrogate telomere-attributed cardiovascular risk. The goal of our study was to explore a potential effect of atorvastatin on telomerase activity in peripheral blood mononuclear cells (PBMCs) and T-lymphocytes (T cells). Methods and Results Treatment with pharmacologically relevant concentrations (0.1-0.3 μM) of atorvastatin resulted in a 6-fold increase of telomerase activity (TA) (p<0.0001) in human and mouse PBMCs and CD4 T cells, translating into moderate proliferation of T lymphocytes. In contrast, high doses of atorvastatin (2 - 5 μM) or the addition of LDL cholesterol completely inhibited proliferation, thereby abrogating telomerase activity. The proliferative effect of atorvastatin was ablated by the absense of the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT). Using transgenic GFP-mTert reporter mice, we observed a decrease in telomerase-positive lymphocytes from 30% to 15% during the first 5 months of age (p<0.01). This suggests that the decrease in immune cell turnover during normal development and maturation is mirrored by a reduction in telomerase activity in lymphocytes in-vivo. Conclusion Atorvastatin and cholesterol have opposing effects on telomerase in mononuclear cells and T-lymphocytes. Our study suggests a link between cholesterol metabolism and telomere-related cardiovascular risk.
    Atherosclerosis 10/2014; 236(2). DOI:10.1016/j.atherosclerosis.2014.07.020 · 3.99 Impact Factor
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    • "This is the first study revealing a direct correlation between telomere length and telomerase activity and identifying in this latter, rather than telomere length, the major determinant of a healthy status. The second study conducted in a population cohort with an average age of 64 years demonstrated that subjects under statin therapy had higher levels of telomerase activity, longer telomeres and slower telomere shortening rate compared with control group not taking this drug (Boccardi et al., 2013b). "
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    ABSTRACT: The elderly population is increasing progressively. Along with this increase the number of age related diseases, such as cardiovascular, neurodegenerative diseases, metabolic impairment and cancer, is also on the rise thereby negatively impacting the burden on health care systems. Telomere shortening and dysfunction results in cellular senescence, an irreversible proliferative arrest that has been suggested to promote organismal aging and disabling age-related diseases. Given that telomerase, the enzyme responsible for maintaining telomere lengths, is not expressed at levels sufficient to prevent telomere shortening in most of our cells, telomeres progressively erode with advancing age. Telomerase activation, therefore, might serve as a viable therapeutic strategy to delay the onset of cellular senescence, tissue dysfunction and organismal decline. Here we analyze the more recent findings in telomerase activation as a potential key modulator for human healthspan and longevity.
    Ageing research reviews 05/2014; 15(1). DOI:10.1016/j.arr.2013.12.006 · 4.94 Impact Factor
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    ABSTRACT: Aberrations in telomere length and telomere maintenance contribute to cancer development. In this article, we review the basic principles of telomere length in normal and tumor tissue and the presence of the two main telomere maintenance pathways as they pertain to gastrointestinal tract cancer. Peripheral blood telomeres are shorter in patients with many types of gastrointestinal tract cancers. Telomere length in tumor DNA also appears to shorten early in cancer development. Tumor telomere shortening is often accompanied by telomerase activation to protect genetically damaged DNA from normal cell senescence or apoptosis, allowing immortalized but damaged DNA to persist. Alternative lengthening of telomeres is another mechanism used by cancer to maintain telomere length in cancer cells. Telomerase and alternative lengthening of telomeres activators and inhibitors may become important chemopreventive or chemotherapeutic agents as our understanding of telomere biology, specific telomere-related phenotypes and its relationship to carcinogenesis increases.
    Expert review of gastroenterology & hepatology 11/2013; 7(8):733-48. DOI:10.1586/17474124.2013.848790 · 2.42 Impact Factor
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