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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Available from: Virginia Boccardi, Nov 13, 2015
    • "This pattern of longer RTL was observed in almost each single subgroup of eGFR and UACR category with reasonable sample size (Table 2). Finally, we investigated whether the difference in RTL between the groups with the longest and the intermediate disease duration is influenced by the frequency of prescribed medications which are described to have either an effect on telomere length or telomerase activity (Boccardi et al., 2013; Olivieri et al., 2012; Moores et al., 2011; Pusceddu et al., 2015; Paul et al., 2015). There was no difference in the frequency of statins, vitamin D or analogs, folic acid, and vitamin B1, B6 or B12. "
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    ABSTRACT: Telomere length is considered as a biological marker for aging. It is expected that telomeres shorten with age and with conditions associated with oxidative stress and inflammation. Both are present in patients with chronic kidney disease (CKD) who have a very high cardiovascular risk. We investigated whether CKD duration is associated with relative telomere length (RTL) in 4802 patients from the German Chronic Kidney Disease (GCKD) study. We measured RTL in each sample in quadruplicates using a quantitative polymerase chain reaction (qPCR). We observed a U-shaped association of RTL with CKD duration: the longest RTL was found in those 339 patients who reported the shortest disease duration (<6months) and shorter RTL in 2108 patients with duration between 6months and less than 5years. Most importantly, those 2331 patients who reported a CKD duration of 5years and more had significantly longer RTL compared to those with intermediate CKD duration (6months to less than 5years): mean 0.954, 95%CI 0.946-0.961 versus 0.937, 95%CI 0.929-0.944, p=0.002). Due to the cross-sectional nature of the study these surprising results have to be considered with caution and as hypothesis-generating. Whether the longer RTL in patients with long-lasting disease is caused by an activation of telomerase to counteract the shortening of RTL due to oxidative stress and inflammation or whether they are caused by a survival bias needs to be investigated in longitudinal studies. Our data are in support of a higher plasticity of shortening and elongations of RTL as until recently anticipated.
    Experimental gerontology 10/2015; 72. DOI:10.1016/j.exger.2015.09.019 · 3.49 Impact Factor
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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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