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: 5.48). 06/2013; 27(9):3879. DOI: 10.1096/fj.13-232066
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    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; DOI:10.1016/j.arr.2013.12.006 · 7.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Many of the aging-related morbidities, including cancer, cardiovascular disease, neurodegenerative disease, and infectious susceptibility, are linked to a decline in immune competence with a concomitant rise in proinflammatory immunity, placing the process of immune aging at the center of aging biology. Immune aging affects individuals older than 50 years and is accelerated in patients with the autoimmune disease rheumatoid arthritis. Immune aging results in a marked decline in protective immune responses and a parallel increase in tissue inflammatory responses. By studying immune cells in patients with rheumatoid arthritis, several of the molecular underpinnings of the immune aging process have been delineated, such as the loss of telomeres and inefficiencies in the repair of damaged DNA. Aging T cells display a series of abnormalities, including the unopposed up-regulation of cytoplasmic phosphatases and the loss of glycolytic competence, that alter their response to stimulating signals and undermine their longevity. Understanding the connection between accelerated immune aging and autoimmunity remains an area of active research. With increasing knowledge of the molecular pathways that cause immunosenescence, therapeutic interventions can be designed to slow or halt the seemingly inevitable deterioration of protective immunity with aging.
    Mayo Clinic Proceedings 04/2014; 89(4):563–575. DOI:10.1016/j.mayocp.2014.01.020 · 5.81 Impact Factor