Telomere biology in healthy aging and disease

Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen, The Netherlands.
Pflügers Archiv - European Journal of Physiology (Impact Factor: 4.1). 09/2009; 459(2):259-68. DOI: 10.1007/s00424-009-0728-1
Source: PubMed


Aging is a biological process that affects most cells, organisms and species. Telomeres have been postulated as a universal biological clock that shortens in parallel with aging in cells. Telomeres are located at the end of the chromosomes and consist of an evolutionary conserved repetitive nucleotide sequence ranging in length from a few hundred base pairs in yeast till several kilo base pairs in vertebrates. Telomeres associate with shelterin proteins and form a complex protecting the chromosomal deoxyribonucleic acid (DNA) from recognition by the DNA damage-repair system. Due to the "end-replication problem" telomeres shorten with each mitotic cycle resulting in cumulative telomere attrition during aging. When telomeres reach a critical length the cell will not further undergo cell divisions and become senescent or otherwise dysfunctional. Telomere shortening has not only been linked to aging but also to several age associated diseases, including tumorigenesis, coronary artery disease, and heart failure. In the current review, we will discuss the role of telomere biology in relation to aging and aging associated diseases.

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Available from: Wiek H van Gilst
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    • "Telomeres associate with shelterin proteins and form a complex protecting the chromosomes from erosion and end-to-end fusion [22]. Elucidating the relationship between shelterin proteins and telomere maintenance has been the goal of various investigations. "
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    ABSTRACT: Coccidiosis is considered to be a major problem for the poultry industry, and coccidiosis control is yet urgent. Due to the roles in telomere length regulation and end protection, telomere-binding proteins have been considered as a good target for drug design. In this work, a putative Gbp1p that is similar to telomeric DNA-binding protein Gbp (G-strand binding protein) of Cryptosporidium parvum, was searched in the database of Eimeria tenella. Sequence analysis indicated Eimeria tenella Gbp1p (EtGbp1p) has significant sequence similarity to other eukaryotic Gbps in their RNA recognition motif (RRM) domains. Electrophoretic mobility shift assays (EMSAs) demonstrated recombinant EtGbp1p bound G-rich telomeric DNA, but not C-rich or double-stranded telomeric DNA sequences. Competition and antibody supershift assays confirmed the interaction of DNA-protein complex. Chromatin immunoprecipitation assays confirmed that EtGbp1p interacted with telomeric DNA in vivo. Collectively, these evidences suggest that EtGbp1p represents a G-rich single-stranded telomeric DNA-binding protein in Eimeria tenella.
    Preview · Article · Sep 2014 · Biochemical and Biophysical Research Communications
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    • "Telomere length, or more precisely, the rate of telomere shortening, is a biomarker of biological aging [1] and eating nutrient-rich foods might delay aging process and reduces risk of many chronic diseases [2]. The role of telomere length in cellular senescence and development of chronic disease associated with physiological aging has been addressed in several studies [3], [4]. Although telomere length may predict clinical outcomes and mortality among humans, cells with shortened telomeres remain genetically stable if the telomere maintenance system, which includes mainly telomerase, is fully functioning [5]. "
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    ABSTRACT: Leukocyte telomere length (LTL) and rate of telomere shortening are known biomarkers of aging while, numerous studies showed that Mediterranean diet (MD) may boost longevity. We studied association between telomere length, telomerase activity and different adherence to MD and its effects on healthy status. The study was conducted in 217 elderly subjects stratified according Mediterranean diet score (MDS) in low adherence (MDS≤3), medium adherence (MDS 4-5) and high adherence (MDS≥6) groups. LTL was measured by quantitative polymerase chain reaction and telomerase activity by a PCR-ELISA protocol. High adherence group showed longer LTL (p = 0.003) and higher telomerase activity (p = 0.013) compared to others. Linear regression analysis including age, gender, smoking habit and MDS showed that MDS was independently associated with LTL (p = 0.024) and telomerase activity levels (p = 0.006). Telomerase activity was independently associated with LTL (p = 0.007) and negatively modulated by inflammation and oxidative stress. Indeed, telomerase levels were associated with healthy status independently of multiple covariates (p = 0.048). These results support a novel role of MD in promoting health-span suggesting that telomere maintenance, rather than LTL variability is the major determinant of healthy status among elderly.
    Full-text · Article · Apr 2013 · PLoS ONE
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    • "Telomeres are a nucleoprotein complex at the ends of linear chromosomes consisting of several kilobases of 5′-TTAGGG-3′ DNA repeats and telomere associated proteins collectively known as the shelterin complex [6, 7]. Shelterin assembles tightly on the telomere to prevent chromosomal instability and inhibit DNA damage machinery [8, 9]. Repeated rounds of mitosis or endogenous oxidative stress successively diminishes telomeric repeats resulting in critically short telomeres [10]. "
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    ABSTRACT: Cardiac regeneration following myocardial infarction rests with the potential of c-kit+ cardiac progenitor cells (CPCs) to repopulate damaged myocardium. The ability of CPCs to reconstitute the heart is restricted by patient age and disease progression. Increasing CPC proliferation, telomere length, and survival will improve the ability of autologous CPCs to be successful in myocardial regeneration. Prior studies have demonstrated enhancement of myocardial regeneration by engineering CPCs to express Pim-1 kinase, but cellular and molecular mechanisms for Pim-1-mediated effects on CPCs remain obscure. We find CPCs rapidly expand following overexpression of cardioprotective kinase Pim-1 (CPCeP), however, increases in mitotic rate are short-lived as late passage CPCePs proliferate similar to control CPCs. Telomere elongation consistent with a young phenotype is observed following Pim-1 modification of CPCeP; in addition, telomere elongation coincides with increased telomerase expression and activity. Interestingly, telomere length and telomerase activity normalize after several rounds of passaging, consistent with the ability of Pim-1 to transiently increase mitosis without resultant oncogenic transformation. Accelerating mitosis in CPCeP without immortalization represents a novel strategy to expand the CPC population in order to improve their therapeutic efficacy. STEM CELLS2012;30:2512-2522.
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