Telomeres Research Papers - Academia.edu (original) (raw)

Humans are keenly aware of their mortality. Given a limited time what we do with our life is a reflection of knowledge of our mortality. In 2009 the Nobel prize in medicine to Jack W Szostak, Elizabeth Blackburn, Carol W Greider for their... more

Humans are keenly aware of their mortality. Given a limited time what we do with our life is a reflection of knowledge of our mortality. In 2009 the Nobel prize in medicine to Jack W Szostak, Elizabeth Blackburn, Carol W Greider for their work on Telomerase and scientific research exploded in this area. Telomere protect chromosome ends the Telomerase enzyme maintains Teleomere length. This activity of Telomerase is essential in aging and stem cells and achieving longer life spans. Telomerase is expressed in 85% of human cancer cell lines, but its enzymatic activity is not detectable in most human somatic cells which constitute the vast majority of the cells in the human body. There is a need for increased telomerase activity in stem cells for use in the treatment of therapies where there is an active role for telomerase. Umbilical Cord Blood (UCB) provides an attractive source of stem cells for research and therapeutic uses. Work shown here characterizes the gene expression changes from Umbilical cord cells differentiate toward telomerase on treatment with Metadichol ®. Metadichol ® is a nanoemulsion of long-chain alcohols that is nontoxic. It is a mixture of long-chain alcohols derived from food. The work presented here is about the effect of Metadichol ® on Telomerase expression profile in Umbilical cord cells. Our results using q-RT-PCR show increases of mRNA telomerase expression by Sixteen-fold at one picogram but down-regulates expression at higher concentrations of 100 pg, 1 ng, 100 ng and one microgram per ml concentration. Western blot studies showed expression of Telomerase protein which is slightly higher than control at one picogram, i.e., Telomerase protein expression continues at replacement level. Since it is devoid of toxic effects, it can be directly tested on humans and is in use today as an immune boosting supplement. Metadichol ® increases expression of Klotho an anti-aging gene expression in cancer cell lines by Four to Tenfold , and Klotho gene has been documented to inhibits the growth of cancer cells. Metadichol ® also inhibits TNF, ICAM1, CCL2, and BCAT1 which that is associated with proliferation in yeast and increased metastatic potential in human cancers. It paves the way for safe clinical testing and research and study of Telomerase biology and its use in humans.

The telomere length can either be shortened or elongated by an enzyme called telomerase after each cell division. Interestingly, the shortest telomere is involved in controlling the ability of a cell to divide. Yet, its dynamics remains... more

The telomere length can either be shortened or elongated by an enzyme called telomerase after each cell
division. Interestingly, the shortest telomere is involved in controlling the ability of a cell to divide. Yet, its
dynamics remains elusive. We present here a stochastic approach where we model this dynamics using a
Markov jump process.We solve the forward Fokker-Planck equation to obtain the steady state distribution
and the statistical moments of telomere lengths. We focus specifically on the shortest one and we estimate
its length difference with the second shortest telomere. After extracting key parameters such as elongation
and shortening dynamics from experimental data, we compute the length of telomeres in yeast and obtain
as a possible prediction the minimum concentration of telomerase required to ensure a proper cell
division.

Lucrare interdisciplinară cu conţinut ştiinţific pe probleme de biologie, sănătate, dietă şi psihologie, redactată sub formă de naraţiune cu nuanţe umoristice, în anumite capitole, care dezvăluie evoluţia personalităţii autorului, de la... more

Lucrare interdisciplinară cu conţinut ştiinţific pe probleme de biologie, sănătate, dietă şi psihologie, redactată sub formă de naraţiune cu nuanţe umoristice, în anumite capitole, care dezvăluie evoluţia personalităţii autorului, de la primii ani ai vi---eţii, până în prezent, confruntarea cu boala şi suferinţele, urmată de prezentarea, cu detalii vii, a teoriei biotransformărilor, etapele de vindecare şi exemple concrete culese de la alte persoane care au reuşit să dobândească aceleaşi aptitudini, prin simpla lectură a publicaţiilor anterioare ale autorului. Aceasta este o ediţie aniversară a celor 10 ani de biotransformări în care autorul reactualizează şi reuneşte într-un singur volum, toate lucrările anterioare, renunţând la anumite capitole, mai puţin conectate experienţei sale directe, dar adăugând cel puţin 100 de pagini noi, cu informaţii recente, redactate pe baza noilor experimente din ultimii ani. Nu în ultimul rând, autorul îşi dezvăluie preocupările tehnice şi artistice care au contribuit la biotransformarea sa. Sunt incluse şi CV-ul autorului, precum şi câteva citate şi motto-uri din literatura ce a stat la baza căutărilor sale. Autorul doreşte să reformuleze şi să îmbunătăţească toate teoriile ştiinţifice conectate direct sau indirect cu experienţa sa de biotransformare, prezentând într-o altă interpretare şi/sau adăugire, o parte din conţinutul publicaţiei sale anterioare „Biotransformări sub influenţa psihicului”. La toate acestea, autorul a completat doar cu strictul necesar, anumite extrase din cartea anterioară, îmbunătăţite, adăugite şi reverificate.

Eukaryotic genomes are distributed on linear chromosomes that are grouped together in the nucleus, an organelle separated from the cytoplasm by a characteristic double membrane studded with large proteinaceous pores. The chromatin within... more

Eukaryotic genomes are distributed on linear chromosomes that are grouped together in the nucleus, an organelle separated from the cytoplasm by a characteristic double membrane studded with large proteinaceous pores. The chromatin within chromosomes has an as yet poorly characterized higher-order structure, but in addition to this, chromosomes and specific subchromosomal domains are nonrandomly positioned in nuclei. This review examines functional implications of the long-range organization of the genome in interphase nuclei. A rigorous test of the physiological importance of nuclear architecture is achieved by introducing mutations that compromise both structure and function. Focussing on such genetic approaches, we address general concepts of interphase nuclear order, the role of the nuclear envelope (NE) and lamins, and finally the importance of spatial organization for DNA replication and heritable gene expression.

The conversion of circular genomes to linear chromosomes during molecular evolution required the invention of telomeres. This entailed the acquisition of factors necessary to fulfill two new requirements: the need to fully replicate... more

The conversion of circular genomes to linear chromosomes during molecular evolution required the invention of telomeres. This entailed the acquisition of factors necessary to fulfill two new requirements: the need to fully replicate terminal DNA sequences and the ability to distinguish chromosome ends from damaged DNA. Here we consider the multifaceted functions of factors recruited to perpetuate and stabilize telomeres. We discuss recent theories for how telomere factors evolved from existing cellular machineries and examine their engagement in non-telomeric functions such as DNA repair, replication, and transcriptional regulation. We highlight the remarkable versatility of protection of telomeres 1 (POT1) proteins that was fueled by gene duplication and divergence events that occurred independently across several eukaryotic lineages. Finally, we consider the relationship between oxidative stress and telom-eres and the enigmatic role of telomere-associated proteins in mitochondria. These findings point to an evolving and intimate connection between telomeres and cellular physiology and the strong drive to maintain chromosome integrity.

Telomere is a DNA sequence at the end of linear chromosomes that provides stability and protects chromosomal ends during DNA replication. Telomeres shorten during DNA replication with each cell division. Once telomeres become critically... more

Telomere is a DNA sequence at the end of linear chromosomes that provides stability and protects chromosomal ends during DNA replication. Telomeres shorten during DNA replication with each cell division. Once telomeres become critically short, after about 50 to 75 cell divisions, a cell can no longer divide; that state is known as cellular senescence, and it is further followed by cellular apoptosis; that eventually leads to the aging of organs and tissues.
Two telomere maintenance mechanisms, telomerase and Alternative lengthening of telomeres (ALT), can rebuild telomeres, thus delaying the cellular senescence and counteracting the molecular clock of aging set by the telomere shortening. Both mechanisms were first discovered in cancerous cells. However, recent findings suggest that telomere maintenance and elongation may be activated in normal, non-cancerous, cells.
Search for therapies that could counteract the telomere shortening has uncovered that a number of well-known nutrients positively impact telomere length. One of those nutrients is polyunsaturated marine Omega-3 fatty acids, an essential nutrient that has to be obtained either from food or supplements. Omega-3s are an important structural component of all cell membranes. In addition to their structural role in the cell membrane, Omega-3s also participate in gene expression, neurogenesis, multiple signaling pathways, immune function, anti-inflammation, and cellular growth. Numerous studies have been conducted of the health benefits of the Omega-3 fatty acids, and the research provides evidence that these fatty acids may help fight inflammation, help lower the risk of, prevent and treat cardiovascular disease, rheumatoid arthritis, triglycerides and blood pressure, and help prevent dementia, Alzheimer's disease, and diabetes. Recent studies also suggest that consuming Omega-3s positively correlates with the telomere length.
This review attempts to briefly cover currently known information, including latest findings, on 1) telomeres, telomerase, alternative telomere lengthening, 2) polyunsaturated marine Omega-3 fatty acids, their functional roles in human bodies and known health benefits, 3) describe studies that demonstrated promising action of Omega-3s in fighting cellular senescence at the telomeric DNA level, and 4) suggest potential mechanisms behind this action of Omega-3.

Telomeres are tandem repeat DNA sequences located at distal ends of chromosomes that protect against genomic DNA degradation and chromosomal instability. Excessive telomere shortening leads to cellular senescence and for this reason... more

Telomeres are tandem repeat DNA sequences located at distal ends of chromosomes that protect against genomic DNA degradation and chromosomal instability. Excessive telomere shortening leads to cellular senescence and for this reason telomere length is a marker of biological age. Abnormally short telomeres may culminate in the manifestation of a number of cardio-metabolic diseases. Age-related cardio-metabolic diseases attributable to an inactive lifestyle, such as obesity, type 2 diabetes mellitus and cardiovascular disease, are associated with short leukocyte telomeres.
Exercise training prevents and manages the symptoms of many cardio-metabolic diseases whilst concurrently maintaining telomere length. The positive relationship between exercise training, physical fitness and telomere length raises the possibility of a mediating role of telomeres in chronic disease prevention via exercise. Further elucidation of the underpinning molecular mechanisms of how exercise maintains telomere length should provide crucial information on how physical activity can be best structured to combat the chronic disease epidemic and improve the human health span. Here, we synthesise and discuss the current evidence on the impact of physical activity and cardiorespiratory fitness on telomere dynamics. We provide the molecular mechanisms with a known role in exercise-induced telomere length maintenance and highlight unexplored, alternative pathways ripe for future investigations.

The causal role of aneuploidy in cancer initiation remains under debate since mutations of euploidy-controlling genes reduce cell fitness but aneuploidy strongly associates with human cancers. Telomerase activation allows immortal growth... more

The causal role of aneuploidy in cancer initiation remains under debate since mutations of euploidy-controlling genes reduce cell fitness but aneuploidy strongly associates with human cancers. Telomerase activation allows immortal growth by stabilizing telomere length, but its role in aneuploidy survival has not been characterized. Here, we analyze the response of primary human cells and murine hematopoietic stem cells (HSCs) to aneuploidy induction and the role of telomeres and the telomerase in this process. The study shows that aneuploidy induces replication stress at telomeres leading to telomeric DNA damage and p53 activation. This results in p53/Rb-dependent, premature senescence of human fibroblast, and in the depletion of hematopoietic cells in telomerase-deficient mice. Endogenous telomerase expression in HSCs and enforced expression of telomerase in human fibroblasts are sufficient to abrogate aneuploidy-induced replication stress at telomeres and the consequent induction of premature senescence and hematopoietic cell depletion. Together, these results identify telomerase as an aneuploidy survival factor in mammalian cells based on its capacity to alleviate telomere replication stress in response to aneuploidy induction.

shorter. Telomere length is mainly maintained by telomerase. This enzyme is present in high concentrations in the embryonic stem cells and in fast growing embryonic cells, and declines with age. It is still unclear to what extent there is... more

shorter. Telomere length is mainly maintained by telomerase. This enzyme is present in high concentrations in the embryonic stem cells and
in fast growing embryonic cells, and declines with age. It is still unclear to what extent there is telomerase in adult stem cells, but since these
are the founder cells of cells of all the tissues in the body, understanding the telomere dynamics and expression of telomerase in adult stem cells
is very important.
In the present communication we focus on telomere expression and telomere length in stem cells, with a special focus on mesenchymal stem
cells. We consider different mechanisms by which stem cells can maintain telomeres and also focus on the dynamics of telomere length in
mesenchymal stem cells, both the overall telomere length and the telomere length of individual chromosomes.


The chromosome replication process causes the ends of chromosomes to slowly degrade without the remediative action of the enzyme telomerase. Telomeres are repetitive sequences at the ends of chromosomes that protect them from... more

The chromosome replication process causes the ends of chromosomes to slowly degrade without the remediative action of the enzyme telomerase. Telomeres are repetitive sequences at the ends of chromosomes that protect them from inappropriate DNA repair and cellular responses to DNA damage. Telomerase and other telomere-associated proteins are essential for end protection, chromosome maintenance and telomere regeneration. Two telomere protection complex proteins, TRF1 and PinX1, have been found to interact and to negatively regulate telomere length in humans. Human PinX1 is a direct inhibitor of telomerase enzymatic activity, while TRF1 indirectly regulates telomerase by preventing access to the telomeric overhang. Xenopus laevis has previously been shown to have constitutive telomerase activity in somatic cells, making it an excellent model organism for research on telomerase and telomere length regulation. This study sought to investigate the interaction of the telomeric proteins TRF1 and PinX1 in Xenopus laevis. An in vitro expression construct for a Myc-epitope tagged TRF1 dimerization domain was created to aid in the study of this interaction. This construct can be used in future studies for more specific identification of interacting domains, should PinX1 and full-length TRF1 be found to interact in X. laevis. The interaction of X. laevis PinX1 and full-length TRF1 was investigated using previously cloned constructs. Immunoprecipitation and coimmunoprecipitation studies were performed to investigate in vitro interaction. While no conclusive evidence was found either for or against interaction, progress was made towards a rigorous experimental design to test this interaction.

The programmed aging paradigm interprets aging as a function favored by natural selection at a supraindividual level. This function is implemented, according to the telomere theory, through mechanisms that operate through the sub... more

The programmed aging paradigm interprets aging as a function favored by natural selection at a supraindividual
level. This function is implemented, according to the telomere theory, through mechanisms that operate through the sub
telomere–telomere–telomerase system. After reviewing some necessary technical and ethical reservations and providing a
concise description of aging mechanisms, this work considers interventions that could lead to the control of some highly dis
abling characteristics of aging, such as Alzheimer’s and Parkinson’s syndromes and agerelated macular degeneration, and
afterwards to a full control of aging up to a condition equivalent to that of the species defined as “with negligible senes
cence”. The various steps needed for the development of such interventions are described along general lines.

Variations in telomeres, and especially their shortening, is a well-known process that marks the rhythm of life in all living things, but the reason behind telomere lengthening in some cases is not so well understood. We only know that it... more

Variations in telomeres, and especially their shortening, is a well-known process that marks the rhythm of life in all living things, but the reason behind telomere lengthening in some cases is not so well understood. We only know that it is directly related to the activation of an enzyme called telomerase. Variations in microgravity could partially explain this phenomenon, and be part of the cause of its activation.

Epidemiological studies have demonstrated age differences among human adults in susceptibility to radiation, with cancer cases attributable to radiation being more frequent for older individuals at time of exposure. In addition to the... more

Epidemiological studies have demonstrated age differences among human adults in susceptibility to radiation, with cancer cases attributable to radiation being more frequent for older individuals at time of exposure. In addition to the notion that susceptibility increases because of progressive decline in DNA monitoring and immunosurveillance, telomere function is now emerging as a new and important factor in modulating cellular and organism sensitivity to ionizing radiation. The link between telomeres and radiosensitivity is well-documented in humans, but the causal events remain elusive. In this paper, it is shown that irradiated human epithelial cells with short dysfunctional telomeres derived from normal mammary gland display elevated DNA damage. An approach identifying the specific chromosomes with critically shortened telomeres in each donor has allowed us to conclude that short dysfunctional telomeres in human epithelial cells join radiation-induced DNA broken ends, thus interfering with their efficient repair. These findings argue against telomeres participating as sensors or transducers of DNA damage, as previously suggested. Rather, our current findings give support to the idea that dysfunctional telomeres, by acting as an additional joining option, reduce the repair fidelity of DNA broken-ends induced by radiation throughout the genome. In the mammary gland, age-dependent telomere attrition due to epithelial turnover, together with the accretion of checkpoint deficiencies, might render the accumulation of short dysfunctional telomeres. This implies that the risks associated with mammography screening could be higher than previously assumed. Our results have the possibility of imprinting a temporal dimension onto radiation sensitivity, namely, that shortened telomeres in aged cells may more easily compromise normal tissue function in the elderly.

Nóbelsverðlaunin í lífeðlis- og læknisfræði 2009 skiptust jafnt á milli þriggja Bandaríkjamanna, þeirra Elizabeth H. Blackburn (University of California, San Francisco), Carol W. Greider (John Hopkins University School of Medicine,... more

Nóbelsverðlaunin í lífeðlis- og læknisfræði 2009 skiptust jafnt á milli þriggja Bandaríkjamanna, þeirra Elizabeth H. Blackburn (University of California, San Francisco), Carol W. Greider (John Hopkins University School of Medicine, Baltimore) og Jack W. Szostak (Harvard Medical School Boston; Howard Hughes Medical Institute). Verðlaunin voru veitt fyrir uppgötvun á byggingu og starfsemi litningaenda og ensímsins telómerasa. Fyrstu rannsóknir byggðu á notkun einfrumunga. Niðurstöður verðlaunahafanna leystu m.a. tvö vandamál lífefnafræðinnar sem tengjast því að litningar eru línulegar sameindir, þ.e. hvernig litningar eru varðir fyrir niðurbroti og hvernig eftirmyndun á litningaendum á sér stað.

Colorectal cancer (CRC) is a very frequently diagnosed pathological entity, registering an elevated incidence rate each year. CRC stems from both a genetic and an environmental background, exhibiting divergent molecular and biological... more

Colorectal cancer (CRC) is a very frequently diagnosed pathological entity, registering an elevated incidence rate each year. CRC stems from both a genetic and an environmental background, exhibiting divergent molecular and biological phenotypes, and rendering its therapy, follow-up and prognosis a demanding task. Telomerase, a complex consisting of the catalytic protein human telomerase reverse transcriptase (hTERT) and the mRNA template hTERC, is related to the preservation of telomere length (TL). A wide range of studies suggest that hTERT also partakes in signalling pathways relevant to proliferation and apoptosis. Thus, the potent role of telomerase as a biomarker for CRC behaviour emerges as a reasonable inquiry.

Biochemistry of the Spirit giving Life. // Биохимия Духа, дарящего Жизнь.

Los telómeros son estructuras cromatínicas especializadas ubicadas en los extremos de los cromosomas eucariontes. El DNA como las proteínas que lo constituyen, presentan las características que los diferencian de otros cromosomas. Estos... more

Los telómeros son estructuras cromatínicas especializadas ubicadas en los extremos de los cromosomas eucariontes. El DNA como las proteínas que lo constituyen, presentan las características que los diferencian de otros cromosomas. Estos parecen estar implicados en diversas funciones celulares, relacionadas con el control de la vida de diferentes estirpes celulares. Estas estructuras se replican de tal manera que, durante el ciclo celular, gracias a la acción de enzimas denominadas telomerasas, que están formadas por proteínas y RNA. En estudios recientes, se ha estudiado el comportamiento de estos telómeros y las telomerasas en el cáncer y en el envejecimiento. En este trabajo, se presentará un resumen de varios artículos, donde se expondrán los principales hallazgos sobre la estructura de los telómeros, sus funciones y la acción de las telomerasas.

Although numerous studies suggest that religious involvement is associated with a wide range of favorable health outcomes, it is unclear whether this general pattern extends to cellular aging. In this paper, we tested whether leukocyte... more

Although numerous studies suggest that religious involvement is associated with a wide range of favorable health outcomes, it is unclear whether this general pattern extends to cellular aging. In this paper, we tested whether leukocyte telomere length varies according to several dimensions of religious involvement. We used cross-sectional data from the Nashville Stress and Health Study (2011-2014), a large probability sample of 1,252 black and white adults aged 22 to 69 living in Davidson County, TN, USA. Leukocyte telomere length was measured using the monochrome multiplex quantitative polymerase chain reaction method with albumin as the single-copy reference sequence. Dimensions of religious involvement included religiosity, religious support, and religious coping. Our multivariate analyses showed that religiosity (an index of religious attendance, prayer frequency, and religious identity) was positively associated with leukocyte telomere length, even with adjustments for religious support, religious coping, age, gender, race, education, employment status, income, financial strain, stressful life events, marital status, family support, friend support, depressive symptoms, smoking, heavy drinking, and allostatic load. Unlike religiosity, religious support and religious coping were unrelated to leukocyte telomere length across models. Depressive symptoms, smoking, heavy drinking, and allostatic load failed to explain any of the association between religiosity and telomere length. To our knowledge, this is the first population-based study to link religious involvement and cellular aging. Although our data suggest that adults who frequently attend religious services, pray with regularity, and consider themselves to be religious tend to exhibit longer telomeres than those who attend and pray less frequently and do not consider themselves to be religious, additional research is needed to establish the mechanisms underlying this association.

DNA secondary structures containing regions of single-stranded DNA have now been identified in the genomic DNA of a number of prokaryotic and eukaryotic species, including humans. Many of these secondary structures are associated with... more

DNA secondary structures containing regions of single-stranded
DNA have now been identified in the genomic DNA of a number of prokaryotic and eukaryotic species, including humans. Many of these
secondary structures are associated with regions of DNA involved in regulation of transcription: promoters or upstream elements. The secondary structures involved appear likely to be hairpin or cruciform structures that may be recognition sites for binding of transcription factors. In the case of the coliphage N4 virion RNA polymerase, a defined hairpin in the polymerase promoter necessary for binding of the polymerase and regulation of transcription has been shown to be extruded
under physiological conditions in plasmid DNA. The presence of single-stranded DNA in the promoters of several species suggests that regulatory hairpins may be involved in transcription of a number of genes. In support of this, hairpin- or cruciform-binding proteins have been identified from several species. These results imply that secondary structures in regulatory regions may be targets for drugs that bind and either block or enhance binding of proteins involved in transcription. In this review, we discuss the evidence for DNA secondary structures, particularly hairpins and cruciforms, in genomic DNA and review the studies to date of development of small molecules that can selectively bind these structures.

The review considers the structure of telomeres, terminal regions of linear of linear chromosomal DNA. Features of nucleotide organization of telomeric DNA in different species are shown. Special attention is given to analysis of... more

The review considers the structure of telomeres, terminal regions of linear of linear chromosomal DNA. Features of nucleotide organization of telomeric DNA in different species are shown. Special attention is given to analysis of functions of separate mammal and Saccharomyces cerevisiae telomere proteins, and their role in telomere length regulation and protection against degradation.

Objective: Mounting evidence suggests that higher optimism is associated with reduced risk of age-related morbidities and premature mortality. However, possible biological mechanisms underlying these associations remain understudied. One... more

Objective: Mounting evidence suggests that higher optimism is associated with reduced risk of age-related morbidities and premature mortality. However, possible biological mechanisms underlying these associations remain understudied. One hypothesized mechanism is a slower rate of cellular aging, which in turn delays age-related declines in health. Methods: We used data from two large cohort studies to test the hypothesis that higher optimism is associated with longer leukocyte telomere length. With cross-sectional data from the Health and Retirement Study (HRS; n = 6417; mean age = 70 years) and the Women's Health Initiative (WHI; N = 3582; mean age = 63 years), we used linear regression models to examine the association of optimism with relative telomere length (assessed in leukocytes from saliva [HRS] or plasma [WHI]). Models adjusted for sociodemographics, depression, health status, and health behaviors. Results: Considering both optimism and telomere length as continuous variables, we found consistently null associations in both cohorts, regardless of which covariates were included in the models. In models adjusting for demographics, depression, comorbidities, and health behaviors, optimism was not associated with mean relative telomere length (HRS: β = −0.002, 95% confidence interval = −0.014 to 0.011; WHI: β = −0.004, 95% confidence interval = −0.017 to 0.009). Conclusions: Findings do not support mean telomere length as a mechanism that explains observed relations of optimism with reduced risk of chronic disease in older adults. Future research is needed to evaluate other potential biological markers and pathways.

diverse number of disorders are amenable to this approach, including haematopoietic, neurological and cardiovascular diseases, as well as bone defects and diabetes. Central to the success of cell therapy is the necessity to be able to... more

diverse number of disorders are amenable to this approach, including haematopoietic, neurological
and cardiovascular diseases, as well as bone defects and diabetes. Central to the
success of cell therapy is the necessity to be able to identify, select, expand and manipulate
cells outside the body. Recent advances in adult stem cell technologies and basic biology
have accelerated therapeutic opportunities aimed at eventual clinical applications. Adult
stem cells with the ability to differentiate down multiple lineages are an attractive alternative
to human embryonic stem cells (hES) in regenerative medicine. In many countries,
present legislation surrounding hES cells makes their use problematic, and indeed the origin
of hES cells may represent a controversial issue for many communities. However, adult
stem cells are not subject to these issues. This review will therefore focus on adult stem
cells. Based on their extensive differentiation potential and, in some cases, the relative ease
of their isolation, adult stem cells are appropriate for clinical development. Recently, several
observations suggest that multipotential adult stem cells are capable of producing a
whole spectrum of cell types, regardless of whether or not these tissues are derived from
same germ layer; highlighting the opportunity to manipulate stem cells for therapeutic use.

Telomeric DNA progressively erodes with each round of cell division in cells that do not express telomerase, a specialized reverse transcriptase necessary to fully duplicate the chromosomal ends. Telomerase is expressed in tumor cells but... more

Telomeric DNA progressively erodes with each round of cell division in cells that do not express telomerase, a specialized reverse transcriptase necessary to fully duplicate the chromosomal ends. Telomerase is expressed in tumor cells but not in most somatic cells and thus telomeres and telomerase may be proposed as attractive targets for the discovery of new anticancer agents. In this paper we will present different strategies to inhibit telomerase activity via an interaction with a telomere / telomerase nucleic acid component, with a special emphasis on quadruplex ligands.