Telomere structure, function and maintenance
Telomeres are heterochromatic structures located at the ends of linear chromosomes formed by DNA tandem repeats bound by specialized protein complexes, which exert a protective function. A proper telomere structure prevents chromosome ends from being recognized as DNA strand breaks, thus preventing illegitimate homologous recombination between telomeres as well as chromosome end-to-end fusions1. In vertebrates, telomeric DNA is composed of up to thousands of TTAGGG hexanucleotide repeats that are bound by a six-protein complex known as shelterin, which encompasses TRF1, TRF2, POT1, TIN2, TPP1, and RAP12. TRF1 and TRF2 directly bind double-stranded telomeric repeats, whereas POT1 recognizes the single-stranded telomeric G-rich 3’ overhang. TIN2 binds to TRF1 and TRF2 through distinct domains and also recruits a TPP1-POT1 heterodimer, thus bridging different shelterins to organize the telomere cap2. Finally, RAP1 is recruited to telomeres by TRF2, but can also bind throughout chromosome arms to regulate transcription, playing an important role in protection from obesity and metabolic syndrome in mice3–5. Interestingly, all shelterins except RAP1 are essential for life6–8, owing to the fact that RAP1 is the only shelterin dispensable for telomere protection3,9,10.
Telomeres are proposed to be further stabilized by the formation of a protective T-loop lariat structure. The single-stranded 3’ overhang loops back and invades double-stranded telomeric DNA in a TRF2-dependent manner11,12. Thus, the T-loop sequesters the ends of chromosomes and provides a mechanism to prevent the full activation of a DNA damage response typically observed at most types of DNA ends13.
Importantly, owing in part to the so-called “end replication problem”, telomeres shorten during each cell duplication cycle due to the inability of replicative DNA polymerases to fully replicate the 3’ ends of linear chromosomes14,15. In particular, the removal of RNA primers, which provide the required 3’OH group for addition of dNTPs by DNA polymerases, renders the newly synthesized DNA strand shorter than the parental template. Thus, chromosomes progressively shorten from both ends upon repeated cell division, a process which in the context of the organism contributes to progressive telomere shortening with aging in all cell types where it has been studied16. When telomeres reach a critically short length they are detected by the DNA repair systems as DNA damage and elicit cell cycle arrest and cell death responses17. Thus, telomere shortening underlies the “molecular clock” proposed by Hayflick to explain the limited lifespan of cells in culture, or “Hayflick limit”17,18.
Telomerase is a DNA reverse transcriptase polymerase (telomerase reverse transcriptase [TERT]) which uses an RNA template (telomerase RNA component [TERC]) for de novo addition of telomeric DNA onto telomeres, thus compensating for the telomere erosion caused by cell divisions19. Indeed, overexpression of telomerase is sufficient to counteract telomere attrition and to indefinitely extend the replicative lifespan of primary cells in culture in the absence of genomic instability, transforming them into cancerous cells20–22. However, high telomerase expression is normally restricted to early stages of embryonic development (i.e. the blastocyst stage in mice and humans) and to pluripotent embryonic stem cells23,24. Thus, adult mammalian tissues including adult stem cell compartments do not express sufficient amounts of telomerase to maintain telomere length throughout organismal lifespan. Consequently, telomere shortening occurs along with physiological aging in humans and mice and this process is proposed to underlie aging and age-associated diseases as well as organismal longevity25,26.
In addition to the core components TERT and TERC, the telomerase holoenzyme further consists of the accessory dyskerin complex composed of the proteins DKC1, NOP10, NHP2, and GAR127,28, which also play essential roles in telomere biology. Holoenzyme assembly is thought to occur in the Cajal bodies29, and subsequently TCAB1 and TPP1 are required for proper trafficking of telomerase to telomeres. Moreover, the discovery of a long non-coding telomeric repeat-containing RNA, TERRA30,31, which has been proposed to regulate various aspects of telomere function, adds yet another level of complexity to telomere regulation32,33. Another crucial issue in telomere stability and maintenance is the replication of telomeric DNA, for which a myriad of proteins are required. Key factors in telomeric DNA replication are the CST complex (comprising the proteins CTC1, STN1, and TEN1)34,35, which facilitates telomere replication and simultaneously limits telomerase activity. WRN is a helicase with 3′ to 5′ exonuclease activity, which is also required for efficient telomere replication36 as well as processing of the 3’ telomeric overhang37,38. The helicase BLM contributes to telomere stability by resolving late replication structures39, whereas FEN1 and RTEL1 function in Okazaki fragment processing40 and T-loop disassembly during replication41, respectively. We recently published an in-depth review on the role of these proteins in telomere replication including the consequences for telomere maintenance if their function is impaired42.
In this review, we will discuss the role of telomeres in the origin of age-associated diseases and organismal longevity, as well as the potential use of telomerase as a therapeutic target to delay aging and to prevent and treat age-related diseases.
Telomeres as hallmarks of aging and longevity
Aging is a multifactorial process that results in a progressive functional decline at cellular, tissue, and organismal levels. During recent years, a number of molecular pathways have been identified as main molecular causes of aging, including telomere attrition, cellular senescence, genomic instability, stem cell exhaustion, mitochondrial dysfunction, and epigenetic alterations, among others26. Interestingly, telomere attrition is considered a primary cause of aging, as it can trigger all the above-mentioned hallmarks of aging, although the degree to which it is a principal cause of aging is under active investigation26. Critical telomere shortening elicits the induction of cellular senescence or the permanent inability of cells to further divide, which in turn has been proposed to be at the origin of different disease states17,43. In addition, telomere attrition in the stem cell compartments results in the exhaustion of their tissue- and self-renewal capacity, thus also leading to age-related pathologies44,45. Indeed, when this telomere exhaustion occurs prematurely owing to germline mutations in telomere maintenance genes (i.e. telomerase or shelterin genes), this triggers a premature loss of the renewal capacity of tissues leading to the so-called telomeropathies or telomere syndromes, including aplastic anemia and pulmonary fibrosis, among others46–49. Loss of DNA damage checkpoints can also allow the propagation of cells with short/damaged telomeres, thus leading to chromosome end-to-end fusions and genomic instability, as well as age-associated diseases like cancer50,51. A link between dysfunctional telomeres and mitochondrial compromise has been also proposed through transcriptional repression of the PGC-1α and PGC-1β genes by short telomeres, thus linking dysfunctional telomeres to mitochondrial aging52. Finally, short telomeres can trigger epigenetic changes at telomeric as well as subtelomeric chromatin53. In this regard, epigenetic regulation of telomeres has been described in processes that involve de-differentiation and loss of cellular identity such as during tumorigenesis54, as well as during the induction of pluripotency55. In particular, loss of heterochromatic marks at telomeres results in telomere elongation and increased telomere recombination53.
Of note, in addition to the persistent DNA damage response elicited by critically short telomeres, it recently became evident that a large proportion of DNA damage in stress-induced senescence resides in telomeres. Importantly, this DNA damage is independent of telomere length and accumulates with aging in primates and mice, suggesting that stress-induced and telomere length-independent senescence may contribute to the aging process too56,57.
In addition to being considered a primary molecular cause of aging, telomere shortening with time has been proposed to be a biomarker of biological aging, with a potential prognostic value for many different age-associated diseases, including cardiovascular failure58–64. Interestingly, telomere length has also been proposed as a marker of longevity. A study longitudinally following telomere length throughout the lifespan of individual zebra finches demonstrated that telomere length at day 25 after birth is a strong predictor of individual lifespan in this species65. In mice, a similar longitudinal follow up of telomere length throughout lifespan showed the rate of increase of short telomeres with time but not average telomere length or the rate of telomere shortening was predictive of individual lifespan66. This study also showed for the first time that laboratory wild-type mice shortened telomeres at a pace that was 100-fold faster than humans, thus providing a potential explanation for shorter lifespans in mice (2–3 years) compared to humans, in spite of their long telomere length at birth (~50–150 kb in mice versus ~15–20 kb in humans)67,68. A similar scenario was found in dogs, where telomere shortening has been described to be 10-fold faster than in humans69. These findings suggest that it is the ability of different species to maintain telomeres rather than average telomere length per se that may be determinant of species longevity. This idea is further supported by longitudinal studies in free-living birds. In particular, in Seychelles warblers, telomeres shorten throughout life and higher rates of telomere shortening predict mortality70. Similarly, survival in jackdaws can be predicted by nestling telomere shortening but not by absolute telomere length71.
Additional and independent evidence that the ability to maintain telomeres may determine mouse longevity came from the description of an age-specific metabolic signature predictive of chronological age in wild-type mice72. In particular, when this signature was used to predict the age of either telomerase-deficient or TERT-overexpressing mice, it predicted older or younger ages than their chronological age, respectively, in agreement with shorter telomeres and shorter lifespan in the telomerase-deficient mice, and longer telomeres and extended lifespan in the TERT-overexpressing mice72, thus suggesting that telomere length is a determinant of aging in wild-type mice.
In humans, a large number of cross sectional epidemiological studies confirmed telomere shortening with aging in humans16,73. Recently published data from the GERA cohort (Genetic Epidemiology Research on Adult Health and Aging), which comprises more than 100,000 individuals, further confirmed this correlation and also showed that telomere length correlates positively with survival in subjects older than 75, i.e. longer telomeres provide more years of life74. This is in agreement with a previous report showing that telomere length positively correlates with better median survival in individuals who are 60 years of age or older75. However, contradictory reports exist which do not support the correlation between average telomere length and the prediction of remaining years of life in the old and oldest76,77. In this regard, lessons from other species (mice, birds) show the importance of determining not only average telomere length but also longitudinal changes in telomere length as well as changes in the abundance of short telomeres. Thus, future epidemiological studies should take individual telomeres and their change over time into account (i.e. the rate of increase of the fraction of short telomeres). In this regard, methods that can quantify the presence of short telomeres, like the high-throughput quantitative telomere fluorescence in situ hybridization (FISH) technique58 or single telomere length analysis (STELA)78 will be important for establishing telomere shortening as a biomarker of human aging.
Intrinsic and environmental instigators of telomere length
As mentioned above, there are differences in the pace of telomere shortening across species, which indeed may contribute to explaining their different longevities, at least in part. The average telomere shortening in human blood cells occurs at a rate of 31–72 base pairs per year79,80 while mouse telomeres shorten around a hundred times faster than that66. This indicates that, in addition to the intrinsic end replication problem, there are other factors contributing to telomere attrition. In particular, oxidative damage may severely impact on telomere length. Cells exposed to oxidative stress conditions (e.g. H2O2, chronic hyperoxia) display accelerated telomere shortening and reduced replicative lifespans, whereas antioxidant treatment has the opposite effect81. In humans, the choice of lifestyle can influence telomere shortening. As an example, smoking, an unhealthy diet (e.g. high cholesterol, alcohol intake), or obesity might lead to telomere shortening by provoking tissue inflammation and oxidative stress82–87. Moreover, accelerated telomere shortening in leukocytes has been associated with psychological stress. In particular, patients with depression disorders have shorter telomeres compared to healthy individuals88, and this telomere erosion is found in all lymphocyte subpopulations of the adaptive immune system89. Stress provoked by physical abuse of children has been also associated with telomere shortening90. Furthermore, there is a wealth of studies investigating telomere length in major depressive disorder (MDD), a severe illness which shows signs of premature aging60,91,92. In particular, it has been described that telomere length in MDD subjects corresponds to a 10-year increase in biological age93 compared to healthy subjects. In line with this, increased abundance of short telomeres in patients with bipolar II disorder has also been described to correspond to a 13-year older biological age, again in agreement with increased risk for developing different diseases in these patients94. Interestingly, shorter telomeres are also associated with cognitive impairment in the elderly58.
In contrast to the detrimental factors causing accelerated telomere shortening, certain life habits (e.g. a diet rich in omega-3 fatty acids)81,95, as well as physical activity, exercise, and fitness, have been proposed to reduce telomere erosion and thus slow down the pace of aging96–98.
In addition to these various intrinsic and environmental factors, telomere length is also dictated by a genetic component. Earlier twin and family studies and a recent meta-analysis comprising nearly 20,000 subjects demonstrate that telomere length is highly heritable79,99–101. Whether the inheritance of telomere length correlates more strongly with paternal or maternal telomere length, however, is still debated102. Interestingly, in another twin study Christensen and colleagues reported that the perceived age in twins older than 70 years of age is a robust biomarker of aging which strongly correlates with telomere length. Moreover, within twin pairs, the twin with greater telomere length tends to look younger and live longer103.
Genetic models to understand the causal role of telomeres in disease and longevity
Firm experimental demonstration that critical telomere shortening is causative of aging was first achieved by generating mice deficient for telomerase. Mice deficient for TERC have progressively shorter telomeres over generations, leading to chromosome instability, developmental defects, premature aging phenotypes, and ultimately mouse infertility and premature death104–106. These mice show a decreased median and maximum lifespan already at the first generation107, and this decreased longevity and associated aging pathologies are anticipated with each mouse generation, thus demonstrating that telomere length in mice is causal of aging and longevity. Importantly, restoration of TERC expression in mice with inherited critically short telomeres is sufficient to prevent the phenotypes associated with short telomeres in these mice, including aplastic anemia, intestinal atrophy, and infertility, among others108,109. In agreement with these pioneer studies, genetic ablation of TERT was shown to have similar consequences on organismal aging and lifespan110,111. Furthermore, TERT reconstitution in late generation TERT-deficient mice also led to telomere elongation, lower DNA damage load, and reversal of degenerative phenotypes in these mice112. In line with these findings, lack of telomerase in lower vertebrates such as the zebrafish also causes premature aging which can be rescued by either telomerase restoration or inhibition of p53, which signals telomere damage113. Together, these findings demonstrate that short telomeres are causative of aging and that premature aging specifically induced by telomerase deficiency and short telomeres can be rescued by telomerase re-expression.
In line with mouse studies, a number of human syndromes were later described to be caused by germ line mutations in telomerase and shelterin genes, the so-called telomere syndromes47. As in the telomerase-deficient mouse model, the diseases associated with telomerase mutations are anticipated with increasing generations and involve a loss of the ability of tissues to regenerate, resulting in skin abnormalities, aplastic anemia, or pulmonary fibrosis46,47. These analogies between humans and mice highlight that telomere length as a genetic determinant of disease and longevity is a molecular mechanism conserved in these species.
However, definitive genetic demonstration that telomere length is also causative of physiological aging in normal individuals first came from telomerase overexpression studies in mice. In particular, mice with increased transgenic telomerase expression throughout their lifespans were able to maintain longer telomeres with aging, showed decreased molecular (i.e. lower DNA damage) and physiological biomarkers of aging, showed a delayed appearance of age-related pathologies (osteoporosis, metabolic decline, etc.), and showed a significant increase in organismal longevity. In particular, transgenic TERT overexpression in mice engineered to be cancer resistant resulted in decreased incidence of aging-related pathologies and a striking 40% extension of median survival compared to wild-type mice114. This study demonstrated for the first time in any organism the anti-aging activity of telomerase. Importantly, these findings led to the idea that potential therapeutic strategies based on transiently increased telomerase expression could also delay age-associated pathologies and increase longevity. This was first achieved by delivering TERT using non-integrative gene therapy vectors (adeno-associated vectors [AAVs]) into middle-aged and old mice, which resulted in transiently increased TERT expression in the majority of mouse tissues. Importantly, a single treatment with these vectors resulted in elongated telomeres in a range of organs, delayed age-associated pathologies, and significantly extended median and maximal lifespan in both age groups115. Moreover, these mice did not show increased cancer; instead, as seen in other age-related conditions, cancer was also delayed115. Thus telomere-based gene therapies using non-integrative vectors may represent a new therapeutic strategy to transiently activate TERT for the prevention or treatment of many different age-related pathologies (see below).
Telomeres and Telomerase as therapeutic targets
A substantial number of companies are now aiming to harness the knowledge that has been generated, unveiling the molecular mechanisms of aging in order to develop a new class of drugs to prevent and treat the major age-related diseases116. In this regard, telomerase overexpression studies in mice have been proof of principle that just modifying a single hallmark of aging, i.e. telomere shortening, this was sufficient to delay not one but many different age-associated pathologies in mice, including cognitive decline114,115. Indeed, the use of telomerase activation in delaying aging-associated conditions has spurred the interest of commercial enterprises. For instance, the low-potency telomerase activator TA-65 (a bio-active compound isolated from the herb Astragalus membranaceus) has been shown to lead to a mild increase in telomere length in mice117, zebra finches118, and humans119, and to improve several aging-related parameters in mice and humans117,119, although no increase in longevity has been reported in longitudinal mouse studies117. On the other hand, other natural compounds like sex hormones have been found to activate TERT at the transcriptional level120–122. In this regard, androgen therapy has been applied as a first-line treatment in aplastic anemia for decades with mixed success and without a clear understanding of the mechanism that underlies remission in some patients but not in others123,124. A recent study in mice which develop full-blown aplastic anemia provoked by short telomeres showed that androgen therapy rescues telomere attrition and subsequent death from aplastic anemia122, indicating that telomerase activation may indeed be a treatment option for diseases associated with flawed telomere maintenance (i.e. telomeropathies or telomere syndromes). However, potential off-target effects of compounds that activate TERT at a transcriptional level should be a concern. In particular, TA-65 has been shown to activate TERT through activation of mitogenic pathways that lead to the activation of the oncogene c-myc117,125 and thus may drive cancer. Interestingly, such off-target effects may be circumvented through direct delivery of TERT, such as by means of systemic gene therapy using non-integrative AAV vectors, which showed a significant delay of age-related pathologies in mice and increased longevity115. A recent study using fibroblasts in vitro also proposed delivery of the TERT mRNA as a way to activate telomerase126. However, it should be mentioned that strategies for telomerase activation, indirect or direct, have raised safety concerns due to the close correlation of most cancers and constitutive reactivation of endogenous telomerase. This highlights that, in addition to proof-of-concept studies in mice, the development of safe strategies for transient and controllable telomerase activation in humans should be a future goal.
In this regard, TERT gene therapy with AAVs is particularly attractive for TERT activation, since the non-integrative and replication-incompetent properties of AAVs allow for cell division-associated telomere elongation and subsequent loss of TERT expression as cells divide, thus restricting TERT expression to a few cell divisions. Thus, this strategy assures a transient and relatively genome-safe TERT activation. In contrast, the use of TERT mRNA currently lacks appropriate systems for in vivo delivery, and thus its use may be restricted to ex vivo applications.
It is likely that the first clinical use of a TERT-based therapy, such as the TERT gene therapy approach developed by us, will be for the treatment of the human telomere syndromes, including aplastic anemia and pulmonary fibrosis. However, this requires the development of appropriate preclinical models and the subsequent clinical trials in humans. In this regard, we have recently generated two mouse models which recapitulate the clinical features of aplastic anemia127 and pulmonary fibrosis128. The disease in both models is provoked by short and dysfunctional telomeres and thus these models provide a platform for further testing of TERT-based treatment strategies for the telomere syndromes.
Given that physiological aging is provoked, at least in part, by telomere shortening, a TERT gene therapy may be used not only for the prevention and treatment of telomere syndromes but also for the treatment of multiple age-related diseases. In this regard, short telomeres have been extensively associated with a higher risk for cardiovascular disease64,129,130. In support of a potential use of TERT activation in the treatment of age-related diseases, we demonstrated that TERT gene therapy can efficiently rescue mouse survival and heart scarring in a preclinical mouse model for heart failure upon induction of acute myocardial infarction131.
Collectively, experiments in cell and animal models provide proof of concept for the feasibility of telomerase activation approaches to counteract telomere shortening and its consequences (Figure 1). In particular, the successful use of telomerase gene therapy in animal models of aging and short telomere-related diseases paves the way for the development of therapeutic telomerase treatments in human aging and associated disease.
Figure 1. Telomeres in aging and disease.
Telomere shortening is a life-long process that is influenced by a number of intrinsic and environmental factors that either accelerate or slow down natural telomere attrition, which causes aging and the emergence of age-related diseases. The identification of telomere shortening as a driver of molecular aging has triggered the development of telomerase-based strategies to (re)elongate telomeres and thus to delay aging and associated disease. Abbreviations: AAV, adeno-associated vectors; TERT, telomerase reverse transcriptase.
Competing interests
Maria A. Blasco is co-founder of Life Length, a biotechnology company that commercializes measurement of telomere length for different applications.
Grant information
The author(s) declared that no grants were involved in supporting this work.
Faculty Opinions recommendedReferences
- 1.
de Lange T:
Protection of mammalian telomeres.
Oncogene.
2002; 21(4): 532–40. PubMed Abstract
| Publisher Full Text
- 2.
de Lange T:
Shelterin: the protein complex that shapes and safeguards human telomeres.
Genes Dev.
2005; 19(18): 2100–10. PubMed Abstract
| Publisher Full Text
- 3.
Martinez P, Thanasoula M, Carlos AR, et al.:
Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites.
Nat Cell Biol.
2010; 12(8): 768–80. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 4.
Martínez P, Blasco MA:
Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins.
Nat Rev Cancer.
2011; 11(3): 161–76. PubMed Abstract
| Publisher Full Text
- 5.
Martínez P, Gómez-López G, García F, et al.:
RAP1 protects from obesity through its extratelomeric role regulating gene expression.
Cell Rep.
2013; 3(6): 2059–74. PubMed Abstract
| Publisher Full Text
- 6.
Celli GB, de Lange T:
DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion.
Nat Cell Biol.
2005; 7(7): 712–8. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 7.
Martínez P, Thanasoula M, Muñoz P, et al.:
Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice.
Genes Dev.
2009; 23(17): 2060–75. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 8.
Tejera AM, Stagno d'Alcontres M, Thanasoula M, et al.:
TPP1 is required for TERT recruitment, telomere elongation during nuclear reprogramming, and normal skin development in mice.
Dev Cell.
2010; 18(5): 775–89. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 9.
Sfeir A, Kabir S, van Overbeek M, et al.:
Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal.
Science.
2010; 327(5973): 1657–61. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 10.
Kabir S, Hockemeyer D, de Lange T:
TALEN gene knockouts reveal no requirement for the conserved human shelterin protein Rap1 in telomere protection and length regulation.
Cell Rep.
2014; 9(4): 1273–80. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 11.
Griffith JD, Comeau L, Rosenfield S, et al.:
Mammalian telomeres end in a large duplex loop.
Cell.
1999; 97(4): 503–14. PubMed Abstract
| Publisher Full Text
- 12.
Doksani Y, Wu JY, de Lange T, et al.:
Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation.
Cell.
2013; 155(2): 345–56. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 13.
de Lange T:
How telomeres solve the end-protection problem.
Science.
2009; 326(5955): 948–52. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 14.
Watson JD:
Origin of concatemeric T7 DNA.
Nat New Biol.
1972; 239(94): 197–201. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 15.
Olovnikov AM:
A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon.
J Theor Biol.
1973; 41(1): 181–90. PubMed Abstract
| Publisher Full Text
- 16.
Harley CB, Futcher AB, Greider CW:
Telomeres shorten during ageing of human fibroblasts.
Nature.
1990; 345(6274): 458–60. PubMed Abstract
| Publisher Full Text
- 17.
Collado M, Blasco MA, Serrano M:
Cellular senescence in cancer and aging.
Cell.
2007; 130(2): 223–33. PubMed Abstract
| Publisher Full Text
- 18.
Hayflick L, Moorhead PS:
The serial cultivation of human diploid cell strains.
Exp Cell Res.
1961; 25: 585–621. PubMed Abstract
| Publisher Full Text
- 19.
Greider CW, Blackburn EH:
Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.
Cell.
1985; 43(2 Pt 1): 405–13. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 20.
Bodnar AG, Ouellette M, Frolkis M, et al.:
Extension of life-span by introduction of telomerase into normal human cells.
Science.
1998; 279(5349): 349–52. PubMed Abstract
| Publisher Full Text
- 21.
Morales CP, Holt SE, Ouellette M, et al.:
Absence of cancer-associated changes in human fibroblasts immortalized with telomerase.
Nat Genet.
1999; 21(1): 115–8. PubMed Abstract
| Publisher Full Text
- 22.
Jiang XR, Jimenez G, Chang E, et al.:
Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype.
Nat Genet.
1999; 21(1): 111–4. PubMed Abstract
| Publisher Full Text
- 23.
Schaetzlein S, Lucas-Hahn A, Lemme E, et al.:
Telomere length is reset during early mammalian embryogenesis.
Proc Natl Acad Sci U S A.
2004; 101(21): 8034–8. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 24.
Varela E, Schneider RP, Ortega S, et al.:
Different telomere-length dynamics at the inner cell mass versus established embryonic stem (ES) cells.
Proc Natl Acad Sci U S A.
2011; 108(37): 15207–12. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 25.
Blasco MA:
Telomere length, stem cells and aging.
Nat Chem Biol.
2007; 3(10): 640–9. PubMed Abstract
| Publisher Full Text
- 26.
López-Otín C, Blasco MA, Partridge L, et al.:
The hallmarks of aging.
Cell.
2013; 153(6): 1194–217. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 27.
Mitchell JR, Wood E, Collins K:
A telomerase component is defective in the human disease dyskeratosis congenita.
Nature.
1999; 402(6761): 551–5. PubMed Abstract
| Publisher Full Text
- 28.
Podlevsky JD, Chen JJ:
It all comes together at the ends: telomerase structure, function, and biogenesis.
Mutat Res.
2012; 730(1–2): 3–11. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 29.
Venteicher AS, Abreu EB, Meng Z, et al.:
A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.
Science.
2009; 323(5914): 644–8. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 30.
Azzalin CM, Reichenbach P, Khoriauli L, et al.:
Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends.
Science.
2007; 318(5851): 798–801. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 31.
López de Silanes I, Stagno d'Alcontres M, Blasco MA:
TERRA transcripts are bound by a complex array of RNA-binding proteins.
Nat Commun.
2010; 1: 33. PubMed Abstract
| Publisher Full Text
- 32.
Azzalin CM, Lingner J:
Telomere functions grounding on TERRA firma.
Trends Cell Biol.
2015; 25(1): 29–36. PubMed Abstract
| Publisher Full Text
- 33.
Wang C, Zhao L, Lu S:
Role of TERRA in the regulation of telomere length.
Int J Biol Sci.
2015; 11(3): 316–23. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 34.
Miyake Y, Nakamura M, Nabetani A, et al.:
RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway.
Mol Cell.
2009; 36(2): 193–206. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 35.
Surovtseva YV, Churikov D, Boltz KA, et al.:
Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes.
Mol Cell.
2009; 36(2): 207–18. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 36.
Crabbe L, Verdun RE, Haggblom CI, et al.:
Defective telomere lagging strand synthesis in cells lacking WRN helicase activity.
Science.
2004; 306(5703): 1951–3. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 37.
Li B, Reddy S, Comai L:
Sequence-specific processing of telomeric 3' overhangs by the Werner syndrome protein exonuclease activity.
Aging (Albany NY).
2009; 1(3): 289–302. PubMed Abstract
| Free Full Text
- 38.
Reddy S, Li B, Comai L:
Processing of human telomeres by the Werner syndrome protein.
Cell Cycle.
2010; 9(16): 3137–8. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 39.
Barefield C, Karlseder J:
The BLM helicase contributes to telomere maintenance through processing of late-replicating intermediate structures.
Nucleic Acids Res.
2012; 40(15): 7358–67. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 40.
Liu Y, Kao HI, Bambara RA:
Flap endonuclease 1: a central component of DNA metabolism.
Annu Rev Biochem.
2004; 73: 589–615. PubMed Abstract
| Publisher Full Text
- 41.
Sarek G, Vannier JB, Panier S, et al.:
TRF2 recruits RTEL1 to telomeres in S phase to promote t-loop unwinding.
Mol Cell.
2015; 57(4): 622–35. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 42.
Martínez P, Blasco MA:
Replicating through telomeres: a means to an end.
Trends Biochem Sci.
2015; 40(9): 504–15. PubMed Abstract
| Publisher Full Text
- 43.
Muñoz-Espín D, Serrano M:
Cellular senescence: from physiology to pathology.
Nat Rev Mol Cell Biol.
2014; 15(7): 482–96. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 44.
Flores I, Cayuela ML, Blasco MA:
Effects of telomerase and telomere length on epidermal stem cell behavior.
Science.
2005; 309(5738): 1253–6. PubMed Abstract
| Publisher Full Text
- 45.
Sharpless NE, DePinho RA:
How stem cells age and why this makes us grow old.
Nat Rev Mol Cell Biol.
2007; 8(9): 703–13. PubMed Abstract
| Publisher Full Text
- 46.
Calado RT, Young NS:
Telomere diseases.
N Engl J Med.
2009; 361(24): 2353–65. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 47.
Armanios M, Blackburn EH:
The telomere syndromes.
Nat Rev Genet.
2012; 13(10): 693–704. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 48.
Holohan B, Wright WE, Shay JW:
Cell biology of disease: Telomeropathies: an emerging spectrum disorder.
J Cell Biol.
2014; 205(3): 289–99. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 49.
Townsley DM, Dumitriu B, Young NS:
Bone marrow failure and the telomeropathies.
Blood.
2014; 124(18): 2775–83. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 50.
Counter CM, Avilion AA, LeFeuvre CE, et al.:
Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
EMBO J.
1992; 11(5): 1921–9. PubMed Abstract
| Free Full Text
- 51.
Chin L, Artandi SE, Shen Q, et al.:
p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis.
Cell.
1999; 97(4): 527–38. PubMed Abstract
| Publisher Full Text
- 52.
Sahin E, Colla S, Liesa M, et al.:
Telomere dysfunction induces metabolic and mitochondrial compromise.
Nature.
2011; 470(7334): 359–65. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 53.
Blasco MA:
The epigenetic regulation of mammalian telomeres.
Nat Rev Genet.
2007; 8(4): 299–309. PubMed Abstract
| Publisher Full Text
- 54.
Vera E, Canela A, Fraga MF, et al.:
Epigenetic regulation of telomeres in human cancer.
Oncogene.
2008; 27(54): 6817–33. PubMed Abstract
| Publisher Full Text
- 55.
Marión RM, Schotta G, Ortega S, et al.:
Suv4-20h abrogation enhances telomere elongation during reprogramming and confers a higher tumorigenic potential to iPS cells.
PLoS One.
2011; 6(10): e25680. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 56.
Fumagalli M, Rossiello F, Clerici M, et al.:
Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation.
Nat Cell Biol.
2012; 14(4): 355–65. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 57.
Hewitt G, Jurk D, Marques FD, et al.:
Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence.
Nat Commun.
2012; 3: 708. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 58.
Canela A, Vera E, Klatt P, et al.:
High-throughput telomere length quantification by FISH and its application to human population studies.
Proc Natl Acad Sci U S A.
2007; 104(13): 5300–5. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 59.
Epel ES, Blackburn EH, Lin J, et al.:
Accelerated telomere shortening in response to life stress.
Proc Natl Acad Sci U S A.
2004; 101(49): 17312–5. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 60.
Lin J, Epel E, Blackburn E:
Telomeres and lifestyle factors: roles in cellular aging.
Mutat Res.
2012; 730(1–2): 85–9. PubMed Abstract
| Publisher Full Text
- 61.
von Zglinicki T, Martin-Ruiz CM:
Telomeres as biomarkers for ageing and age-related diseases.
Curr Mol Med.
2005; 5(2): 197–203. PubMed Abstract
| Publisher Full Text
- 62.
Butler RN, Sprott R, Warner H, et al.:
Biomarkers of aging: from primitive organisms to humans.
J Gerontol A Biol Sci Med Sci.
2004; 59(6): B560–7. PubMed Abstract
| Publisher Full Text
- 63.
Simm A, Nass N, Bartling B, et al.:
Potential biomarkers of ageing.
Biol Chem.
2008; 389(3): 257–65. PubMed Abstract
| Publisher Full Text
- 64.
De Meyer T, Rietzschel ER, De Buyzere ML, et al.:
Telomere length and cardiovascular aging: the means to the ends?
Ageing Res Rev.
2011; 10(2): 297–303. PubMed Abstract
| Publisher Full Text
- 65.
Heidinger BJ, Blount JD, Boner W, et al.:
Telomere length in early life predicts lifespan.
Proc Natl Acad Sci U S A.
2012; 109(5): 1743–8. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 66.
Vera E, Bernardes de Jesus B, Foronda M, et al.:
The rate of increase of short telomeres predicts longevity in mammals.
Cell Rep.
2012; 2(4): 732–7. PubMed Abstract
| Publisher Full Text
- 67.
Moyzis RK, Buckingham JM, Cram LS, et al.:
A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.
Proc Natl Acad Sci U S A.
1988; 85(18): 6622–6. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 68.
Calado RT, Dumitriu B:
Telomere dynamics in mice and humans.
Semin Hematol.
2013; 50(2): 165–74. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 69.
Fick LJ, Fick GH, Li Z, et al.:
Telomere length correlates with life span of dog breeds.
Cell Rep.
2012; 2(6): 1530–6. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 70.
Barrett EL, Burke TA, Hammers M, et al.:
Telomere length and dynamics predict mortality in a wild longitudinal study.
Mol Ecol.
2013; 22(1): 249–59. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 71.
Boonekamp JJ, Mulder GA, Salomons HM, et al.:
Nestling telomere shortening, but not telomere length, reflects developmental stress and predicts survival in wild birds.
Proc Biol Sci.
2014; 281(1785): 20133287. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 72.
Tomás-Loba A, Bernardes de Jesus B, Mato JM, et al.:
A metabolic signature predicts biological age in mice.
Aging Cell.
2013; 12(1): 93–101. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 73.
Sanders JL, Newman AB:
Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither?
Epidemiol Rev.
2013; 35(1): 112–31. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 74.
Lapham K, Kvale MN, Lin J, et al.:
Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.
Genetics.
2015; 200(4): 1061–72. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 75.
Cawthon RM, Smith KR, O'Brien E, et al.:
Association between telomere length in blood and mortality in people aged 60 years or older.
Lancet.
2003; 361(9355): 393–5. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 76.
Martin-Ruiz CM, Gussekloo J, van Heemst D, et al.:
Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population-based study.
Aging Cell.
2005; 4(6): 287–90. PubMed Abstract
| Publisher Full Text
- 77.
Bischoff C, Petersen HC, Graakjaer J, et al.:
No association between telomere length and survival among the elderly and oldest old.
Epidemiology.
2006; 17(2): 190–4. PubMed Abstract
| Publisher Full Text
- 78.
Baird DM, Rowson J, Wynford-Thomas D, et al.:
Extensive allelic variation and ultrashort telomeres in senescent human cells.
Nat Genet.
2003; 33(2): 203–7. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 79.
Slagboom PE, Droog S, Boomsma DI:
Genetic determination of telomere size in humans: a twin study of three age groups.
Am J Hum Genet.
1994; 55(5): 876–82. PubMed Abstract
| Free Full Text
- 80.
Canela A, Klatt P, Blasco MA:
Telomere length analysis.
Methods Mol Biol.
2007; 371: 45–72. PubMed Abstract
| Publisher Full Text
- 81.
von Zglinicki T:
Oxidative stress shortens telomeres.
Trends Biochem Sci.
2002; 27(7): 339–44. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 82.
Valdes AM, Andrew T, Gardner JP, et al.:
Obesity, cigarette smoking, and telomere length in women.
Lancet.
2005; 366(9486): 662–4. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 83.
Strandberg TE, Saijonmaa O, Tilvis RS, et al.:
Association of telomere length in older men with mortality and midlife body mass index and smoking.
J Gerontol A Biol Sci Med Sci.
2011; 66(7): 815–20. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 84.
Verde Z, Reinoso-Barbero L, Chicharro L, et al.:
Effects of cigarette smoking and nicotine metabolite ratio on leukocyte telomere length.
Environ Res.
2015; 140: 488–94. PubMed Abstract
| Publisher Full Text
- 85.
Révész D, Milaneschi Y, Verhoeven JE, et al.:
Longitudinal Associations Between Metabolic Syndrome Components and Telomere Shortening.
J Clin Endocrinol Metab.
2015; 100(8): 3050–9. PubMed Abstract
| Publisher Full Text
- 86.
Strandberg TE, Strandberg AY, Saijonmaa O, et al.:
Association between alcohol consumption in healthy midlife and telomere length in older men. The Helsinki Businessmen Study.
Eur J Epidemiol.
2012; 27(10): 815–22. PubMed Abstract
| Publisher Full Text
- 87.
Müezzinler A, Mons U, Dieffenbach AK, et al.:
Smoking habits and leukocyte telomere length dynamics among older adults: Results from the ESTHER cohort.
Exp Gerontol.
2015; 70: 18–25. PubMed Abstract
| Publisher Full Text
- 88.
Wolkowitz OM, Mellon SH, Epel ES, et al.:
Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings.
PLoS One.
2011; 6(3): e17837. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 89.
Karabatsiakis A, Kolassa IT, Kolassa S, et al.:
Telomere shortening in leukocyte subpopulations in depression.
BMC Psychiatry.
2014; 14: 192. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 90.
O'Donovan A, Epel E, Lin J, et al.:
Childhood trauma associated with short leukocyte telomere length in posttraumatic stress disorder.
Biol Psychiatry.
2011; 70(5): 465–71. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 91.
Kinser PA, Lyon DE:
Major depressive disorder and measures of cellular aging: an integrative review.
Nurs Res Pract.
2013; 2013: 469070. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 92.
Lindqvist D, Epel ES, Mellon SH, et al.:
Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.
Neurosci Biobehav Rev.
2015; 55: 333–64. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 93.
Simon NM, Smoller JW, McNamara KL, et al.:
Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging.
Biol Psychiatry.
2006; 60(5): 432–5. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 94.
Elvsåshagen T, Vera E, Bøen E, et al.:
The load of short telomeres is increased and associated with lifetime number of depressive episodes in bipolar II disorder.
J Affect Disord.
2011; 135(1–3): 43–50. PubMed Abstract
| Publisher Full Text
- 95.
Farzaneh-Far R, Lin J, Epel ES, et al.:
Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease.
JAMA.
2010; 303(3): 250–7. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 96.
Werner C, Fürster T, Widmann T, et al.:
Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall.
Circulation.
2009; 120(24): 2438–47. PubMed Abstract
| Publisher Full Text
- 97.
Song Z, von Figura G, Liu Y, et al.:
Lifestyle impacts on the aging-associated expression of biomarkers of DNA damage and telomere dysfunction in human blood.
Aging Cell.
2010; 9(4): 607–15. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 98.
Soares-Miranda L, Imamura F, Siscovick D, et al.:
Physical Activity, Physical Fitness, and Leukocyte Telomere Length: The Cardiovascular Health Study.
Med Sci Sports Exerc.
2015; 47(12): 2525–34. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 99.
Bischoff C, Graakjaer J, Petersen HC, et al.:
The heritability of telomere length among the elderly and oldest-old.
Twin Res Hum Genet.
2005; 8(5): 433–9. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 100.
Andrew T, Aviv A, Falchi M, et al.:
Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs.
Am J Hum Genet.
2006; 78(3): 480–6. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 101.
Broer L, Codd V, Nyholt DR, et al.:
Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect.
Eur J Hum Genet.
2013; 21(10): 1163–8. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 102.
Eisenberg DT:
Inconsistent inheritance of telomere length (TL): is offspring TL more strongly correlated with maternal or paternal TL?
Eur J Hum Genet.
2014; 22(1): 8–9. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 103.
Christensen K, Thinggaard M, McGue M, et al.:
Perceived age as clinically useful biomarker of ageing: cohort study.
BMJ.
2009; 339: b5262. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 104.
Blasco MA, Lee HW, Hande MP, et al.:
Telomere shortening and tumor formation by mouse cells lacking telomerase RNA.
Cell.
1997; 91(1): 25–34. PubMed Abstract
| Publisher Full Text
- 105.
Herrera E, Samper E, Blasco MA:
Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube.
EMBO J.
1999; 18(5): 1172–81. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 106.
Lee HW, Blasco MA, Gottlieb GJ, et al.:
Essential role of mouse telomerase in highly proliferative organs.
Nature.
1998; 392(6676): 569–74. PubMed Abstract
| Publisher Full Text
- 107.
García-Cao I, García-Cao M, Tomás-Loba A, et al.:
Increased p53 activity does not accelerate telomere-driven ageing.
EMBO Rep.
2006; 7(5): 546–52. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 108.
Samper E, Flores JM, Blasco MA:
Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc-/- mice with short telomeres.
EMBO Rep.
2001; 2(9): 800–7. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 109.
Hemann MT, Strong MA, Hao LY, et al.:
The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability.
Cell.
2001; 107(1): 67–77. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 110.
Liu Y, Snow BE, Hande MP, et al.:
The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo.
Curr Biol.
2000; 10(22): 1459–62. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 111.
Erdmann N, Liu Y, Harrington L:
Distinct dosage requirements for the maintenance of long and short telomeres in mTert heterozygous mice.
Proc Natl Acad Sci U S A.
2004; 101(16): 6080–5. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 112.
Jaskelioff M, Muller FL, Paik JH, et al.:
Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice.
Nature.
2011; 469(7328): 102–6. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 113.
Anchelin M, Alcaraz-Pérez F, Martínez CM, et al.:
Premature aging in telomerase-deficient zebrafish.
Dis Model Mech.
2013; 6(5): 1101–12. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 114.
Tomás-Loba A, Flores I, Fernández-Marcos PJ, et al.:
Telomerase reverse transcriptase delays aging in cancer-resistant mice.
Cell.
2008; 135(4): 609–22. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 115.
Bernardes de Jesus B, Vera E, Schneeberger K, et al.:
Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer.
EMBO Mol Med.
2012; 4(8): 691–704. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 116.
Scott CT, DeFrancesco L:
Selling long life.
Nat Biotechnol.
2015; 33(1): 31–40. PubMed Abstract
| Publisher Full Text
- 117.
Bernardes de Jesus B, Schneeberger K, Vera E, et al.:
The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence.
Aging Cell.
2011; 10(4): 604–21. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 118.
Reichert S, Bize P, Arrivé M, et al.:
Experimental increase in telomere length leads to faster feather regeneration.
Exp Gerontol.
2014; 52: 36–8. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 119.
Harley CB, Liu W, Blasco M, et al.:
A natural product telomerase activator as part of a health maintenance program.
Rejuvenation Res.
2011; 14(1): 45–56. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 120.
Kyo S, Takakura M, Kanaya T, et al.:
Estrogen activates telomerase.
Cancer Res.
1999; 59(23): 5917–21. PubMed Abstract
- 121.
Calado RT, Yewdell WT, Wilkerson KL, et al.:
Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells.
Blood.
2009; 114(11): 2236–43. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 122.
Bär C, Huber N, Beier F, et al.:
Therapeutic effect of androgen therapy in a mouse model of aplastic anemia produced by short telomeres.
Haematologica.
2015; 100(10): 1267–74. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 123.
Shahidi NT, Diamond LK:
Testosterone-induced remission in aplastic anemia of both acquired and congenital types. Further observations in 24 cases.
N Engl J Med.
1961; 264: 953–67. PubMed Abstract
| Publisher Full Text
- 124.
Jaime-Pérez JC, Colunga-Pedraza PR, Gómez-Ramírez CD, et al.:
Danazol as first-line therapy for aplastic anemia.
Ann Hematol.
2011; 90(5): 523–7. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 125.
Molgora B, Bateman R, Sweeney G, et al.:
Functional assessment of pharmacological telomerase activators in human T cells.
Cells.
2013; 2(1): 57–66. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 126.
Ramunas J, Yakubov E, Brady JJ, et al.:
Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells.
FASEB J.
2015; 29(5): 1930–9. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 127.
Beier F, Foronda M, Martinez P, et al.:
Conditional TRF1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of dyskeratosis congenita.
Blood.
2012; 120(15): 2990–3000. PubMed Abstract
| Publisher Full Text
| Free Full Text
- 128.
Povedano JM, Martinez P, Flores JM, et al.:
Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction.
Cell Rep.
2015; 12(2): 286–99. PubMed Abstract
| Publisher Full Text
| Faculty Opinions Recommendation
- 129.
Fyhrquist F, Saijonmaa O, Strandberg T:
The roles of senescence and telomere shortening in cardiovascular disease.
Nat Rev Cardiol.
2013; 10(5): 274–83. PubMed Abstract
| Publisher Full Text
- 130.
Haycock PC, Heydon EE, Kaptoge S, et al.:
Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis.
BMJ.
2014; 349: g4227. PubMed Abstract
| Publisher Full Text
| Free Full Text
| Faculty Opinions Recommendation
- 131.
Bär C, Bernardes de Jesus B, Serrano R, et al.:
Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction.
Nat Commun.
2014; 5: 5863. PubMed Abstract
| Publisher Full Text
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