Telomere shortening in leukocyte subpopulations from baboons

Baerlocher, Gabriela M.; Mak, Jennifer Sze Man; Röth, Alexander; Rice, Karen; Lansdorp, Peter M.

doi:10.1189/jlb.0702361

Cited by 37 publications

(32 citation statements)

References 53 publications

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“…A similar rate of shortening is seen in PBMCs from chimpanzees (Feng et al 1999), and these rates are similar to that seen in humans. Telomere shortening also occurs with age (between 0.2 and 26.5 years) in leukocytes of baboons (Papio hamadryas cynocephalus), and in general, cell type-specific telomere kinetics in baboons are remarkably similar to those observed in humans (Baerlocher et al 2003).…”

Section: Primatesmentioning

confidence: 81%

Telomeres and Telomerase Biology in Vertebrates: Progress Towards a Non-Human Model for Replicative Senescence and Ageing

Davis

Kipling

2005

Biogerontology

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Studies on telomere and telomerase biology are fundamental to the understanding of human ageing and age-related diseases such as cancer. However, human studies of whole body ageing are hampered by the lack of suitable fully reflective animal model systems, the wild-type mouse model being unsuitable due to differences in telomere biology. Here we summarise recent data on the biology of telomeres, telomerase, and the tumour suppressor protein p53 in various animals, and examine their possible roles in replicative senescence, ageing, and tumourigenesis. The advantages and disadvantages of various animals as model systems for whole body ageing in humans are discussed.

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Section: Primatesmentioning

confidence: 81%

Telomeres and Telomerase Biology in Vertebrates: Progress Towards a Non-Human Model for Replicative Senescence and Ageing

Davis

Kipling

2005

Biogerontology

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Section: Telomere-length Datamentioning

confidence: 99%

“…Granulocyte telomere lengths were measured for 132 baboons aged between 0.92 and 24 years. 25 Granulocytes were used because they are readily obtained and purified to homogeneity and are short-lived (circulation life spans, Ͻ 5-10 hours).T-cell culturing and computational techniques for 5 rhesus macaques (2-9 measurements per animal) were identical to those of baboons. 36 Total white blood cell telomere lengths were measured for 14 rhesus macaques aged between 2.8 and 15.3 years.…”

mentioning

confidence: 99%

Hematopoietic stem-cell behavior in nonhuman primates

Shepherd

Kiem

Lansdorp

et al. 2007

Blood

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Little is known about the behavior of hematopoietic stem cells (HSCs) in primates because direct observations and competitive-repopulation assays are not feasible. Therefore, we used 2 different and independent experimental strategies, the tracking of transgene expression after retroviral-mediated gene transfer (N ‫؍‬ 11 baboons; N ‫؍‬ 7 rhesus macaques) and quantitation of the average telomere length of granulocytes (N ‫؍‬ 132 baboons; N ‫؍‬ 14 macaques), together with stochastic methods, to study HSC kinetics in vivo. The average replication rate for baboon HSCs is once per 36 weeks according to gene-marking analyses and once per 23 weeks according to telomere-shortening analyses. Comparable results were derived from the macaque data. These rates are substantially slower than the average replication rates previously reported for HSCs in mice (once per 2.5 weeks) and cats (once per 8.3 weeks). Because baboons and macaques live for 25 to 45 years, much longer than mice (ϳ2 years) and cats (12-18 years), we can compute that HSCs undergo a relatively constant number (ϳ80-200) of lifetime replications. Thus, our data suggest that the self-renewal capacity of mammalian stem cells in vivo is defined and evolutionarily conserved. IntroductionHematopoiesis is the ordered process by which hematopoietic stem cells (HSCs) proliferate and differentiate into mature blood cells. Through replication and differentiation, HSCs generate clones of progenitors, precursors, and mature cells, which support hematopoiesis throughout an animal's life. HSCs cannot be directly observed and are generally defined and identified by their function (their ability to reconstitute and maintain hematopoiesis).The most informative experimental approach for studying HSC kinetics is limiting-dilution competitive-repopulation experiments. Small numbers of cells with distinguishable phenotypes are transplanted into a recipient animal in which hematopoiesis has been ablated. After the HSCs engraft and restore blood cell production, the percentage of marrow progenitor cells or blood granulocytes of each phenotype is tracked over time, because this reflects the phenotype of contributing (differentiating) HSC clones. 1,2 Using such data, the frequency of HSCs in mice and cats was estimated, as were their average replication and differentiation rates. [3][4][5] Importantly, the estimated frequency of HSCs in mice derived with stochastic analyses was similar to frequencies estimated with independent methods. [6][7][8][9] In addition, the results from transplantation studies overlapped the results from studies of unperturbed hematopoiesis, including 5-bromodeoxyuridine (BrdU)-labeling experiments. 6,9,10 Given the significant differences in estimates of the frequency of HSCs (number of HSCs/number of nucleated marrow cells; 4-8/10 5 vs. 6/10 7 ) and the average HSC-replication rate (once/2.5 weeks vs once/8-10 weeks) between mice and cats, we hypothesized that underlying biologic principles might explain these discrepancies. For example, our data and addit...

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“…Interestingly, similar kinetics of telomere shortening were observed over the age range of 0.2-26.5 years in baboons. 89 Recently, by using stochastic simulation of replication rates of HSC in vivo based on telomere length kinetics, Shepherd et al 90 demonstrated that HSC turnover rates differ quite substantially between vertebrates, ranging from once per 2.5 weeks in mice to once per 8-10 weeks in cats to once per 45 weeks in humans.…”

Section: Kinetics Of Telomere Shortening In Sub-populations Of Human mentioning

confidence: 99%

Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover

Brümmendorf

Balabanov

2006

Leukemia

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Telomeres both reflect and limit the replicative lifespan of normal somatic cells. Immature sub-populations of human CD34 þ 38À hematopoietic stem cell (HSC) can be identified in vitro based on their growth kinetics and telomere length. Fluorescence in situ hybridization and flow cytometry (flow-FISH) has been used to characterize telomere length dynamics as a surrogate marker for HSC turnover in vivo. Investigations in normal steady-state hematopoiesis provided the basis for follow-up studies in model scenarios characterized by increased HSC turnover. Disorders with underlying malignant transformation of HSC (e.g., chronic myeloid leukemia (CML)) can be discriminated from disease states with increased HSC turnover rates secondary to depletion of the stem cell compartment, for example, as in defined bone marrow failure syndromes. In some of these model scenarios, the degree of telomere shortening can be correlated with disease duration, disease stage and severity as well as with response to diseasemodifying treatment strategies. Whether increased telomere shortening represents a causal link between HSC turnover, replicative senescence and/or the induction of genetic instability in acquired HSC disorders remains to be shown. However, data from congenital disorders, like dyskeratosis congenita (DKC), suggest that disturbed telomere maintenance may play a role for replicative exhaustion of the HSC pool in vivo.

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Telomere shortening in leukocyte subpopulations from baboons

Cited by 37 publications

References 53 publications

Telomeres and Telomerase Biology in Vertebrates: Progress Towards a Non-Human Model for Replicative Senescence and Ageing

Telomeres and Telomerase Biology in Vertebrates: Progress Towards a Non-Human Model for Replicative Senescence and Ageing

Hematopoietic stem-cell behavior in nonhuman primates

Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover

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