Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes

Lin, Jue; Cheon, Joshua; Brown, Rashida; Coccia, Michael; Puterman, Eli; Aschbacher, Kirstin; Sinclair, Elizabeth; Epel, Elissa S.; Blackburn, Elizabeth H.

doi:10.1155/2016/5371050

Cited by 96 publications

(71 citation statements)

References 45 publications

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“…A limitation of our study is that we are not able to pinpoint whether malaria has a synchronized effect on cellular aging markers in all cell types or whether there are specific effects on certain cell subtypes. Nonetheless, telomere length measured in total peripheral blood mononuclear cells (PBMCs) has been shown to be highly correlated to different cell subtypes, and to be highly synchronized in monocytes, T cells, and B cells in healthy individuals (Lin et al., 2016). Furthermore, it has also been shown that there is a synchrony in telomere length and telomere loss in adult mammals and humans (Daniali et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

Cellular aging dynamics after acute malaria infection: A 12‐month longitudinal study

et al. 2017

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SummaryAccelerated cellular aging and reduced lifespan have recently been shown in birds chronically infected with malaria parasites. Whether malaria infection also affects cellular aging in humans has not been reported. Here, we assessed the effect of a single acute Plasmodium falciparum malaria infection on cellular aging dynamics in travelers prospectively followed over one year in Sweden. DNA and RNA were extracted from venous blood collected at the time of admission and repeatedly up to one year. Telomere length was measured using real‐time quantitative PCR, while telomerase activity and CDKN2A expression were measured by reverse transcriptase (RT)–qPCR. Our results show that acute malaria infection affects cellular aging as reflected by elevated levels of CDKN2A expression, lower telomerase activity, and substantial telomere shortening during the first three months postinfection. After that CDKN2A expression declined, telomerase activity increased and telomere length was gradually restored over one year, reflecting that cellular aging was reversed. These findings demonstrate that malaria infection affects cellular aging and the underlying cellular mechanism by which pathogens can affect host cellular aging and longevity need to be elucidated. Our results urge the need to investigate whether repeated malaria infections have more pronounced and long‐lasting effects on cellular aging and lifespan (similarly to what was observed in birds) in populations living in malaria endemic areas.

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Section: Discussionmentioning

confidence: 99%

Cellular aging dynamics after acute malaria infection: A 12‐month longitudinal study

et al. 2017

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“…This variability may be due to the fact that we did not differentiate between lymphocyte types. Indeed, telomere dynamics differ not only among leucocyte types (as we considered here) but also among lymphocyte types (Weng, ; Lin, Cheon, & Brown, ). However, in Soay sheep, this methodological refinement led to weaker relationships between lymphocyte types and telomere length than the simple correlation between lymphocyte proportion and telomere length (Watson et al., ).…”

Section: Discussionmentioning

confidence: 99%

Mind the cell: Seasonal variation in telomere length mirrors changes in leucocyte profile

et al. 2017

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Leucocytes are typically considered as a whole in studies examining telomere dynamics in mammals. Such an approach may be precarious, as leucocytes represent the only nucleated blood cells in mammals, their composition varies temporally, and telomere length differs between leucocyte types. To highlight this limitation, we examined here whether seasonal variation in leucocyte composition was related to variation in telomere length in free-ranging mandrills (Mandrilllus sphinx). We found that the leucocyte profile of mandrills varied seasonally, with lower lymphocyte proportion being observed during the long dry season presumably because of the combined effects of high nematode infection and stress at that time of the year. Interestingly, this low lymphocyte proportion during the long dry season was associated with shorter telomeres. Accordingly, based on longitudinal data, we found that seasonal changes in lymphocyte proportion were reflected by corresponding seasonal variation in telomere length. Overall, these results suggest that variation in lymphocyte proportion in blood can significantly affect telomere measurements in mammals. However, lymphocyte proportion did not entirely explain variation in telomere length. For instance, a lower lymphocyte proportion with age could not fully explain shorter telomeres in older individuals. Overall, our results show that telomere length and leucocyte profile are strongly although imperfectly intertwined, which may obscure the relationship between telomere dynamics and ageing processes in mammals.

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“…For instance, studies on HIV elucidated the link between chronic infection and telomere attrition in CD4 + and CD8 + T cells 23 24. The replicative senescence of T lymphocytes is not limited to HIV since it is broadly investigated in association with malignancies,25 autoimmune disorders26 and environmental mediators 27 28. In autoimmune diseases, telomere erosion in lymphocytes has been less well delineated.…”

Section: Discussionmentioning

confidence: 99%

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout

et al. 2017

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Vazirpanah, N. et al. (2017) Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout. Annals of the Rheumatic Diseases, 76(7), pp. 1309-1315. (doi:10.1136/annrheumdis-2016-210538) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/139064/ Abstract:Aim and background: Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout.Methods: We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New-Zealand. Subsequently, we investigated the effect of cardiovascular disease on TL of all participants. Also, we measured TL of CD4 + and CD8 + T lymphocytes, B lymphocytes, monocytes, natural killer (NK) cells and plasmacytoid dendritic cells (pDCs). Additionally, we assessed the potential temporal difference in TL and telomerase activity.Results: TL in PBMCs of healthy donors decreased over time reflecting normal ageing. Patients with gout demonstrated shorter telomeres (P=0.001, R 2 =0.01873). In fact, the extent of telomere erosion in patients with gout was higher at any age as compared to healthy counterparts at any age (P<0.0001, R 2 =0.02847). Patients with gout with cardiovascular disease had the shortest telomeres and TL was an independent risk factor for cardiovascular disease in patients with gout (P=0.001). TL was inversely associated with the number of gouty flares (P=0.005).Conclusions: Patients with gout have shorter telomeres than healthy participants, reflecting increased cellular senescence. Telomere shortening was associated with the number of flares, and with cardiovascular disease in people with gout.

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Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes

Cited by 96 publications

References 45 publications

Cellular aging dynamics after acute malaria infection: A 12‐month longitudinal study

Cellular aging dynamics after acute malaria infection: A 12‐month longitudinal study

Mind the cell: Seasonal variation in telomere length mirrors changes in leucocyte profile

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout

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