Abstract:Several studies have shown associations between shorter telomere length in blood and weakened immune function, susceptibility to infections, and increased risk of morbidity and mortality. Recently, we have shown that malaria accelerates telomere attrition in blood cells and shortens lifespan in birds. However, the impact of infections on telomere attrition in different body tissues within an individual is unknown. Here, we tested whether malarial infection leads to parallel telomere shortening in blood and tis… Show more
“…In comparison, smoking is thought to cause an estimated 3 bp/year steeper decline in BTL with age (Benetos et al, 2013). Recent evidence from experimental infection of a bird with avian malaria showed TL shortening in not just blood, but also liver, lung, spleen, heart, kidney and brain (Asghar et al, 2016). BTL is a marker of the TL of hematopoietic stem cells and shorter hematopoietic stem cell TL could have important effects on leukocyte and erythrocyte production.…”
Section: Discussionmentioning
confidence: 99%
“…In mice, and birds experimental infections have been shown to cause shortened TLs (Ilmonen et al, 2008; Asghar et al, 2015; Asghar et al, 2016). In humans, studies examining associations between infectious diseases and blood or lymphocyte TL have primarily been limited to adults in clinical contexts from high income countries.…”
Objectives
Telomeres are repetitive DNA at chromosomes ends that shorten with age due to cellular replication and oxidative stress. As telomeres shorten, this can eventually place limits on cell replication and contribute to senescence. Infections are common during early development and activate cellular immune responses that involve clonal expansion and oxidative stress. As such, a high infectious disease burden might shorten blood telomere length (BTL) and accelerate the pace of immune senescence.
Methods
To test this, BTL measured in young adults (21.7 ± 0.3 years old) from the Philippines (N=1,759) were linked to prospectively collected early life data on infectious burden.
Results
As predicted, increased early life diarrheal prevalence was associated with shorter adult BTL. The association was most marked for infections experienced from 6–12 months, which corresponds with weaning and maximal diarrheal burden. A standard deviation increase in infections at 6–12 m predicts a 45 bp decrease in BTL, equivalent to 3.3 years of adult telomeric aging in this population. Contrary to expectations, breastfeeding duration was not associated with BTL, nor did effects vary by sex.
Conclusions
These findings show that infancy diarrheal disease predicts a marker of cellular aging in adult immune cells. These findings suggest that early life infectious burden may influence late life health, or alternatively, that short TL in early life increases infectious disease susceptibility.
“…In comparison, smoking is thought to cause an estimated 3 bp/year steeper decline in BTL with age (Benetos et al, 2013). Recent evidence from experimental infection of a bird with avian malaria showed TL shortening in not just blood, but also liver, lung, spleen, heart, kidney and brain (Asghar et al, 2016). BTL is a marker of the TL of hematopoietic stem cells and shorter hematopoietic stem cell TL could have important effects on leukocyte and erythrocyte production.…”
Section: Discussionmentioning
confidence: 99%
“…In mice, and birds experimental infections have been shown to cause shortened TLs (Ilmonen et al, 2008; Asghar et al, 2015; Asghar et al, 2016). In humans, studies examining associations between infectious diseases and blood or lymphocyte TL have primarily been limited to adults in clinical contexts from high income countries.…”
Objectives
Telomeres are repetitive DNA at chromosomes ends that shorten with age due to cellular replication and oxidative stress. As telomeres shorten, this can eventually place limits on cell replication and contribute to senescence. Infections are common during early development and activate cellular immune responses that involve clonal expansion and oxidative stress. As such, a high infectious disease burden might shorten blood telomere length (BTL) and accelerate the pace of immune senescence.
Methods
To test this, BTL measured in young adults (21.7 ± 0.3 years old) from the Philippines (N=1,759) were linked to prospectively collected early life data on infectious burden.
Results
As predicted, increased early life diarrheal prevalence was associated with shorter adult BTL. The association was most marked for infections experienced from 6–12 months, which corresponds with weaning and maximal diarrheal burden. A standard deviation increase in infections at 6–12 m predicts a 45 bp decrease in BTL, equivalent to 3.3 years of adult telomeric aging in this population. Contrary to expectations, breastfeeding duration was not associated with BTL, nor did effects vary by sex.
Conclusions
These findings show that infancy diarrheal disease predicts a marker of cellular aging in adult immune cells. These findings suggest that early life infectious burden may influence late life health, or alternatively, that short TL in early life increases infectious disease susceptibility.
“…and the chicken(Li et al, 2014). Furthermore, since blood has been shown to reflect changes occurring in other tissues(Asghar et al, 2016;Watson, Videvall, Andersson, & Isaksson, 2017), the observed changes might not only suggest a wide window of sensitivity to environmentally induced epigenetic changes for this particular tissue, but at the whole-organism level. The occurrence of genome-wide changes in methylation in blood throughout postnatal development is of foremost ecological relevance, as it suggests a wide window during which environmentally induced epigenetic modifications could occur.…”
DNA methylation could shape phenotypic responses to environmental cues and underlie developmental plasticity. Environmentally induced changes in DNA methylation during development can give rise to stable phenotypic traits and thus affect fitness. In the laboratory, it has been shown that the vertebrate methylome undergoes dynamic reprogramming during development, creating a critical window for environmentally induced epigenetic modifications. Studies of DNA methylation in the wild are lacking, yet are essential for understanding how genes and the environment interact to affect phenotypic development and ultimately fitness. Furthermore, our knowledge of the establishment of methylation patterns during development in birds is limited. We quantified genome‐wide DNA methylation at various stages of embryonic and postnatal development in an altricial passerine bird, the great tit Parus major. While, there was no change in global DNA methylation in embryonic tissue during the second half of embryonic development, a twofold increase in DNA methylation in blood occurred between 6 and 15 days posthatch. Though not directly comparable, DNA methylation levels were higher in the blood of nestlings compared with embryonic tissue at any stage of prenatal development. This provides the first evidence that DNA methylation undergoes global change during development in a wild bird, supporting the hypothesis that methylation mediates phenotypic development. Furthermore, the plasticity of DNA methylation demonstrated during late postnatal development, in the present study, suggests a wide window during which DNA methylation could be sensitive to environmental influences. This is particularly important for our understanding of the mechanisms by which early‐life conditions influence later‐life performance. While, we found no evidence for differences in genome‐wide methylation in relation to habitat of origin, environmental variation is likely to be an important driver of variation in methylation at specific loci.
“…Both Plasmodium infection alone and infection intensity (i.e. parasitaemia) of Plasmodium have been previously associated with increased oxidative damage to plasma metabolites and to DNA [2, 34, 35]. Taken together, these results show that the oxidative stress phenomenon and its interplay with infection are complex and therefore need to be studied using a range of markers that capture different aspects of the oxidative process.Fig.…”
Section: Introductionmentioning
confidence: 73%
“…The higher pro-oxidant release by mitochondria in infected individuals suggests that Plasmodium parasites impose a cost on their host in terms of an enhanced energy requirement resulting in increased oxidative stress. This may have further important consequences in terms of oxidative damage leading to telomere shortening in red blood cells [2] but also in other tissues [35] potentially triggering a faster ageing associated with malaria disease.…”
Background
Plasmodium parasites may affect the oxidative status of their hosts, defined as the balance of pro-oxidant compounds and antioxidant defences in an organism. An increased energy requirement, the activation of immune functions or the parasite itself may lead to a higher production of pro-oxidants and/or an antioxidant depletion resulting in a higher oxidative stress and associated damage in infected individuals. Relatively little is known about the mechanisms underlying oxidative processes at play during host-Plasmodium interaction in the wild.MethodsThe effect of Plasmodium infection on host oxidative status was investigated in wild populations of breeding great tits, Parus major, naturally infected by Plasmodium spp. When chicks were 14 days old, the parents were blood-sampled to measure four complementary oxidative status markers: pro-oxidant production as mitochondrial superoxide production in red blood cells (RBC), antioxidant defences as plasma antioxidant capacity and oxidative damage as reactive oxygen metabolites in the plasma and RBC membrane resistance to oxidative attack.Results
Plasmodium-infected individuals produced more pro-oxidants compared to uninfected ones and pro-oxidant production positively correlated to infection intensity. There was also a conditional effect of reproductive effort on oxidative damage depending on Plasmodium infection status. There was no direct effect of infection on oxidative damage and no effect on antioxidant defences.ConclusionsThe results suggest that Plasmodium parasites may impose a cost in terms of increased oxidative stress possibly mediated via a higher energy requirement in infected hosts. This further suggests that Plasmodium parasites may modify host life history traits via an induction of oxidative stress. This study highlights that measuring several complementary oxidative status markers may enable to capture oxidative processes at play during host-Plasmodium interactions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1579-9) contains supplementary material, which is available to authorized users.
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