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Telomere attrition due to infection.

Ilmonen P, Kotrschal A, Penn DJ - PLoS ONE (2008)

Bottom Line: Our results show that repeated Salmonella infections cause telomere attrition in WBCs, and particularly for males, which appeared less disease resistant than females.Interestingly, we also found that individuals having long WBC telomeres at early age were relatively disease resistant during later life.Finally, we found evidence that more rapid telomere attrition increases mortality risk, although this trend was not significant.

View Article: PubMed Central - PubMed

Affiliation: Konrad Lorenz Institute for Ethology, Austrian Academy of Sciences, Vienna, Austria. p.ilmonen@klivv.oeaw.ac.at

ABSTRACT

Background: Telomeres--the terminal caps of chromosomes--become shorter as individuals age, and there is much interest in determining what causes telomere attrition since this process may play a role in biological aging. The leading hypothesis is that telomere attrition is due to inflammation, exposure to infectious agents, and other types of oxidative stress, which damage telomeres and impair their repair mechanisms. Several lines of evidence support this hypothesis, including observational findings that people exposed to infectious diseases have shorter telomeres. Experimental tests are still needed, however, to distinguish whether infectious diseases actually cause telomere attrition or whether telomere attrition increases susceptibility to infection. Experiments are also needed to determine whether telomere erosion reduces longevity.

Methodology/principal findings: We experimentally tested whether repeated exposure to an infectious agent, Salmonella enterica, causes telomere attrition in wild-derived house mice (Mus musculus musculus). We repeatedly infected mice with a genetically diverse cocktail of five different S. enterica strains over seven months, and compared changes in telomere length with sham-infected sibling controls. We measured changes in telomere length of white blood cells (WBC) after five infections using a real-time PCR method. Our results show that repeated Salmonella infections cause telomere attrition in WBCs, and particularly for males, which appeared less disease resistant than females. Interestingly, we also found that individuals having long WBC telomeres at early age were relatively disease resistant during later life. Finally, we found evidence that more rapid telomere attrition increases mortality risk, although this trend was not significant.

Conclusions/significance: Our results indicate that infectious diseases can cause telomere attrition, and support the idea that telomere length could provide a molecular biomarker for assessing exposure and ability to cope with infectious diseases.

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Related in: MedlinePlus

Initial telomere length and Salmonella load at termination.Relative telomere lengths (T/S ratio) at the start in WBCs from females (indicated with filled circles; N = 10) and males (open circles; N = 7) predicted Salmonella loads (log10 colony forming units/ml of spleen) at the end of the experiment.
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pone-0002143-g003: Initial telomere length and Salmonella load at termination.Relative telomere lengths (T/S ratio) at the start in WBCs from females (indicated with filled circles; N = 10) and males (open circles; N = 7) predicted Salmonella loads (log10 colony forming units/ml of spleen) at the end of the experiment.

Mentions: Interestingly, we also found evidence that telomere length influences susceptibility to infectious disease. The mice that cleared Salmonella by the termination of the experiment, and hence were most resistant, had significantly longer WBC telomeres at the beginning than those that were still infected (Mann-Whitney U-test, U = 8.00, N = 17, P = 0.008; Fig. 2). Furthermore, individuals with relatively long telomeres at the beginning of the experiment had lower bacterial loads at termination (Spearman rank correlation, rs = −0.72, N = 17, P = 0.0006; Fig. 3). These results suggest that individuals with long WBC telomeres at early age are more resistant to Salmonella, perhaps due to a higher proliferation capacity of leukocytes that increases efficiency of fighting infection [30], or perhaps telomere length reflects a more general aspect of individual quality [31] or ability to cope with stress [5], [6].


Telomere attrition due to infection.

Ilmonen P, Kotrschal A, Penn DJ - PLoS ONE (2008)

Initial telomere length and Salmonella load at termination.Relative telomere lengths (T/S ratio) at the start in WBCs from females (indicated with filled circles; N = 10) and males (open circles; N = 7) predicted Salmonella loads (log10 colony forming units/ml of spleen) at the end of the experiment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2366059&req=5

pone-0002143-g003: Initial telomere length and Salmonella load at termination.Relative telomere lengths (T/S ratio) at the start in WBCs from females (indicated with filled circles; N = 10) and males (open circles; N = 7) predicted Salmonella loads (log10 colony forming units/ml of spleen) at the end of the experiment.
Mentions: Interestingly, we also found evidence that telomere length influences susceptibility to infectious disease. The mice that cleared Salmonella by the termination of the experiment, and hence were most resistant, had significantly longer WBC telomeres at the beginning than those that were still infected (Mann-Whitney U-test, U = 8.00, N = 17, P = 0.008; Fig. 2). Furthermore, individuals with relatively long telomeres at the beginning of the experiment had lower bacterial loads at termination (Spearman rank correlation, rs = −0.72, N = 17, P = 0.0006; Fig. 3). These results suggest that individuals with long WBC telomeres at early age are more resistant to Salmonella, perhaps due to a higher proliferation capacity of leukocytes that increases efficiency of fighting infection [30], or perhaps telomere length reflects a more general aspect of individual quality [31] or ability to cope with stress [5], [6].

Bottom Line: Our results show that repeated Salmonella infections cause telomere attrition in WBCs, and particularly for males, which appeared less disease resistant than females.Interestingly, we also found that individuals having long WBC telomeres at early age were relatively disease resistant during later life.Finally, we found evidence that more rapid telomere attrition increases mortality risk, although this trend was not significant.

View Article: PubMed Central - PubMed

Affiliation: Konrad Lorenz Institute for Ethology, Austrian Academy of Sciences, Vienna, Austria. p.ilmonen@klivv.oeaw.ac.at

ABSTRACT

Background: Telomeres--the terminal caps of chromosomes--become shorter as individuals age, and there is much interest in determining what causes telomere attrition since this process may play a role in biological aging. The leading hypothesis is that telomere attrition is due to inflammation, exposure to infectious agents, and other types of oxidative stress, which damage telomeres and impair their repair mechanisms. Several lines of evidence support this hypothesis, including observational findings that people exposed to infectious diseases have shorter telomeres. Experimental tests are still needed, however, to distinguish whether infectious diseases actually cause telomere attrition or whether telomere attrition increases susceptibility to infection. Experiments are also needed to determine whether telomere erosion reduces longevity.

Methodology/principal findings: We experimentally tested whether repeated exposure to an infectious agent, Salmonella enterica, causes telomere attrition in wild-derived house mice (Mus musculus musculus). We repeatedly infected mice with a genetically diverse cocktail of five different S. enterica strains over seven months, and compared changes in telomere length with sham-infected sibling controls. We measured changes in telomere length of white blood cells (WBC) after five infections using a real-time PCR method. Our results show that repeated Salmonella infections cause telomere attrition in WBCs, and particularly for males, which appeared less disease resistant than females. Interestingly, we also found that individuals having long WBC telomeres at early age were relatively disease resistant during later life. Finally, we found evidence that more rapid telomere attrition increases mortality risk, although this trend was not significant.

Conclusions/significance: Our results indicate that infectious diseases can cause telomere attrition, and support the idea that telomere length could provide a molecular biomarker for assessing exposure and ability to cope with infectious diseases.

Show MeSH
Related in: MedlinePlus