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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

The consequences of infection on telomere length.Change of telomere length (mean±s.e.m.) of WBCs from sham-infected controls (white bars) versus infected mice that still harboured Salmonella at termination (grey bars). Negative values indicate telomere attrition and positive values telomeric gain.
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pone-0002143-g001: The consequences of infection on telomere length.Change of telomere length (mean±s.e.m.) of WBCs from sham-infected controls (white bars) versus infected mice that still harboured Salmonella at termination (grey bars). Negative values indicate telomere attrition and positive values telomeric gain.

Mentions: We examined changes in telomeres in WBCs over nine months and five consecutive infections and found that the experimentally infected males showed significantly greater telomere attrition compared to sham-infected controls (Wilcoxon Signed Ranks test: Z = −2.35, N = 24, P = 0.01; the infected brother showed more attrition compared to sham-infected brother in 10 out of 12 pair-wise sib-sib comparisons). Unlike males, infection did not affect the telomeres of the females (Z = −0.76, N = 20, P = 0.28; the infected sister showed more telomere attrition than sham sister in 7 out of 10 pair-wise comparisons), and this sex-difference in telomere dynamics could be due to males being more susceptible and incurring greater pathology from Salmonella infection than females (see above). When we excluded individuals that were resistant and cleared infection by the end of the experiment from our analyses, we found that infected males still had significantly shorter telomeres than controls (Z = −2.22, N = 22, P = 0.02; Fig. 1; the infected brother showed more attrition compared to sham in 9 out of 11 pair-wise comparisons) and infected females also showed a marginally significant difference from controls (Z = −1.75, N = 10, P = 0.05; Fig. 1; the infected sister showed more attrition than sham in 4 out of 5 pair-wise comparisons). The differences we found between the treatment and control mice were partly due to telomere shortening in infected animals, and, somewhat surprisingly, telomere elongation in sham-controls (which we have observed previously [5]). Taken together, these results provide experimental evidence for the idea that infection causes damage to telomeric DNA, and are consistent with observational findings that lymphocytes develop shorter telomeres due to repeated antigenic stimulation [3], [4], [9]. An alternative possibility we can not rule out is that infection causes a shift in lymphocyte cell subpopulations having shorter telomeres [10]. In this case, telomere length would nevertheless provide a biomarker of exposure to infectious agents.


Telomere attrition due to infection.

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

The consequences of infection on telomere length.Change of telomere length (mean±s.e.m.) of WBCs from sham-infected controls (white bars) versus infected mice that still harboured Salmonella at termination (grey bars). Negative values indicate telomere attrition and positive values telomeric gain.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0002143-g001: The consequences of infection on telomere length.Change of telomere length (mean±s.e.m.) of WBCs from sham-infected controls (white bars) versus infected mice that still harboured Salmonella at termination (grey bars). Negative values indicate telomere attrition and positive values telomeric gain.
Mentions: We examined changes in telomeres in WBCs over nine months and five consecutive infections and found that the experimentally infected males showed significantly greater telomere attrition compared to sham-infected controls (Wilcoxon Signed Ranks test: Z = −2.35, N = 24, P = 0.01; the infected brother showed more attrition compared to sham-infected brother in 10 out of 12 pair-wise sib-sib comparisons). Unlike males, infection did not affect the telomeres of the females (Z = −0.76, N = 20, P = 0.28; the infected sister showed more telomere attrition than sham sister in 7 out of 10 pair-wise comparisons), and this sex-difference in telomere dynamics could be due to males being more susceptible and incurring greater pathology from Salmonella infection than females (see above). When we excluded individuals that were resistant and cleared infection by the end of the experiment from our analyses, we found that infected males still had significantly shorter telomeres than controls (Z = −2.22, N = 22, P = 0.02; Fig. 1; the infected brother showed more attrition compared to sham in 9 out of 11 pair-wise comparisons) and infected females also showed a marginally significant difference from controls (Z = −1.75, N = 10, P = 0.05; Fig. 1; the infected sister showed more attrition than sham in 4 out of 5 pair-wise comparisons). The differences we found between the treatment and control mice were partly due to telomere shortening in infected animals, and, somewhat surprisingly, telomere elongation in sham-controls (which we have observed previously [5]). Taken together, these results provide experimental evidence for the idea that infection causes damage to telomeric DNA, and are consistent with observational findings that lymphocytes develop shorter telomeres due to repeated antigenic stimulation [3], [4], [9]. An alternative possibility we can not rule out is that infection causes a shift in lymphocyte cell subpopulations having shorter telomeres [10]. In this case, telomere length would nevertheless provide a biomarker of exposure to infectious agents.

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