Telomere attrition due to infection.

Petteri Ilmonen,Dustin J Penn,Alexander Kotrschal

doi:10.1371/journal.pone.0002143

Abstract

BackgroundTelomeres–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 FindingsWe 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/SignificanceOur 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.

Highlights

Biological aging or senescence may be due to accumulating DNA damage in somatic cells [1,2], including erosion of telomeres, which may be caused by exposure to infectious and inflammatory diseases [3,4] and other forms of oxidative stress [5,6]
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
Telomeres can be repaired by a special reverse transcriptase, but in vitro studies show that telomeres are vulnerable to oxidative damage by reactive oxygen species (ROS) and that oxidative stress impairs the function of telomerase and other mechanisms that repair telomeres [12]

Summary

Introduction

Biological aging or senescence may be due to accumulating DNA damage in somatic cells [1,2], including erosion of telomeres, which may be caused by exposure to infectious and inflammatory diseases [3,4] and other forms of oxidative stress [5,6]. The aim of our study was to test whether repeated exposure to an infectious agent, known to cause inflammation and oxidative stress, results in telomere attrition, and whether more rapid telomere attrition increases mortality. 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. Experiments are needed to determine whether telomere erosion reduces longevity

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Methods

Results