Cumulative stress in research animals: Telomere attrition as a biomarker in a welfare context?

Abstract

Progress in improving animal welfare is currently limited by the lack of objective methods for assessing lifetime experience. I propose that telomere attrition, a cellular biomarker of biological age, provides a molecular measure of cumulative experience that could be used to assess the welfare impact of husbandry regimes and/or experimental procedures on non-human animals. I review evidence from humans that telomere attrition is accelerated by negative experiences in a cumulative and dose-dependent manner, but that this attrition can be mitigated or even reversed by positive life-style interventions. Evidence from non-human animals suggests that despite some specific differences in telomere biology, stress-induced telomere attrition is a robust phenomenon, occurring in a range of species including mice and chickens. I conclude that telomere attrition apparently integrates positive and negative experience in an accessible common currency that translates readily to novel species--the Holy Grail of a cumulative welfare indicator.

Keywords: animal welfare; biological age; biomarker; cumulative experience; cumulative severity; stress; telomere dynamics.

Figure 1

Summary of the some of the known relationships between organism‐level experiences, the cellular environment and telomere dynamics in humans. In general, it appears that negative experiences shorten telomeres, whereas positive experiences can retard, prevent or possibly reverse telomere attrition. References for the associations shown in this figure are given in Table 1 and Section 3 of the text.

Figure 2

Examples of proposed effects of age and stress on TL between two time points, t ₁ and t ₂. TA for the time period between t ₁ and t ₂ corresponds to the difference in TL between these two time points (indicated by the two‐ended arrows). Part A shows the change in telomere length over time for an animal that is not exposed to any stressful experiences (i.e. the age‐dependent component of my model). Part B shows the change in telomere length over time for the same animal exposed to three stressors (indicated by red bars) each of the same duration but of progressively decreasing amplitude (indicated by the height of the bars). This situation could pertain to an animal that is repeatedly subjected to the same stressful procedure, but that habituates to this procedure such that the amplitude of its stress response decreases with each exposure. Note that the rate of change in TL is greater during the periods of stress and is proportional to the amplitude of the stressors, but returns to the baseline rate of A at the end of each stressor. TA_B is greater than TA_A, reflecting the greater cumulative severity in B.