Periodic Reporting for period 1 - NARESICA (Mechanisms linking stress and ageing in two avian species exhibiting contrasted natural resistance to stress (NAtural REsistance to Stress-Induced Cellular Ageing))
Période du rapport: 2021-09-01 au 2023-08-31
NARESICA employed experimental approaches manipulating stress exposure and glucocorticoid hormones in captive Japanese quail and wild king penguins and measured the resulting impact on growth rate, telomere shortening and its potential cellular drivers (mitochondrial function, oxidative stress, mTOR cellular signaling).
In wild king penguins, we used subcutaneous implants of glucocorticoid hormone (or placebo) in chicks and measured the impact on their growth, behavior, physiology and survival over ca. 150 days. While our experimental manipulation was successful in raising circulating glucocorticoid levels, we did not detect any significant deleterious impact on growth, survival or physiology, including telomere length, a biomarker of ageing. Specifically, chicks implanted with glucocorticoid grew slightly faster than placebo ones, experienced less oxidative damage to DNA and had preserved telomere length, partly owing to the up-regulation of genes involved in telomere maintenance. These results have been presented at the CEPA meeting in Montpellier (2021) and at the Society for Experimental Biology annual meeting (2022). The manuscript is close to submission, waiting for available funding to re-analyze part of the samples for telomere length using an alternative technique following reviewer’s comments.
In captive Japanese quails, the initial plans of NARESICA have been up-graded thanks to the collaboration of INRAE (Tours), which provided individuals coming from artificial selection lines that have been selected for low or high sensitivity to stress based on behavioral response. Individuals from both lines were splitted in three experimental groups: 1. Control, 2. Treated with glucocorticoid hormone through drinking water, 3. Submitted to a chronic stress protocol involving 5 stressor types rotated every weekday. We measured body mass growth, behavior and multiple physiological indicators during the 50 days of treatment. Lines differed markedly in their response to the experimental treatments, with the sensitive line exhibiting a clear drop in body mass growth in response to glucocorticoid supplementation, and a milder reduction in response to chronic stress. In-vitro work on freshly isolated mitochondria from heart demonstrated that the sensitive line showed an improved mitochondrial efficiency in response to chronic stress and glucocorticoid treatments, while this was not the case for the less sensitive line. This could theoretically lead to increased ROS production, oxidative stress and telomere shortening. Laboratory measurements of telomere length, gene expression, oxidative stress and circulating glucocorticoids are ongoing as part of a MSc internship. The preliminary results have been presented at the University of Glasgow in January 2023, for an invited talk in the group of Profs Pat Monaghan and Neil Metcalfe. One manuscript on the effects of the line*treatment interaction on body mass and mitochondrial bioenergetics is in preparation, and another one will be once laboratory results will be obtained for telomeres, gene expression and oxidative stress.