This review summarises the current state of knowledge regarding the physiology and control of production of thyroid hormones, the effects of chemicals in perturbing their synthesis and release that result in thyroid cancer. It does not consider the potential neurodevelopmental consequences of low thyroid hormones. There are a number of known molecular initiating events (MIEs) that affect thyroid hormone synthesis in mammals and many chemicals are able to activate multiple MIEs simultaneously. AOP analysis of chemical-induced thyroid cancer in rodents has defined the key events that predispose to the development of rodent cancer and many of these will operate in humans under appropriate conditions, if they were exposed to high enough concentrations of the affecting chemicals. There are conditions however that, at the very least, would indicate significant quantitative differences in the sensitivity of humans to these effects, with rodents being considerably more sensitive to thyroid effects by virtue of differences in the biology, transport and control of thyroid hormones in these species as opposed to humans where turnover is appreciably lower and where serum transport of T4/T3 is different to that operating in rodents. There is heated debate around claimed qualitative differences between the rodent and human thyroid physiology, and significant reservations, both scientific and regulatory, still exist in terms of the potential neurodevelopmental consequences of low thyroid hormone levels at critical windows of time. In contrast, the situation for the chemical induction of thyroid cancer, through effects on thyroid hormone production and release, is less ambiguous with both theoretical, and actual data, showing clear dose-related thresholds for the key events predisposing to chemically induced thyroid cancer in rodents. In addition, qualitative differences in transport, and quantitative differences in half life, catabolism and turnover of thyroid hormones, exist that would not operate under normal situations in humans.

The mouse has rapidly become the mammalian model organism of choice in ageing research due to its relatively short lifespan, the proximity of its genome and physiology to humans, and most importantly due to its genetic pliability and the availability of mutant strains. Mouse models have provided great insights into the ageing process, which in its broadest sense is the progressive decline of body functions over time. In this mini-review, we briefly cover the historical views on the link between ageing and metabolic rate, highlight genetically modified transgenic mouse models of extended lifespan, discuss endocrine pathways linked to senescence and ageing, and then examine pathways by which caloric restriction is postulated to result in longevity.