Insulin‐like growth factor‐1 receptor immunoreactive cells are selectively maintained in the paraventricular hypothalamus of calorically restricted mice

Abstract

The mammalian lifespan is dramatically extended by both caloric restriction (CR) and insulin-like growth factor-1 (IGF-1) suppression. Both interventions involve neuroendocrine alterations directed by the hypothalamus. Yet, it remains unclear whether CR exerts its affects by altering central IGF-1 sensitivity. With this question in mind, we investigated the influence of CR and normal aging on hypothalamic IGF-1 sensitivity, by measuring the changes in IGF-1 receptor (IGF-1R) populations. Taking IGF-1 receptor (IGF-1R) immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the paraventricular nucleus (PVN) of Young-ad libitum fed (Young-Al, 6 weeks old), Old-ad libitum fed (Old-Al, 22 months old), and old calorically restricted (Old-CR, 22 months old) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each cross-section of PVN hypothalamus. Ad libitum fed mice show a 37% reduction in IGF-1R immunoreactive cells and a 12% reduction in the total cell population of the PVN with aging. In comparison, caloric-restricted mice show a 33% reduction in IGF-1R immunoreactive cells and a notable 24% decrease in the total cell population with aging. This selective maintenance of IGF-1R expressing cells coupled with the simultaneous loss of non-immunoreactive cells, results in a higher percentage of IGF-1R immunoreactive cells in the PVNs of CR mice. Thus, the decline in the percentage of IGF-1 sensitive cells in the PVN with age is attenuated by CR.