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.
Original language | English (US) |
---|---|
Pages (from-to) | 23-28 |
Number of pages | 6 |
Journal | International Journal of Developmental Neuroscience |
Volume | 25 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2007 |
Externally published | Yes |
Keywords
- Caloric restriction
- Hypothalamus
- IGF-1
- IGF-1 receptor
- IGF-1R
- Paraventricular nucleus
- Six-week-old young mice
- Twenty-two-month-old mice
ASJC Scopus subject areas
- Developmental Neuroscience
- Developmental Biology