Aging, glucocorticoids and developmental programming

Abstract

Glucocorticoids are pleiotropic regulators of multiple cell types with critical roles in physiological systems that change across the life-course. Although glucocorticoids have been associated with aging, available data on the aging trajectory in basal circulating glucocorticoids are conflicting. A literature search reveals sparse life-course data. We evaluated (1) the profile of basal circulating corticosterone across the life-course from weaning (postnatal day-PND 21), young adult PND 110, adult PND 450, mature adult PND 650 to aged phase PND 850 in a well-characterized homogeneous rat colony to determine existence of significant changes in trajectory in the second half of life; (2) sex differences; and (3) whether developmental programming of offspring by exposure to maternal obesity during development alters the later-life circulating corticosterone trajectory. We identified (1) a fall in corticosterone between PND 450 and 650 in both males and females (p < 0.05) and (2) higher female than male concentrations (p < 0.05). (3) Using our five life-course time-point data set, corticosterone fell at a similar age but from higher levels in male and female offspring of obese mothers. In all four groups studied, there was a second half of life fall in corticosterone. Higher corticosterone levels in offspring of obese mothers may play a role in their shorter life-span, but the age-associated fall occurs at a similar time to control offspring. Although even more life-course time-points would be useful, a five life-course time-point analysis provides important new information on normative and programmed aging of circulating corticosterone.

Fig. 1

Proposed strategy to determine at five life-course time-points. The timing of an age-related change represented by dash line in a variable that increases (a–d) or decreases (e–h) with age. a, e Represent a normal; b, f a premature; c, g an augmented; and d, h a premature and augmented aging process

Fig. 2

Plasma corticosterone in a male and b female control rats (open histograms) at five life-course stages (PND postnatal day). The yen sign indicates the first significant change when comparing each age with the one prior starting with the oldest age as described for the analysis used in Fig. 1. Data are also presented (solid histogram) for F₁ of obese mothers a male and b female. Data are mean ± SEM; group n = 5–14. Data were in-transformed, and sexes were analyzed separately. Female corticosterone values were higher than male in all groups at all ages except in offspring of obese group at PND 110 (downward-pointing arrow). For the timing of the corticosterone fall in each group analysis was as described in relation to Fig. 1. For C vs. obese at the three ages in each sex, two-way ANOVA with Sidak’s multiple comparison tests. p < 0.05 (asterisk) vs. C