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.

Maternal obesity accelerates rat offspring metabolic ageing in a sex‐dependent manner

“…The fall in corticosterone between 450 and 650 days confirms our finding reported previously (Zambrano et al . ). In male MOF 1 by PND 110 the DHEA:corticosterone ratio was already at its lowest level observed, so we cannot determine the timing of any life course associated fall in the ratio without data prior to 110 days.…”

“…We have found that it is preferable to evaluate subjects at at least four ages, spread over as much of the life course as possible, that occur with normative ageing in control offspring (CF 1 ) of normally fed mothers (Zambrano et al . ). The more time points evaluated the stronger the conclusions.…”

“…Thus, to provide the data needed to detect the direction of ageing changes in the fall in rat serum glucocorticoids across the life course resulting from programming, we obtained data at four time points to compare offspring of obese mothers (Zambrano et al . ). In the present study we evaluated programming‐ageing interactions in key metabolic, endocrine and oxidative stress markers at four time points – postnatal day (PND) 36 (puberty), 110 (young adult), 450 (mature adult) and 650 (old adult) – in a colony of rats in which CF 1 start to die spontaneously soon after PND 850.…”

“…; Zambrano et al . ), which represents approximately 50% of the life course of CF 1 . Thus, the period studied represents 75% of the normal life course.…”

Use of Mometasone furoate in prolonged treatment of experimental spinal cord injury in mice: A comparative study of three different glucocorticoids

“…By binding to glucocorticoid receptor (GR), almost ubiquitously expressed, GCs become pleiotropic regulators of multiple cell types, with a wide range of roles in both healthy and diseased individuals [10], assuming a critical role in physiological systems [11].…”