Dehydroepiandrosterone sulfate (DHEAS) as an endocrine marker of aging in calorie restriction studies

Abstract

The adrenal steroid, dehydroepiandrosterone sulfate (DHEAS), is generally regarded as being a reliable endocrine marker of aging, because in humans and nonhuman primates its circulating concentrations are very high during young adulthood, and the concentrations then decline markedly during aging. Despite promising results from early studies, we were recently surprised to find that caloric restriction (CR) did little to prevent or delay the decline of DHEAS concentrations in old rhesus macaques. Here we summarize the use of circulating DHEAS concentrations as a biomarker of aging in CR studies and suggest reasons for its limited value. Although DHEAS can reliably predict aging in animals maintained on a standard diet, dietary manipulations may affect liver enzymes involved in the metabolism of steroid hormones. Consequently, in CR studies the reliability of using DHEAS as a biomarker of aging may be compromised.

Keywords: Adrenal gland; Biomarker; Cortisol; DHEAS; Rhesus macaque.

Fig. 1

Effect of age and dietary manipulation on the circulating 24-h patterns of DHEAS in male rhesus macaques maintained at the ONPRC. Left panel: mean plasma DHEAS profiles from young (~11 years old, n = 5) and old (~27 years old, n = 6) controls are represented by black and white symbols, respectively. Right panel: mean plasma DHEAS profiles from age-matched young (n = 5) and old (n = 4) monkeys subjected to short-term calorie-restriction (4–5 years; CR) represented by black and white symbols, respectively. The serial blood samples (1 ml) were collected remotely each hour via a subclavian vein catheter, as described (Urbanski 2011). The horizontal black and white bars on the abscissas correspond to the 12L:12D lighting schedule. Two-way analysis of variance (ANOVA) followed by the Newman–Keuls test was used to evaluate group differences (using age and diet as variables). In both the controls and CR monkeys there is a significant (P<0.01) age-related decrease in overall mean DHEAS levels. Importantly, DHEAS levels in the old CR monkeys were not higher than in the age-matched controls. Data adapted from Downs et al., 2008.

Fig. 2

Effect of long-term calorie restriction (14–15 years; CR) on mean (± SEM) serum concentrations of DHEAS and cortisol in middle-aged (17–19 years) and old (~32 years) male rhesus macaques, maintained by the NIA at the NIH Animal Center. Single blood samples (3 ml) were collected by venipuncture 3–4 hours after lights on (i.e., at the time of expected peak) from sedated control and age-matched CR monkeys (gray and black bars, respectively); n = 6–10 animals per group. The main difference between the 17-year-old and the 19-year-old groups is that in the former the caloric restriction was initiated while the monkeys were still prepubertal. Statistical analysis (2-way ANOVA) detected a significant (P<0.05) effect of aging on serum DHEAS concentrations but no effect of diet. There was no obvious effect of age or diet on mean serum cortisol concentrations. These data suggest that CR has no long-term effect on maintaining elevated serum DHEAS concentrations; the DHEAS levels were already highly attenuated by middle age (i.e., considerably lower than the DHEAS levels of the young monkeys depicted in Fig. 1), and declined further during old age.