Highlights ? Circulating DHEAS levels are highly elevated in young adults and subsequently show a marked age-related decline. ? In rhesus monkeys, plasma DHEAS has a well-defined diurnal rhythm, with peaks in the morning. ? Despite early promise, recent findings suggest that circulating DHEAS levels may not be good biomarkers of aging in calorie restriction studies. Urbanski HF, Mattison JA, Roth GS, Ingram DK. Dehydroepiandrosterone sulfate (DHEAS) as an endocrine marker of aging in calorie restriction studies. Exp Gerontol. ScienceDirect.com - Experimental Gerontology - Dehydroepiandrosterone sulfate (DHEAS) as an endocrine marker of aging in calorie restriction studies 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.