Investigators Throw Genetic Light on Role of DHEAS in Aging and Related Diseases

Researchers have identified eight common genetic variants associated with serum levels of the steroid hormone dehydroepiandrosterone sulphate (DHEAS). Several of the SNPs appear to be associated with changes in gene-expression levels, and the related genes are connected to biological pathways linking DHEAS with aging and age-related diseases including type 2 diabetes and lymphoma.

The international team, led by researchers at King’s College, claim their work is the first to provide direct genetic evidence linking the hormone with the aging process. Their results are published in PLoS Genetics in a paper titled “Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Aging Mechanisms.”

DHEAS is mainly secreted by the adrenal gland and is the most abundant circulating steroid in humans. Levels of the hormone start to decline after the age of 25 and drop by about 95% by the age of 85 years, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or longevity, according to lead author Guangju Zhai, Ph.D., and colleagues.

The exact role of the hormone has to date remained elusive, and no specific genes regulating serum DHEAS concentration have yet been identified. “The physiological function of DHEAS and its importance in maintaining health are poorly understood,” they admit.

To try and determine genetic factors impacting DHEAS levels and perhaps throw light on its physiological role, the researchers carried out a meta-analysis of genome-wide association studies involving a total of 14,846 individuals of European origin. The results identified eight common SNPs  that implicated the potential involvement of the genes BCL2L11, ARPC1A, ZKSCAN5, TRIM4, HHEX, CYP2C9, BMF, and SULT2A1. “These genes have various associations with steroid hormone metabolism and co-morbidities of aging including type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins,” the researchers write.

“This is the first large-scale study to unlock the mystery that has always surrounded DHEAS,” Dr. Zhai claims. “The findings provide us with the basis for future studies to look into potential mechanisms of exactly how DHEAS is involved in ageing. The next important question to try and answer is whether sustained high levels of DHEAS can in fact delay the aging process and prevent age-related diseases.”