Adrenopause

The senescent decline of the production of dehydroepiandrosterone and its sulfate (DHEA(S)) by the human adrenal cortex is referred to as adrenopause. As an age-related biological phenomenon, it presents special challenges for appropriate modeling because it is only known to occur in humans. Rodents generally do not synthesize these steroids and primates that have human-like adrenal glands are often not ideal for use in biomedical research. The hypothesis put forward here is that the creation of a humanized mouse model could be very valuable in modeling and understanding adrenopause. Two types of humanized mouse models are proposed: genetically modified mice that faithfully mimic human adrenal steroidogenesis and immunodeficient mice with transplanted human adrenal organoids that synthesize DHEA(S). Significant challenges exist with respect to both forms of humanized mouse models for adrenopause.