Mechanism and regulation of iron absorption throughout the life cycle

•The fetus absorbs maternal iron through the placenta and is regulated by maternal iron status.•Intestinal iron absorption and its regulatory mechanism in infants are different from that in adults.•Iron homeostasis changes in the elderly. Iron plays a crucial role through various life stages of human. Iron homeostasis is primarily regulated by iron absorption which is mediated via divalent metal-ion transporter 1 (DMT1), and iron export protein ferroportin (FPN), as there is no active pathway for iron excretion from the body. Recent studies have shown that the magnitude of iron absorption changes through various life stages to meet changing iron requirements. This review aims to provide an overview of recent researches on the regulation of iron absorption throughout mammalian life cycle, with the potential to reveal novel molecules and pathways at special stage of life. Such insights may pave the way for new treatments for disorders associated with aberrant iron homeostasis in the future. This review first summarize the mechanism and regulation of iron absorption throughout various life stages, highlighting that regulatory mechanisms have developed to precisely align iron absorption to iron requirements. In adults, iron absorption is enhanced when body is deficient of iron, conversely, iron absorption is reduced when iron demand decreases via systemic regulator Hepcidin and cellular regulation. In the elderly, age-related inflammation, hormonal changes, and chronic diseases may affect the production of Hepcidin, affecting iron absorption. In infants, intestinal iron absorption and its regulatory mechanism are different from that in adults and there might be an alternative pathway independent of DMT1 and FPN due to high iron absorption. Unique to the fetus, iron is absorbed from maternal stores for its own use through the placenta and is regulated by maternal iron status. This review also proposes directions for further studies, offering promising avenues for developing new treatments for disorders associated with aberrant iron homeostasis.