| Abstract: Bone-derived factors, also known as osteokine, are bioactive factors and peptides mainly secreted by bone tissue cells. Previous studies have shown that bone-derived factors act on pancreas, fat, liver, and other tissues or organs, participate in the regulation of organism energy metabolism, and thus play an important regulatory role in the pathophysiology of metabolic diseases such as diabetes. Recent studies have confirmed that bone-derived factors such as osteocalcin, fibroblast growth factor 23, dickkopf-related protein 1, sclerosin, and lipocalin 2, among others, may enter the brain through blood circulation, and regulate cognitive function via promoting the anabolism of monoamine neurotransmitters and the expression of brain-derived neurotrophic factor, inducing neurogenesis, improving synaptic plasticity, enhancing neuronal autophagy, and maintaining ion metabolism and microenvironment homeostasis. In-depth exploring the potentially biological link between bone-derived factors and brain may help to further screen targeted drugs to delay the decline of cognitive function, and to open up new ideas for formulating intervention programs to promote brain health in the elderly. |