unclear due to the inabilities to access live samples. Recent progress in organiod, such as a 3D brain structure developed from human pluripotent cells [44], provides promising methods to test drugs in a human brain microenvironment [45]. By contrast, exercise is more easily applicable in humans and along with the recent advances in non-invasive imaging technology like MRI and PET that measure neurogenesis in human [2], transferring exercise-related researches into human trails would be possible. Furthermore, as interaction between BDNF and IGF-1 has been identified in the mechanism of exercise-induced cognitive amelioration, it is reasonable to speculate that interaction effects of these two factors also exist in other mechanisms affecting neurogenesis. Further studies are needed to explore the comprehensive relationship between BDNF and IGF-1. In conclusion, advances in technology development allow further studies to understand the age-associated neurogenesis in human hippocampus and confirm potential strategies to restore the decline. And, BDNF and IGF-1 are important targets to discover novel alternatives that intervene brain-ageing process.