摘要： Background and Objectives: In our previous proof‐of‐principle study, transcranial photobiomodulation (tPBM) with 1,064‐nm laser was reported to significantly increase concentration changes of oxygenated hemoglobin (Δ[HbO]) and oxidized‐state cytochrome c oxidase (Δ[oxi‐CCO]) in the human brain. This paper further investigated (i) its validity in two different subsets of young human subjects at two study sites over a period of 3 years and (ii) age‐related effects of tPBM by comparing sham‐controlled increases of Δ[HbO] and Δ[oxi‐CCO] between young and older adults. Study Design/Materials and Methods: We measured sham‐controlled Δ[HbO] and Δ[oxi‐CCO] using broadband near‐infrared spectroscopy (bb‐NIRS) in 15 young (26.7 ± 2.7 years of age) and 5 older (68.2 ± 4.8 years of age) healthy normal subjects before, during, and after right‐forehead tPBM/sham stimulation with 1,064‐nm laser. Student t tests were used to test statistical differences in tPBM‐induced Δ[HbO] and Δ[oxi‐CCO] (i) between the 15 young subjects and those of 11 reported previously and (ii) between the two age groups measured in this study. Results: Statistical analysis showed that no significant difference existed in Δ[HbO] and Δ[oxi‐CCO] during and post tPBM between the two subsets of young subjects at two study sites over a period of 3 years. Furthermore, the two age groups showed statistically identical net increases in sham‐controlled Δ[HbO] and Δ[oxi‐CCO]. Conclusions: This study provided strong evidence to validate/confirm our previous findings that tPBM with 1,064‐nm laser enables to increase cerebral Δ[HbO] and Δ[oxi‐CCO] in the human brain, as measured by bb‐NIRS. Overall, it demonstrated the robust reproducibility of tPBM being able to improve cerebral hemodynamics and metabolism of the human brain in vivo in both young and older adults.