Light buckets and laser beams: mechanisms and applications of photobiomodulation (PBM) therapy

Abstract

Photobiomodulation (PBM) therapy, a non-thermal light therapy using nonionizing light sources, has shown therapeutic potential across diverse biological processes, including aging and age-associated diseases. In 2023, scientists from the National Institute on Aging (NIA) Intramural and Extramural programs convened a workshop on the topic of PBM to discuss various proposed mechanisms of PBM action, including the stimulation of mitochondrial cytochrome C oxidase, modulation of cell membrane transporters and receptors, and the activation of transforming growth factor-β1. They also reviewed potential therapeutic applications of PBM across a range of conditions, including cardiovascular disease, retinal disease, Parkinson's disease, and cognitive impairment. Workshop participants largely agreed that PBM holds immense potential as a safe and effective therapeutic approach for a wide range of age-related diseases and cognitive decline. While further research is needed to fully elucidate its mechanisms and optimize treatment protocols, the findings presented at the NIA workshop provide strong evidence for the continued investigation and clinical translation of this promising, inexpensive, safe technology, to aging and age-associated diseases. Here, we review the research presented and discussion held at the meeting. In addition, the text has been updated, where applicable, with recent research findings that have been made since the meeting occurred.

Keywords: Aging and age-associated diseases; Mitochondrial cytochrome C oxidase (CcO); Near-infrared (NIR) Light; Neuroprotection; Non-ionizing light therapy; Non-thermal light therapy; Photobiomodulation therapy; Therapeutic applications of light; Transforming growth factor-β1 (TGF-β1).

Fig. 1

Three proposed mechanisms of action for PBM. (Adapted from P. Arany, 2019)

Fig. 2

A Model of the photobiochemical mechanism of action of infrared light on the measured cytochrome c oxidase oxidation (CcO oxidized) and hemoglobin oxygenation (HbO₂) during 1064-nm laser stimulation. B A flow chart illustrating the conventional neuro-vascular coupling by the black-colored notations and PBM-induced metabolic-hemodynamic coupling by the red-colored notations. The blue-colored notations represent common endpoints of both mechanisms on cerebral circulation. Adapted from Wang et al. (2017)

Fig. 3

Biphasic PBM dose curve on levels of TGF-β1. Biphasic PBM dose curve showing activation of latent TGF-β1 in serum. TGF-b1 activation in serum after treatment with a low-power laser at increasing fluences assessed with ELISA. Adapted from Arany (2014)

Fig. 4

Effect of Age and PBM treatment on aortic stiffness assessed as aortic pulse wave velocity (PWV). Aged C57/BL6 mice. PBM-treated mice exposed to NIR light (3 J/cm.², 2 min/d, 5 d/w; 850 nm). Timepoints around each age are offset for visualization purposes. Error bars indicate SD; numbers on the lower part of the figure represent the combined number of untreated and treated male and female mice at each age. Redrawn from data in Ahmet et al. (2023)

Fig. 5

Overall accuracy on the Wisconsin Card Sort Task across all trials for the two groups. a The active PBM laser treatment group correctly sorted the cards more often than the placebo group. b Trials to criterion for each of the first four rules learned. The placebo treatment group took significantly longer to reach criterion on the second rule than the active laser treatment group, suggesting a benefit in set‐shifting ability in the active treatment group. Error bars represent standard errors. Reproduced from Blanco et al. (2017)