1275-nm Photobiomodulation Alleviates Brain Drainage Impairment as a Promising Therapeutic Strategy for Aging-Related Neurological Decline.

Aging imposes a significant socioeconomic and healthcare burden worldwide, while effective therapy is still lacking. Impaired brain drainage and excessive accumulation of metabolites and toxins such as advanced glycation end products (AGEs) are characteristics of aging that contribute to the development of neurological disorders. Recent discoveries have highlighted the role of meningeal lymphatic vessels (MLVs) in the clearance of toxic metabolites, cells, tumors, and viruses from the brain, positioning them as significant targets for the treatment of various brain diseases. In this study, we demonstrate that noninvasive 1275-nm photobiomodulation (PBM) effectively improves brain drainage and promotes lymphatic clearance of AGEs in a D-galactose-induced aging model (AM) in male mice, while being safe due to its minimal thermal effects. These improvements are associated with nitric oxide release-mediated dilation of MLVs. PBM can also effectively ameliorate redox imbalance, neuroinflammation, and neuronal damage, as well as improve spatial learning ability and short-term recognition memory in AM mice. These findings introduce a promising and easily accessible strategy for nonpharmacological phototherapy of meningeal brain drainage and neurological decline in individuals with aging and aging-related neurodegenerative diseases, offering high potential for rapid implementation into routine clinical practice.