AbstractBackgroundPhotobiomodulation (PBM) therapy, a form of low‐dose light therapy, has been noted to be effective in several age‐associated chronic diseases such as hypertension and atherosclerosis. Here, we examined the effects of PBM therapy on age‐associated cardiovascular changes in a mouse model of accelerated cardiac aging.MethodsFourteen months old Adenylyl cyclase type VIII (AC8) overexpressing transgenic mice (n = 8) and their wild‐type (WT) littermates (n = 8) were treated with daily exposure to Near‐Infrared Light (850 nm) at 25 mW/cm2 for 2 min each weekday for a total dose of 1 Einstein (4.5 p.J/cm2 or fluence 3 J/cm2) and compared to untreated controls over an 8‐month period. PBM therapy was administered for 3.5 months (Early Treatment period), paused, due to Covid‐19 restrictions for the following 3 months, and restarted again for 1.5 months. Serial echocardiography and gait analyses were performed at monthly intervals, and serum TGF‐β1 levels were assessed following sacrifice.ResultsDuring the Early Treatment period PBM treatments: reduced the age‐associated increases in left ventricular (LV) mass in both genotypes (p = 0.0003), reduced the LV end‐diastolic volume (EDV) in AC8 (p = 0.04); and reduced the left atrial dimension in both genotypes (p = 0.02). PBM treatments substantially increased the LV ejection fraction (p = 0.03), reduced the aortic wall stiffness (p = 0.001), and improved gait symmetry, an index of neuro‐muscular coordination (p = 0.005). The effects of PBM treatments, measured following the pause, persisted. Total TGF‐β1 levels were significantly increased in circulation (serum) in AC8 following PBM treatments (p = 0.01). We observed a striking increase in cumulative survival in PBM‐treated AC8 mice (100%; p = 0.01) compared to untreated AC8 mice (43%).ConclusionPBM treatment mitigated age‐associated cardiovascular remodeling and reduced cardiac function, improved neuromuscular coordination, and increased longevity in an experimental animal model. These responses correlate with increased TGF‐β1 in circulation. Future mechanistic and dose optimization studies are necessary to assess these anti‐aging effects of PBM, and validation in future controlled human studies is required for effective clinical translation.