A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 8-Week Pilot Study of Tuna-Byproduct-Derived Novel Supplements for Managing Cellular Senescence and Cognitive Decline in Perimenopausal and Postmenopausal Women.

Due to the lack of clinical data, we aimed to assess the anti-cellular senescence and cognition-enhancing effects and the mechanisms of novel tuna-byproduct-derived supplements. An 8-week, three-arm, randomized, double-blind, placebo-controlled parallel study was performed. A total of 60 female perimenopausal and postmenopausal women (45-60 years old) were randomly assigned to placebo, low (2600 mg/day), and high (6000 mg/day) doses of the supplement. The N100 and P300 brain waves, working memory, serum levels of MDA, SOD, CAT, GPx TNF-α, IL-6, eNOS, AChE, MAO, GABA-T, and SIRT1, and density of Lactobacillus and Bifidobacterium spp. in feces were assessed before consumption and every 4 weeks throughout the study period. The telomere length and total phenolic compound and DHA levels were assessed before and at the end of the study. The low dose increased the N100 amplitude, working memory, telomere length, and SIRT1, whereas high doses improved the amplitudes of N00 and P300, P300 latency, and working memory; suppressed AChE, MAO, and GABA-T; and improved MDA, SOD, GPx, TNF-α, and IL-6 levels in the serum, further exhibiting an increase in DHA. Therefore, the novel supplement could be a potential remedy for managing cellular senescence and cognitive decline in perimenopausal and postmenopausal women; however, studies with larger sample sizes are required.