Ano Yasuhisa, Ohya Rena, Takashima Akihiko, Uchida Kazuyuki, Nakayama Hiroyuki
Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Kirin Central Research Institute, Kirin Holdings Company Ltd., Kanagawa, Japan.
Front Nutr. 2021 Aug 23;8:724134. doi: 10.3389/fnut.2021.724134. eCollection 2021.
With the rapid increase in aging populations worldwide, there has been an increase in demand for preventive and therapeutic measures for age-related cognitive decline and dementia. Epidemiological studies show that consumption of dairy products reduces the risk for cognitive decline and dementia in the elderly. We have previously demonstrated in randomized trials that the consumption of β-lactolin, a whey-derived Gly-Thr-Trp-Tyr lactotetrapeptide, improves cognitive function in older adults. Orally administered β-lactolin is delivered to the brain and inhibits monoamine oxidase, resulting in alleviation of memory impairment. However, there is currently no evidence of the effects of long-term β-lactolin intake on aging. Here, we found that the discrimination index in the novel object recognition test for object recognition memory was reduced in mice aged 20 months compared with that in young mice, indicating that age-related cognitive decline was induced in the aged mice; in aged mice fed β-lactolin for 3 months, memory impairment was subsequently alleviated. In aged mice, impairment of light/dark activity cycles was found to be induced, which was subsequently alleviated by β-lactolin consumption. Additionally, the number of activated microglia in the hippocampus and cortex and the production of cytokines (tumor necrosis factor-α, macrophage inflammatory protein-1α, and macrophage chemoattractant protein-1) were increased in aged mice compared with those in young mice but were reduced in aged mice fed β-lactolin. The age-related hippocampal atrophy was improved in aged mice fed β-lactolin. Cytochrome c levels in the hippocampus and cortex were increased in aged mice compared with those in young mice but were also reduced by β-lactolin consumption. These results suggest that β-lactolin consumption prevents neural inflammation and alleviates aging-related cognitive decline.
随着全球老龄化人口的迅速增加，对与年龄相关的认知衰退和痴呆症的预防和治疗措施的需求也在增加。流行病学研究表明，食用乳制品可降低老年人认知衰退和患痴呆症的风险。我们之前在随机试验中证明，食用β-乳球蛋白（一种源自乳清的甘氨酰-苏氨酰-色氨酰-酪氨酰四肽）可改善老年人的认知功能。口服β-乳球蛋白可进入大脑并抑制单胺氧化酶，从而减轻记忆障碍。然而，目前尚无长期摄入β-乳球蛋白对衰老影响的证据。在此，我们发现，与年轻小鼠相比，20个月龄小鼠在新物体识别测试中用于物体识别记忆的辨别指数降低，这表明老年小鼠出现了与年龄相关的认知衰退；在喂食β-乳球蛋白3个月的老年小鼠中，记忆障碍随后得到缓解。在老年小鼠中，发现其明暗活动周期出现障碍，而食用β-乳球蛋白后这种障碍随后得到缓解。此外，与年轻小鼠相比，老年小鼠海马体和皮质中活化小胶质细胞的数量以及细胞因子（肿瘤坏死因子-α、巨噬细胞炎性蛋白-1α和巨噬细胞趋化蛋白-1）的产生增加，但在喂食β-乳球蛋白的老年小鼠中减少。喂食β-乳球蛋白的老年小鼠与年龄相关的海马体萎缩得到改善。与年轻小鼠相比，老年小鼠海马体和皮质中的细胞色素c水平升高，但食用β-乳球蛋白后也降低。这些结果表明，食用β-乳球蛋白可预防神经炎症并减轻与衰老相关的认知衰退。
