Milk-based culture of Penicillium camemberti and its component oleamide affect cognitive function in healthy elderly Japanese individuals: a multi-arm randomized, double-blind, placebo-controlled study.

Dairy products and fermented foods have a reported association with maintained cognitive function. Camembert cheese, a dairy product fermented by the white mold Penicillium camemberti, has also been shown to enhance cognitive function in vivo. Oleamide, derived from the fermentation of the white mold, is a candidate for an active component, and expected to improve both cognitive function and sleep conditions. Thus, this study investigated whether the milk-based culture of white mold (MCW), and oleamide, could improve cognitive function and sleep state clinically. A multi-arm randomized, double-blind, placebo-controlled trial was conducted in Tokyo, Japan. 60 healthy Japanese individuals aged 50-75 who were aware of their cognitive decline were randomly and equally divided into three groups of 20 participants using computer-generated random numbers. Participants took either MCW (equivalent to 60 µg/day of oleamide), 60 µg/day of oleamide, or placebo capsules for 12 weeks. Serum BDNF, cognitive function by Cognitrax as primary and MCI Screen as secondary outcome, and sleep status using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) were assessed before and after intervention. The participants, outcome assessors and analysts, and research assistants were blinded to the group assignment. Of the 60 participants, 58 completed the study and were analyzed. No adverse events related to test foods were observed. The placebo group showed a negative rate of change in serum BDNF (-10.5% ± 19.7%), whereas the MCW and oleamide groups showed positive changes (2.0% ± 27.1% and 1.3% ± 13.5%, respectively). Cognitrax scores increased after 12 weeks in all groups. Conversely, the MPI score of the MCI Screen demonstrated a significant improvement in the MCW and oleamide groups compared to the placebo group (p = 0.013 and p < 0.001, respectively). The subscales, immediate free recall and delayed free recall, also significantly increased in them compared to the placebo group. Although PSQI-J revealed no significant differences among groups, the MCW and oleamide groups showed significant improvement after intervention in overall score, subjective sleep quality, and sleep latency. Our results suggest that MCW and its component, oleamide, are safe and contribute to maintaining cognitive functions, particularly short-term and working memory, and improving sleep state. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054792, identifier UMIN-CTR UMIN000048084.

Protocol for detecting threonine deaminase activity in fission yeast cell lysates.

Threonine deaminase catalyzes the first step of isoleucine biosynthesis from threonine. In this protocol, we describe the process of measuring the enzymatic activity of threonine deaminase in the fission yeast cell lysate, which is catalyzed by Tda1. First, we describe the process of preparing cell lysates from fission yeast cell cultures. Subsequently, we explain how to measure the threonine deaminase activity using threonine or serine as a substrate. For complete details on the use and execution of this protocol, please refer to Sasaki et al. (2022).1.

Inverse Association between Cheese Consumption and Lower Cognitive Function in Japanese Community-Dwelling Older Adults Based on a Cross-Sectional Study.

Diet modification may contribute to the prevention of age-related cognitive decline. The association between dairy product consumption and cognitive function in older people remains unknown. We investigated whether cheese intake is associated with lower cognitive function (LCF) in community-dwelling older adults. This cross-sectional study included 1503 adults aged over 65 years. The analyzed data were obtained through face-to-face interviews and functional ability measurement. Cognitive function was assessed using the mini-mental state examination (MMSE), and a score ≤23 was defined as LCF. The prevalence of LCF was 4.6%, and this group had smaller calf circumference, slower usual walking speed, and a more frequent history of anemia than subjects with MMSE scores >23. After adjusting for confounding factors, logistic regression analysis revealed cheese intake (odds ratio (OR) = 0.404, 95% confidence interval (CI) = 0.198-0.824), age (OR = 1.170, 95% CI = 1.089-1.256), usual walking speed (OR = 0.171, 95% CI = 0.062-0.472) and calf circumference (OR = 0.823, 95% CI = 0.747-0.908) to be significant factors associated with LCF. Although the present study was an analysis of cross-sectional data of Japanese community-dwelling older adults, the results suggest that cheese intake is inversely associated with LCF.

FK506-binding protein, FKBP12, promotes serine utilization and negatively regulates threonine deaminase in fission yeast.

FK506-binding protein with a molecular weight of 12 kDa (FKBP12) is a receptor of the immunosuppressive drugs, FK506 and rapamycin. The physiological functions of FKBP12 remain ambiguous because of its nonessentiality and multifunctionality. Here, we show that FKBP12 promotes the utilization of serine as a nitrogen source and regulates the isoleucine biosynthetic pathway in fission yeast. In screening for small molecules that inhibit serine assimilation, we found that the growth of fission yeast cells in medium supplemented with serine as the sole nitrogen source, but not in glutamate-supplemented medium, was suppressed by FKBP12 inhibitors. Knockout of FKBP12 phenocopied the action of these compounds in serine-supplemented medium. Metabolome analyses and genetic screens identified the threonine deaminase, Tda1, to be regulated downstream of FKBP12. Genetic and biochemical analyses unveiled the negative regulation of Tda1 by FKBP12. Our findings reveal new roles of FKBP12 in amino acid biosynthesis and nitrogen metabolism homeostasis.