Buckwheat Flour and Its Starch Prevent Age-Related Cognitive Decline by Increasing Hippocampal BDNF Production in Senescence-Accelerated Mouse Prone 8 Mice

Katayama, Shigeru; Okahata, Chizuru; Onozato, Masashi; Minami, Tōru; Maeshima, Masanaga; Ogihara, Kazuaki; Yamazaki, Shinya; Takahashi, Yuta; Nakamura, Soichiro

doi:10.3390/nu14132708

Cited by 8 publications

(8 citation statements)

References 33 publications

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“…In our research, perhexiline, as a KLF14 agonist, enhanced cell proliferation, DNA synthesis, and DNA damage repair to inhibit cellular senescence by promoting the expression of POLD1. We also conducted in vivo experiments to verify the anti-aging function of perhexiline in SAMP8 mice, which exhibited accelerated aging with a shortened life span and age-related deteriorations in multiple tissues 65 . Notably, the treatment of SAMP8 mice with perhexiline improved cognitive function and reduced tissue lesions.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of KLF14 accelerated cellular senescence and aging

Hou¹,

Qiao²,

Wang

et al. 2023

Preprint

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Aging has been considered as a risk factor in many diseases, thus, comprehensively understanding the cellular and molecular mechanisms of delayed aging is important. Here we investigated whether KLF14 is a suppressor of cellular senescence and aging. In our research, KLF14 levels significantly decreased not only in the serum and lymphocytes of healthy people but also in the cells and tissues of mice with aging. We performed in vitro and in vivo experiments on cells and mice to reveal the function of KLF14 in aging. KLF14 deficiency facilitates cellular senescence and aging-related pathologies in C57BL/6 mice, whereas KLF14 overexpression attenuates cellular senescence. Mechanistically, KLF14 delays aging by binding to the POLD1 promoter to positively regulate POLD1 expression. Remarkably, cellular senescence mediated by KLF14 downregulation could be alleviated by POLD1expression. In addition, perhexiline, an agonist of KLF14, could delay cellular senescence and aging-related pathologies in SAMP8 mice by inducing POLD1 expression, as perhexiline could enhance the effect of KLF14’s transcription activation to POLD1 by elevating the binding level of KLF14 to the POLD1 promoter. Our data indicate that KLF14 might be a critical element in aging by upregulating POLD1 expression, indicating that the activation of KLF14 may delay aging and aging-associated diseases.

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Section: Discussionmentioning

confidence: 99%

Downregulation of KLF14 accelerated cellular senescence and aging

Hou¹,

Qiao²,

Wang

et al. 2023

Preprint

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“…In this regard, food, exercise, and an enriched environment are considered as positive modulators [20,[43][44][45], while neuroinflammation, infections, and ageing have been proposed as negative regulators [15,[46][47][48]. Several studies have reported a characteristic age-associated decrease in Gdnf gene expression patterns in different rodent strains [49][50][51]. Consistent with these findings, the current results showed that ageing significantly affected the expression of both Gdnf and GFRα1 genes in CD-1 mice, with lower expression detected in 15-months-old relative to 3-months-old mice.…”

Section: Accelerated Age-associated Decline In Hippocampal Gdnf/gfrα1...mentioning

confidence: 99%

“…The neurological bases of AACD have been extensively explored, with current evidence highlighting the influence of alterations in synapsis-related proteins, neurotrophic factors, and histone modifications [6,36,50]. However, most studies conducted in this regard have not addressed the potential interference of gestational inflammation on manifestations of AACD in the direct or second-generation progeny.…”

Section: Potential Interplay Between Gestational Inflammation and Red...mentioning

confidence: 99%

Effects of gestational inflammation on age-related cognitive decline and hippocampal Gdnf-GFRα1 levels in F1 and F2 generations of CD-1 Mice

et al. 2023

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Background It has been reported that age-associated cognitive decline (AACD) accelerated by maternal lipopolysaccharide (LPS) insult during late pregnancy can be transmitted to the second generation in a sex-specificity manner. In turn, recent studies indicated that glial cell line‐derived neurotrophic factor (GDNF) and its cognate receptor (GFRα1) are critical for normal cognitive function. Based on this evidence, we aimed to explore whether Gdnf-GFRα1 expression contributes to cognitive decline in the F1 and F2 generations of mouse dams exposed to lipopolysaccharide (LPS) during late gestation, and to evaluate also the potential interference effect of pro-inflammatory cytokines. Methods During gestational days 15–17, pregnant CD-1 mice (8–10 weeks old) received a daily intraperitoneal injection of LPS (50 μg/kg) or saline (control). In utero LPS-exposed F1 generation mice were selectively mated to produce F2 generation mice. In F1 and F2 mice aged 3 and 15 months, the Morris water maze (MWM) was used to evaluated the spatial learning and memory ability, the western blotting and RT-PCR were used for analyses of hippocampal Gdnf and GFRα1 expression, and ELISA was used to analyse IL-1β, IL-6 and TNF-α levels in serum. Results Middle-aged F1 offspring from LPS-treated mothers exhibited longer swimming latency and distance during the learning phase, lower percentage swimming time and distance in targe quadrant during memory phase, and lower hippocampal levels of Gdnf and GFRα1 gene products compared to age-matched controls. Similarly, the middle-aged F2 offspring from the Parents-LPS group had longer swimming latency and distance in the learning phase, and lower percentage swimming time and distance in memory phase than the F2-CON group. Moreover, the 3-month-old Parents-LPS and 15-month-old Parents- and Father-LPS groups had lower GDNF and GFRα1 protein and mRNAs levels compared to the age-matched F2-CON group. Furthermore, hippocampal levels of Gdnf and GFRα1 were correlated with impaired cognitive performance in the Morris water maze after controlling for circulating pro-inflammatory cytokine levels. Conclusions Our findings indicate that accelerated AACD by maternal LPS exposure can be transmitted across at least two generations through declined Gdnf and GFRα1 expression, mainly via paternal linage.

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“…17,18 Many studies have reported that BDNF expression and the activation of its transcription factor, cAMP response element-binding protein (CREB), decrease significantly in SAMP8 aging mice, compared with SAMR1 mice. [19][20][21][22] However, dietary intake of phytochemicals 19,20 and plant food components 21,22 can attenuate age-related cognitive impairment by the activation of the CREB/BDNF pathway in SAMP8 mice. Overall, the induction of BDNF seems to contribute to the prevention of age-related cognition decline and memory loss.…”

Section: Introductionmentioning

confidence: 99%