東北大学研究者紹介 - 佐藤　亜希子

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サトウ　アキコ

佐藤　亜希子

Akiko Satoh

所属

加齢医学研究所　脳科学研究部門　統合生理学研究分野

職名

准教授

学位

博士（薬学）（富山医科薬科大学）
修士（薬学）（富山医科薬科大学）

researchmap

https://researchmap.jp/asatoh

J-GLOBAL ID

201801001094036148

e-Rad 研究者番号

80800979

研究キーワード 8

栄養・睡眠負荷
カロリー制限
エピゲノム
転写因子
睡眠
視床下部
個体寿命
老化

研究分野 3

ライフサイエンス / 分子生物学 /
ライフサイエンス / 神経科学一般 /
ライフサイエンス / 進化生物学 / 老化生物学

論文 18

Adipocyte-specific inactivation of NAMPT, a key NAD+ biosynthetic enzyme, causes a metabolically-unhealthy lean phenotype in female mice during aging. 国際誌

Nathan Qi, Michael P Franczyk, Shintaro Yamaguchi, Daiki Kojima, Kaori Hayashi, Akiko Satoh, Noboru Ogiso, Takeshi Kanda, Yo Sasaki, Brian N Finck, Brian J DeBosch, Jun Yoshino

American journal of physiology. Endocrinology and metabolism　2024年5月29日

DOI： 10.1152/ajpendo.00313.2023 　

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Nicotinamide adenine dinucleotide (NAD+) is a universal coenzyme regulating cellular energy metabolism in many cell types. Recent studies have demonstrated the close relationships between defective NAD+ metabolism and aging and age-associated metabolic diseases. The major purpose of the present study was to test the hypothesis that NAD+ biosynthesis, mediated by a rate-limiting NAD+ biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT), is essential for maintaining normal adipose tissue function and whole-body metabolic health during the aging process. To this end, we provided in-depth and comprehensive metabolic assessments for female adipocyte-specific Nampt knockout (ANKO) mice during aging. We first evaluated body fat mass in young (≤ 4-month-old), middle aged (10 to 14-month-old), and old (≥ 18-month-old) mice. Intriguingly, adipocyte-specific Nampt deletion protected against age-induced obesity without changing energy balance. However, data obtained from the hyperinsulinemic euglycemic clamp procedure demonstrated that, despite the lean phenotype, old ANKO mice had severe insulin resistance in skeletal muscle, heart, and white adipose tissue (WAT). Old ANKO mice also exhibited hyperinsulinemia and hypoadiponectinemia. Mechanistically, loss of Nampt caused marked decreases in WAT gene expression of lipogenic targets of peroxisome proliferator-activated receptor gamma (PPARγ) in an age-dependent manner. In addition, administration of a PPARγ agonist rosiglitazone restored fat mass and improved metabolic abnormalities in old ANKO mice. In conclusion, these findings highlight the importance of the NAMPT-NAD+-PPARγ axis in maintaining functional integrity and quantity of adipose tissue, and whole-body metabolic function in female mice during aging.
Evaluation of cellular activity in response to sleep deprivation by a comprehensive analysis of the whole mouse brain 査読有り

Takuya Urushihata, Mio Goto, Keiko Kabetani, Mai Kiyozuka, Shiho Maruyama, Shogo Tsuji, Hirobumi Tada, Akiko Satoh

Frontiers in Neuroscience　17　2023年10月19日
出版者・発行元： Frontiers Media SA
DOI： 10.3389/fnins.2023.1252689 　

eISSN：1662-453X

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Sleep deprivation (SD) causes several adverse functional outcomes, and understanding the associated processes can improve quality of life. Although the effects of SD on neuronal activity in several brain regions have been identified, a comprehensive evaluation of the whole brain is still lacking. Hence, we performed SD using two different methods, gentle handling and a dedicated chamber, in targeted recombination in active populations 2 (TRAP2) mice crossed with Rosa-ZsGreen reporter mice and visualized cellular activity in the whole brain. Using the semi-automated post-imaging analysis tool Slice Histology Alignment, Registration, and Cell Quantification (SHARCQ), the number of activated cells was quantified. From the analysis of 14 brain regions, cellular activity was significantly increased in the olfactory areas and decreased in the medulla by the two SD methods. From the analysis of the further subdivided 348 regions, cellular activity was significantly increased in the vascular organ of the lamina terminalis, lateral hypothalamic area, parabigeminal nucleus, ventral tegmental area, and magnocellular reticular nucleus, and decreased in the anterior part of the basolateral amygdalar nucleus, nucleus accumbens, septohippocampal nucleus, reticular nucleus of the thalamus, preoptic part of the periventricular hypothalamic nucleus, ventromedial preoptic nucleus, rostral linear nucleus raphe, facial motor nucleus, vestibular nuclei, and some fiber tracts (oculomotor nerve, genu of corpus callosum, and rubrospinal tract) by the two SD methods. Two subdivided regions of the striatum (caudoputamen and other striatum), epithalamus, vascular organ of the lamina terminalis, anteroventral preoptic nucleus, superior colliculus optic layer, medial terminal nucleus of the accessory optic tract, pontine gray, and fiber tracts (medial lemniscus, columns of the fornix, brachium of the inferior colliculus, and mammillary peduncle) were differentially affected by the two SD methods. Most brain regions detected from these analyses have been reported to be involved in regulating sleep/wake regulatory circuits. Moreover, the results from the connectivity analysis indicated that the connectivity of cellular activity among brain regions was altered by SD. Together, such a comprehensive analysis of the whole brain is useful for understanding the mechanisms by which SD and/or sleep disruption affects brain function.
Sleep-wake patterns are altered with age, Prdm13 signaling in the DMH, and diet restriction in mice. 国際誌査読有り

Shogo Tsuji, Cynthia S Brace, Ruiqing Yao, Yoshitaka Tanie, Hirobumi Tada, Nicholas Rensing, Seiya Mizuno, Julio Almunia, Yingyi Kong, Kazuhiro Nakamura, Takahisa Furukawa, Noboru Ogiso, Shinya Toyokuni, Satoru Takahashi, Michael Wong, Shin-Ichiro Imai, Akiko Satoh

Life science alliance　6　(6)　2023年6月

DOI： 10.26508/lsa.202301992 　

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Old animals display significant alterations in sleep-wake patterns such as increases in sleep fragmentation and sleep propensity. Here, we demonstrated that PR-domain containing protein 13 (Prdm13)+ neurons in the dorsomedial hypothalamus (DMH) are activated during sleep deprivation (SD) in young mice but not in old mice. Chemogenetic inhibition of Prdm13+ neurons in the DMH in young mice promotes increase in sleep attempts during SD, suggesting its involvement in sleep control. Furthermore, DMH-specific Prdm13-knockout (DMH-Prdm13-KO) mice recapitulated age-associated sleep alterations such as sleep fragmentation and increased sleep attempts during SD. These phenotypes were further exacerbated during aging, with increased adiposity and decreased physical activity, resulting in shortened lifespan. Dietary restriction (DR), a well-known anti-aging intervention in diverse organisms, ameliorated age-associated sleep fragmentation and increased sleep attempts during SD, whereas these effects of DR were abrogated in DMH-Prdm13-KO mice. Moreover, overexpression of Prdm13 in the DMH ameliorated increased sleep attempts during SD in old mice. Therefore, maintaining Prdm13 signaling in the DMH might play an important role to control sleep-wake patterns during aging.
SIRT7 Deficiency Protects against Aging-Associated Glucose Intolerance and Extends Lifespan in Male Mice 査読有り

Tomoya Mizumoto, Tatsuya Yoshizawa, Yoshifumi Sato, Takaaki Ito, Tomonori Tsuyama, Akiko Satoh, Satoshi Araki, Kenichi Tsujita, Masaru Tamura, Yuichi Oike, Kazuya Yamagata

Cells　11　(22)　3609-3609　2022年11月15日
出版者・発行元： MDPI AG
DOI： 10.3390/cells11223609 　

eISSN：2073-4409

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Sirtuins (SIRT1–7 in mammals) are evolutionarily conserved nicotinamide adenine dinucleotide-dependent lysine deacetylases/deacylases that regulate fundamental biological processes including aging. In this study, we reveal that male Sirt7 knockout (KO) mice exhibited an extension of mean and maximum lifespan and a delay in the age-associated mortality rate. In addition, aged male Sirt7 KO mice displayed better glucose tolerance with improved insulin sensitivity compared with wild-type (WT) mice. Fibroblast growth factor 21 (FGF21) enhances insulin sensitivity and extends lifespan when it is overexpressed. Serum levels of FGF21 were markedly decreased with aging in WT mice. In contrast, this decrease was suppressed in Sirt7 KO mice, and the serum FGF21 levels of aged male Sirt7 KO mice were higher than those of WT mice. Activating transcription factor 4 (ATF4) stimulates Fgf21 transcription, and the hepatic levels of Atf4 mRNA were increased in aged male Sirt7 KO mice compared with WT mice. Our findings indicate that the loss of SIRT7 extends lifespan and improves glucose metabolism in male mice. High serum FGF21 levels might be involved in the beneficial effect of SIRT7 deficiency.
Molar loss induces hypothalamic and hippocampal astrogliosis in aged mice. 国際誌査読有り

Masae Furukawa, Hirobumi Tada, Jingshu Wang, Mitsuyoshi Yamada, Mie Kurosawa, Akiko Satoh, Noboru Ogiso, Yosuke Shikama, Kenji Matsushita

Scientific reports　12　(1)　6409-6409　2022年4月18日

DOI： 10.1038/s41598-022-10321-w 　

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Age-related tooth loss impedes mastication. Epidemiological and physiological studies have reported that poor oral hygiene and occlusion are associated with cognitive decline. In the present study, we analyzed the mechanism by which decreased occlusal support following bilateral extraction of the maxillary first molars affects cognitive functions in young and aged mice and examined the expression of brain-function-related genes in the hippocampus and hypothalamus. We observed decreased working memory, enhanced restlessness, and increased nocturnal activity in aged mice with molar extraction compared with that in mice with intact molars. Furthermore, in the hypothalamus and hippocampus of molar-extracted aged mice, the transcript-level expression of Bdnf, Rbfox3, and Fos decreased, while that of Cdkn2a and Aif1 increased. Thus, decreased occlusal support after maxillary first molar extraction may affect cognitive function and activity in mice by influencing aging, neural activity, and neuroinflammation in the hippocampus and hypothalamus.
Hypothalamic orexin and mechanistic target of rapamycin activation mediate sleep dysfunction in a mouse model of tuberous sclerosis complex. 国際誌査読有り

Bo Zhang, Dongjun Guo, Lirong Han, Nicholas Rensing, Akiko Satoh, Michael Wong

Neurobiology of disease　134　104615-104615　2020年2月

DOI： 10.1016/j.nbd.2019.104615 　

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Tuberous sclerosis complex (TSC) is a genetic disease related to hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and manifested by neurological symptoms, such as epilepsy and sleep disorders. The pathophysiology of sleep dysfunction is poorly understood and is likely multifactorial, but may involve intrinsic biological regulators in the brain. Here, we characterized a mouse model of sleep disorders in TSC and investigated mechanisms of sleep dysfunction in this conditional knockout model involving inactivation of the Tsc1 gene in neurons and astrocytes (Tsc1GFAPCKO mice). Sleep studies utilizing EEG, EMG, and behavioral analysis found that Tsc1GFAPCKO mice have decreased REM sleep and impaired sleep-wake differentiation between light and dark phases. mTOR activity and orexin expression were increased in hypothalamic sections and cultured hypothalamic neurons from Tsc1GFAPCKO mice. Both the sleep abnormalities and increased orexin expression in Tsc1GFAPCKO mice were reversed by rapamycin treatment, indicating their dependence on mTOR activation. An orexin antagonist, suvorexant, also restored normal REM levels in Tsc1GFAPCKO mice. These results identify a novel mechanistic link between mTOR and orexin in the hypothalamus related to sleep dysfunction and suggest a targeted therapeutic approach to sleep disorders in TSC.
Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice. 国際誌査読有り

Mitsukuni Yoshida, Akiko Satoh, Jonathan B Lin, Kathryn F Mills, Yo Sasaki, Nicholas Rensing, Michael Wong, Rajendra S Apte, Shin-Ichiro Imai

Cell metabolism　30　(2)　329-342　2019年8月6日

DOI： 10.1016/j.cmet.2019.05.015 　

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Aging is a significant risk factor for impaired tissue functions and chronic diseases. Age-associated decline in systemic NAD+ availability plays a critical role in regulating the aging process across many species. Here, we show that the circulating levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) significantly decline with age in mice and humans. Increasing circulating eNAMPT levels in aged mice by adipose-tissue-specific overexpression of NAMPT increases NAD+ levels in multiple tissues, thereby enhancing their functions and extending healthspan in female mice. Interestingly, eNAMPT is carried in extracellular vesicles (EVs) through systemic circulation in mice and humans. EV-contained eNAMPT is internalized into cells and enhances NAD+ biosynthesis. Supplementing eNAMPT-containing EVs isolated from young mice significantly improves wheel-running activity and extends lifespan in aged mice. Our findings have revealed a novel EV-mediated delivery mechanism for eNAMPT, which promotes systemic NAD+ biosynthesis and counteracts aging, suggesting a potential avenue for anti-aging intervention in humans.
Roles of tau pathology in the locus coeruleus (LC) in age-associated pathophysiology and Alzheimer's disease pathogenesis: Potential strategies to protect the LC against aging. 国際誌招待有り査読有り

Akiko Satoh, Koichi M Iijima

Brain research　1702　17-28　2019年1月1日

DOI： 10.1016/j.brainres.2017.12.027 　

ISSN：0006-8993

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The locus coeruleus (LC) is the noradrenaline (norepinephrine, NE)-containing nucleus in the brainstem and innervates into widespread brain regions. This LC-NE system plays a critical role in a variety of brain functions, including attention, arousal, emotion, cognition, and the sleep-wake cycle. The LC is one of the brain regions vulnerable to the occurrence of neurofibrillary tangles (NFTs), which is associated with "primary age-related tauopathy (PART)" that describes the pathology commonly observed in the brains of aged individuals. In Alzheimer's disease (AD), the LC is one of the first places to develop NFTs, which may act as a seed for subsequent spreading of the pathology throughout the brain upon amyloid-β (Aβ) accumulation. As AD progresses, significant neuron loss occurs in the LC. Moreover, LC neurodegeneration is not only a consequence of AD, but also drives clinical and pathological manifestations of AD, such as microglial dysregulation, sleep disturbance, cognitive decline, and neurovascular dysfunction. Therefore, prevention of NFT pathology and neuron loss in the LC-NE system is critical for suppressing the progression of AD. We propose that targeting aging itself may be a proactive intervention against age-associated changes in the LC. Such an approach could open the way for novel interventions against age-associated neurodegenerative disorders, in particular, AD.
Hypothalamic Sirt1 protects terminal Schwann cells and neuromuscular junctions from age-related morphological changes. 国際誌査読有り

Alison K Snyder-Warwick, Akiko Satoh, Katherine B Santosa, Shin-Ichiro Imai, Albina Jablonka-Shariff

Aging cell　17　(4)　e12776　2018年8月

DOI： 10.1111/acel.12776 　

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Neuromuscular decline occurs with aging. The neuromuscular junction (NMJ), the interface between motor nerve and muscle, also undergoes age-related changes. Aging effects on the NMJ components-motor nerve terminal, acetylcholine receptors (AChRs), and nonmyelinating terminal Schwann cells (tSCs)-have not been comprehensively evaluated. Sirtuins delay mammalian aging and increase longevity. Increased hypothalamic Sirt1 expression results in more youthful physiology, but the relationship between NMJ morphology and hypothalamic Sirt1 was previously unknown. In wild-type mice, all NMJ components showed age-associated morphological changes with ~80% of NMJs displaying abnormalities by 17 months of age. Aged mice with brain-specific Sirt1 overexpression (BRASTO) had more youthful NMJ morphologic features compared to controls with increased tSC numbers, increased NMJ innervation, and increased numbers of normal AChRs. Sympathetic NMJ innervation was increased in BRASTO mice. In contrast, hypothalamic-specific Sirt1 knockdown led to tSC abnormalities, decreased tSC numbers, and more denervated endplates compared to controls. Our data suggest that hypothalamic Sirt1 functions to protect NMJs in skeletal muscle from age-related changes via sympathetic innervation.
The brain, sirtuins, and ageing 査読有り

Akiko Satoh, Shin-ichiro Imai, Leonard Guarente

NATURE REVIEWS NEUROSCIENCE　18　(6)　362-374　2017年6月

DOI： 10.1038/nrn.2017.42 　

ISSN：1471-003X

eISSN：1471-0048
Deficiency of Prdm13, a dorsomedial hypothalamus-enriched gene, mimics age-associated changes in sleep quality and adiposity 査読有り

Akiko Satoh, Cynthia S. Brace, Nick Rensing, Shin-ichiro Imai

AGING CELL　14　(2)　209-218　2015年4月

DOI： 10.1111/acel.12299 　

ISSN：1474-9718

eISSN：1474-9726
Systemic regulation of mammalian ageing and longevity by brain sirtuins 査読有り

Akiko Satoh, Shin-ichiro Imai

NATURE COMMUNICATIONS　5　4211　2014年6月

DOI： 10.1038/ncomms5211 　

ISSN：2041-1723
Hypothalamic Sirt1 in aging 査読有り

Akiko Satoh, Shin-ichiro Imai

AGING-US　6　(1)　1-2　2014年1月

DOI： 10.18632/aging.100627 　

ISSN：1945-4589
Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. 国際誌

Akiko Satoh, Cynthia S Brace, Nick Rensing, Paul Cliften, David F Wozniak, Erik D Herzog, Kelvin A Yamada, Shin-Ichiro Imai

Cell metabolism　18　(3)　416-30　2013年9月3日

DOI： 10.1016/j.cmet.2013.07.013 　

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The mammalian Sir2 ortholog Sirt1 plays an important role in metabolic regulation. However, the role of Sirt1 in the regulation of aging and longevity is still controversial. Here we demonstrate that brain-specific Sirt1-overexpressing (BRASTO) transgenic mice show significant life span extension in both males and females, and aged BRASTO mice exhibit phenotypes consistent with a delay in aging. These phenotypes are mediated by enhanced neural activity specifically in the dorsomedial and lateral hypothalamic nuclei (DMH and LH, respectively), through increased orexin type 2 receptor (Ox2r) expression. We identified Nk2 homeobox 1 (Nkx2-1) as a partner of Sirt1 that upregulates Ox2r transcription and colocalizes with Sirt1 in the DMH and LH. DMH/LH-specific knockdown of Sirt1, Nkx2-1, or Ox2r and DMH-specific Sirt1 overexpression further support the role of Sirt1/Nkx2-1/Ox2r-mediated signaling for longevity-associated phenotypes. Our findings indicate the importance of DMH/LH-predominant Sirt1 activity in the regulation of aging and longevity in mammals.
The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. 国際誌

Akiko Satoh, Liana Stein, Shin Imai

Handbook of experimental pharmacology　206　125-62　2011年

DOI： 10.1007/978-3-642-21631-2_7 　

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Ever since the discovery of sirtuins a decade ago, interest in this family of NAD-dependent deacetylases has exploded, generating multiple lines of evidence implicating sirtuins as evolutionarily conserved regulators of lifespan. In mammals, it has been established that sirtuins regulate physiological responses to metabolism and stress, two key factors that affect the process of aging. Further investigation into the intimate connection among sirtuins, metabolism, and aging has implicated the activation of SIRT1 as both preventative and therapeutic measures against multiple age-associated disorders including type 2 diabetes and Alzheimer's disease. SIRT1 activation has clear potential to not only prevent age-associated diseases but also to extend healthspan and perhaps lifespan. Sirtuin activating compounds and NAD intermediates are two promising ways to achieve these elusive goals.
SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus. 国際誌

Akiko Satoh, Cynthia S Brace, Gal Ben-Josef, Tim West, David F Wozniak, David M Holtzman, Erik D Herzog, Shin-ichiro Imai

The Journal of neuroscience : the official journal of the Society for Neuroscience　30　(30)　10220-32　2010年7月28日

DOI： 10.1523/JNEUROSCI.1385-10.2010 　

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Diet restriction retards aging and extends lifespan by triggering adaptive mechanisms that alter behavioral, physiological, and biochemical responses in mammals. Little is known about the molecular pathways evoking the corresponding central response. One factor that mediates the effects of diet restriction is the mammalian nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1. Here we demonstrate that diet restriction significantly increases SIRT1 protein levels and induces neural activation in the dorsomedial and lateral hypothalamic nuclei. Increasing SIRT1 in the brain of transgenic (BRASTO) mice enhances neural activity specifically in these hypothalamic nuclei, maintains a higher range of body temperature, and promotes physical activity in response to different diet-restricting paradigms. These responses are all abrogated in Sirt1-deficient mice. SIRT1 upregulates expression of the orexin type 2 receptor specifically in these hypothalamic nuclei in response to diet-restricting conditions, augmenting response to ghrelin, a gut hormone whose levels increase in these conditions. Our results suggest that in the hypothalamus, SIRT1 functions as a key mediator of the central response to low nutritional availability, providing insight into the role of the hypothalamus in the regulation of metabolism and aging in mammals.
Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice 査読有り

Kathryn Moynihan Ramsey, Kathryn F. Mills, Akiko Satoh, Shin-ichiro Imai

AGING CELL　7　(1)　78-88　2008年2月

DOI： 10.1111/j.1474-9726.2007.00355.x 　

ISSN：1474-9718
Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme 査読有り

Javier R. Revollo, Antje Koerner, Kathryn F. Mills, Akiko Satoh, Tao Wang, Antje Garten, Biplab Dasgupta, Yo Sasaki, Cynthia Wolberger, R. Reid Townsend, Jeffrey Milbrandt, Wieland Kiess, Shin-Ichiro Imai

CELL METABOLISM　6　(5)　363-375　2007年11月

DOI： 10.1016/j.cmet.2007.09.003 　

ISSN：1550-4131

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MISC 5

加齢に伴う睡眠変化に関与する視床下部神経細胞の同定招待有り

辻将吾, 佐藤亜希子

実験医学　41　(14)　2303-2306　2023年7月

DOI： 10.18958/7323-00003-0000586-00. 　
脳による老化制御とエピジェネティクス招待有り

辻将吾, 佐藤亜希子

Geriatric Medicine　61　29-33　2023年1月
特集抗老化医療の未来をさぐる : 哺乳類における老化・寿命制御の理解とその社会実装序文招待有り

今井眞一郎, 佐藤亜希子

Geriatric Medicine　61　5-7　2023年1月
脳老化と神経変性疾患における細胞老化招待有り

佐藤亜希子

実験医学　40　401-406　2022年
睡眠と脳内の寿命制御因子招待有り

佐藤亜希子

医学のあゆみ　279　356-359　2021年

書籍等出版物 1

Aging Mechanisms II: Longevity, Metabolism, and Brain Aging

2022年4月

講演・口頭発表等 13

マウス全脳網羅的解析による睡眠制限への神経活動応答の評価

漆畑拓弥, 後藤三緒, 壁谷慶子, 清塚麻衣, 丸山栞穂, 辻将吾, 多田敬典, 佐藤亜希子

第４６回日本分子生物学会, 一般演題　2023年12月8日
哺乳類における睡眠覚醒形態老化への視床下部Prdm13陽性神経の役割招待有り

佐藤亜希子

第４６回日本分子生物学会, シンポジウム　2023年12月6日
睡眠調節を介した中枢性老化寿命制御機構招待有り

佐藤亜希子

第３回日本オートファジーコンソーシアム　2023年11月22日
脳は老化寿命制御の中心なのだろうかー哺乳類の中枢性老化寿命制御機構の紹介ー招待有り

佐藤亜希子

第63回生命科学夏の学校生化学若い研究者の会, シンポジウム　2023年8月27日
視床下部による哺乳類の老化寿命制御機構招待有り

佐藤亜希子

DUAL Seminar in Tokai　2023年6月28日
Circulating miR-323a-3p as a novel potential plasma biomarker for multimorbidity burden in middle aged and older adults: results from NILS-LSA in Japan

Wei-Min Chu, Mio Goto, Keiko Kabetani, Yukiko Nishita, Hiroshi Shimokata, Akiko Satoh, Rei Otsuka

IAGG　2023年6月12日
視床下部Prdm13系の老化に伴う睡眠変化における役割招待有り

佐藤亜希子

第22回日本再生医療学会総会シンポジウム　2023年3月25日
睡眠調節を介した視床下部による老化寿命制御機構招待有り

佐藤亜希子

第100回日本生理学会学術総会大会シンポジウム　2023年3月15日
高脂肪食下における背内側部特異的Prdm13欠損が代謝能にもたらす機能変化について

丸山栞穂, 清塚麻衣, 後藤三緒, 壁谷慶子, 辻将吾, 多田敬典, 佐藤亜希子

第100回日本生理学会学術総会大会　2023年3月14日
The role of hypothalamic neurons in sleep, aging and longevity 招待有り

The 17th International Symposium of the Institute Network for Biomedical Sciences　2022年10月13日
睡眠調節を介した老化寿命制御機構について招待有り

佐藤亜希子

レドックスR&D戦略委員会第２回企画シンポジウム　2022年5月13日
Effects of dorsomedial hypothalamus-specific Prdm13 deficiency in brain aging

第159回東北大学加齢医学研究所集談会　2022年2月10日
視床下部神経による睡眠と老化寿命の共通制御メカニズム招待有り

佐藤亜希子

第94回日本生化学会シンポジウム　2021年11月3日

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共同研究・競争的資金等の研究課題 10

Functional Connectivityに着目した新規老化指標の創出

佐藤亜希子, 漆畑拓弥, 領家梨恵

2025年6月27日～ 2029年3月31日
時間生物学に立脚した時間医薬イノベーション

土居雅夫, 佐藤亜希子

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (S)

研究機関：Kyoto University

2022年4月27日～ 2027年3月31日
マルチスケール4D 生物学の創成

片岡直也, 杉拓磨, 別役重之, 佐藤亜希子

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Transformative Research Areas (B)

研究機関：Nagoya University

2023年4月1日～ 2026年3月31日
視床下部Prdm13シグナル系による健康寿命調節機構の解明

佐藤亜希子

2022年4月1日～ 2025年3月31日
アルツハイマー病保護因子APOE２多型の作用機序の解明と治療薬開発への応用

篠原充, 大塚礼, 笹栗弘貴, 齊藤祐子, 西田裕紀子, 佐藤亜希子, 菊地正隆, 小木曽昇

2021年4月1日～ 2025年3月31日

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各APOEノックインマウスの加齢化を進め、定期的な活動量変化とともに生存率を評価した。３年近く長生きする場合があり、まだ最終コホートは生存しているが、結果をまとめつつある。それとともに、CRISPR-CAS9で作製した新規遺伝子組み換えマウスのバッククロスをほぼ終え、解析やADマウスモデルとの交配に着手した。長寿遺伝子APOE2の作用を模倣するであろう薬剤について、生体への投与方法の検討を行った。またオミクス解析も進めた。研究のより詳細な内容や結果については論文発表まで公表を控えたい。
アルツハイマー病保護因子APOE２多型の作用機序の解明と治療薬開発への応用

篠原充, 佐藤亜希子, 笹栗弘貴, 齊藤祐子, 大塚礼, 西田裕紀子, 菊地正隆, 小木曽昇

2021年4月1日～ 2025年3月31日

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各APOEノックインマウスの加齢化を進め、定期的な活動量変化とともに生存率を評価していくとともに、関連する候補分子の測定系や、臨床データ、検体の準備を行った。また新規遺伝子組み換えマウスの作製とともに、長寿遺伝子APOE2の作用を模倣するであろう薬剤の探索や生体への投与方法の検討を行った。研究のより詳細な内容や結果については論文発表まで公表を控えたい。
老化過程において視床下部機能を積極的に維持する分子制御機序

佐藤亜希子

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Challenging Research (Exploratory)

研究機関：National Center for Geriatrics and Gerontology

2020年7月30日～ 2022年3月31日

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本研究では、老化に伴い、脳内では新規因子が生成され、積極的に視床下部の機能を維持しようとする機序があるという可能経緯を検証するために、若齢マウスと比較し老齢マウスの視床下部背内側核で顕著に発現量が増加する遺伝子群の分類と候補遺伝子の選定を行った。候補遺伝子の発現変化を比較し、脳領域特異的な変化と脳全体で変化が認められる群に分類し、神経細胞培養系において細胞生存率に影響を及ぼしうる遺伝子を同定した。
視床下部特異的SIRT1を指標とした脳・口腔相関の解明

山田匡恵, 佐藤亜希子, 松下健二

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：National Center for Geriatrics and Gerontology

2019年4月1日～ 2022年3月31日

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本研究は、臼歯の喪失による咀嚼機能の低下が実験動物の脳、特に、視床下部や海馬への影響について分子生物学的、行動実験学的、免疫組織科学的に検討することである。具体的には、上顎第一臼歯を抜歯した若齢及び老齢マウスを飼育したところ、特に老齢マウスにおいて著しい認知機能の低下、運動機能の低下が確認され、また視床下部や海馬においても、脳内の炎症や老化を示すマーカーが上昇した。このことから、咀嚼機能の低下は脳の老化を誘導し、また認知機能の低下を示すことが明らかとなった。
老化に伴う入眠障害と体温調節能低下を制御する視床下部背内側核の役割

佐藤亜希子

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：National Center for Geriatrics and Gerontology

2018年4月1日～ 2022年3月31日

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本研究では、老化に伴い視床下部背内側核のPRDM13活性が低下すると、入眠時の体温調節機序が破綻し、その結果、睡眠障害がもたらされる可能性を検証した。その結果、老齢マウス、食餌制限マウス、背内側核特異的Prdm13ノックアウトマウスの解析から、入眠潜時の変化とともに認められる体温変化や睡眠制限後の自由睡眠時に認められる体温変化には、視床下部神経の睡眠調節機構の変化が関与していることが示唆された。また、作用の強さには性差があることが明らかとなった。
視床下部Prdm13の老化及び睡眠制御メカニズムの解明

佐藤亜希子

2017年8月25日～ 2019年3月31日

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本研究の主な目的は、老化に伴う視床下部の機能低下の役割を明らかにすることである。睡眠の質的低下が全身の生理学的機能に悪影響を及ぼし、その結果、老年性疾患の発症に繋がる、という知見が報告されている。しかしながら、睡眠の質がなぜ老化に伴い低下するのか、睡眠の質的低下が全身性の老化現象をどのように引き起こすのか、その詳細な分子制御機序については明らかにされていない。これまでに研究代表者は、視床下部背内側核が老化・寿命を制御する上で重要な役割を果たしていることを明らかにした。また、視床下部背内側核に発現しているPR domain-containing protein 13 (Prdm13)が睡眠の質的変化を調節していることを見出した。本年度までに、Prdm13ノックダウンマウスの睡眠制御メカニズムを明らかにするために、睡眠制限に対する反応性や概日周期行動の解析を実施した。現在も、Prdm13ノックアウトマウスを作製し、解析を続けている。

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