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Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito

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Title: Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
Authors: Nahata, Miwa Browse this author
Mogami, Sachiko Browse this author
Sekine, Hitomi Browse this author
Iizuka, Seiichi Browse this author
Okubo, Naoto Browse this author →KAKEN DB
Fujitsuka, Naoki Browse this author
Takeda, Hiroshi Browse this author →KAKEN DB
Issue Date: 1-Jul-2021
Publisher: Nature Research
Journal Title: npj Aging and Mechanisms of Disease
Volume: 7
Start Page: 13
Publisher DOI: 10.1038/s41514-021-00065-8
Abstract: Chronic undernutrition contributes to the increase in frailty observed among elderly adults, which is a pressing issue in the sector of health care for older people worldwide. Autophagy, an intracellular recycling system, is closely associated with age-related pathologies. Therefore, decreased autophagy in aging could be involved in the disruption of energy homeostasis that occurs during undernutrition; however, the physiological mechanisms underlying this process remain unknown. Here, we showed that 70% daily food restriction (FR) induced fatal hypoglycemia in 23-26-month-old (aged) mice, which exhibited significantly lower hepatic autophagy than 9-week-old (young) mice. The liver expressions of Bcl-2, an autophagy-negative regulator, and Beclin1-Bcl-2 binding, were increased in aged mice compared with young mice. The autophagy inducer Tat-Beclin1 D11, not the mTOR inhibitor rapamycin, decreased the plasma levels of the glucogenic amino acid and restored the blood glucose levels in aged FR mice. Decreased liver gluconeogenesis, body temperature, physical activity, amino acid metabolism, and hepatic mitochondrial dynamics were observed in the aged FR mice. These changes were restored by treatment with hochuekkito that is a herbal formula containing several autophagy-activating ingredients. Our results indicate that Bcl-2 upregulation in the liver during the aging process disturbs autophagy activation, which increases the vulnerability to undernutrition. The promotion of liver autophagy may offer clinical therapeutic benefits to frail elderly patients.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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