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

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, decrea...

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Autores principales:	Miwa Nahata, Sachiko Mogami, Hitomi Sekine, Seiichi Iizuka, Naoto Okubo, Naoki Fujitsuka, Hiroshi Takeda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/2976f3861c604a40a8c972724066b04e
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spelling	oai:doaj.org-article:2976f3861c604a40a8c972724066b04e2021-12-02T18:18:31ZBcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito10.1038/s41514-021-00065-82056-3973https://doaj.org/article/2976f3861c604a40a8c972724066b04e2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00065-8https://doaj.org/toc/2056-3973Abstract 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.Miwa NahataSachiko MogamiHitomi SekineSeiichi IizukaNaoto OkuboNaoki FujitsukaHiroshi TakedaNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Miwa Nahata Sachiko Mogami Hitomi Sekine Seiichi Iizuka Naoto Okubo Naoki Fujitsuka Hiroshi Takeda Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
description	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.
format	article
author	Miwa Nahata Sachiko Mogami Hitomi Sekine Seiichi Iizuka Naoto Okubo Naoki Fujitsuka Hiroshi Takeda
author_facet	Miwa Nahata Sachiko Mogami Hitomi Sekine Seiichi Iizuka Naoto Okubo Naoki Fujitsuka Hiroshi Takeda
author_sort	Miwa Nahata
title	Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
title_short	Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
title_full	Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
title_fullStr	Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
title_full_unstemmed	Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
title_sort	bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2976f3861c604a40a8c972724066b04e
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Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito

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