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Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition

Malnutrition impairs basic daily activities and leads to physical frailty, which is aggravated in the elderly compared with young adults. It is also well-known that the elderly are more vulnerable to metabolic stress. Therefore, in this study, using a food restricted (FR) mouse, we aimed to evaluate...

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Autores principales: Nahata, Miwa, Fujitsuka, Naoki, Sekine, Hitomi, Shimobori, Chika, Ohbuchi, Katsuya, Iizuka, Seiichi, Mogami, Sachiko, Ohnishi, Shunsuke, Takeda, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921682/
https://www.ncbi.nlm.nih.gov/pubmed/35299665
http://dx.doi.org/10.3389/fphys.2022.848960
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author Nahata, Miwa
Fujitsuka, Naoki
Sekine, Hitomi
Shimobori, Chika
Ohbuchi, Katsuya
Iizuka, Seiichi
Mogami, Sachiko
Ohnishi, Shunsuke
Takeda, Hiroshi
author_facet Nahata, Miwa
Fujitsuka, Naoki
Sekine, Hitomi
Shimobori, Chika
Ohbuchi, Katsuya
Iizuka, Seiichi
Mogami, Sachiko
Ohnishi, Shunsuke
Takeda, Hiroshi
author_sort Nahata, Miwa
collection PubMed
description Malnutrition impairs basic daily activities and leads to physical frailty, which is aggravated in the elderly compared with young adults. It is also well-known that the elderly are more vulnerable to metabolic stress. Therefore, in this study, using a food restricted (FR) mouse, we aimed to evaluate the effect of aging on locomotor activity and liver metabolic function. Further, we also investigated the involvement of hepatic mitochondria in liver metabolic function during aging, as well as the therapeutic benefit of the traditional Japanese medicine, hochuekkito (HET). Our findings indicated that following food restriction provided as 30% of ad libitum intake for 5 days, the locomotor activity was lower in 23–26-month-old (aged) mice than in 9-week-old (young) mice. Further, compared with young mice, aged mice exhibited significant decreases in the levels of metabolites related to the urea cycle, mitochondrial function, and anti-oxidative stress. The livers of the aged mice also showed a greater decrease in mitochondrial DNA copy number than young mice. Furthermore, the gene expression levels of sirtuin 1 (SIRT1) and mitochondrial biogenesis-related regulators were attenuated in aged mice. However, these changes were partially restored by HET treatment, which also improved locomotor activity, and combined treatment with alanine resulted in more significant effects in this regard. Therefore, our findings suggested that the decrease in locomotor activity in aged FR mice was associated with a decline in the metabolic function of hepatic mitochondria via decreased SIRT1 expression, which was restored by HET treatment. This implies that enhancing the metabolic function of liver mitochondria can contribute to alleviating energy deficiency in the elderly.
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spelling pubmed-89216822022-03-16 Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition Nahata, Miwa Fujitsuka, Naoki Sekine, Hitomi Shimobori, Chika Ohbuchi, Katsuya Iizuka, Seiichi Mogami, Sachiko Ohnishi, Shunsuke Takeda, Hiroshi Front Physiol Physiology Malnutrition impairs basic daily activities and leads to physical frailty, which is aggravated in the elderly compared with young adults. It is also well-known that the elderly are more vulnerable to metabolic stress. Therefore, in this study, using a food restricted (FR) mouse, we aimed to evaluate the effect of aging on locomotor activity and liver metabolic function. Further, we also investigated the involvement of hepatic mitochondria in liver metabolic function during aging, as well as the therapeutic benefit of the traditional Japanese medicine, hochuekkito (HET). Our findings indicated that following food restriction provided as 30% of ad libitum intake for 5 days, the locomotor activity was lower in 23–26-month-old (aged) mice than in 9-week-old (young) mice. Further, compared with young mice, aged mice exhibited significant decreases in the levels of metabolites related to the urea cycle, mitochondrial function, and anti-oxidative stress. The livers of the aged mice also showed a greater decrease in mitochondrial DNA copy number than young mice. Furthermore, the gene expression levels of sirtuin 1 (SIRT1) and mitochondrial biogenesis-related regulators were attenuated in aged mice. However, these changes were partially restored by HET treatment, which also improved locomotor activity, and combined treatment with alanine resulted in more significant effects in this regard. Therefore, our findings suggested that the decrease in locomotor activity in aged FR mice was associated with a decline in the metabolic function of hepatic mitochondria via decreased SIRT1 expression, which was restored by HET treatment. This implies that enhancing the metabolic function of liver mitochondria can contribute to alleviating energy deficiency in the elderly. Frontiers Media S.A. 2022-03-01 /pmc/articles/PMC8921682/ /pubmed/35299665 http://dx.doi.org/10.3389/fphys.2022.848960 Text en Copyright © 2022 Nahata, Fujitsuka, Sekine, Shimobori, Ohbuchi, Iizuka, Mogami, Ohnishi and Takeda. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Nahata, Miwa
Fujitsuka, Naoki
Sekine, Hitomi
Shimobori, Chika
Ohbuchi, Katsuya
Iizuka, Seiichi
Mogami, Sachiko
Ohnishi, Shunsuke
Takeda, Hiroshi
Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition
title Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition
title_full Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition
title_fullStr Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition
title_full_unstemmed Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition
title_short Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition
title_sort decline in liver mitochondria metabolic function is restored by hochuekkito through sirtuin 1 in aged mice with malnutrition
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921682/
https://www.ncbi.nlm.nih.gov/pubmed/35299665
http://dx.doi.org/10.3389/fphys.2022.848960
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