Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition.
Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition.
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Hochuekkito通过营养不良的老年小鼠通过Sirtuin 1恢复了肝线粒体代谢功能的下降。
DOI：
10.3389/fphys.2022.848960
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发表时间：
2022
影响因子：
4
通讯作者：
Takeda H
中科院分区：
文献类型：
--
作者：
Nahata M;Fujitsuka N;Sekine H;Shimobori C;Ohbuchi K;Iizuka S;Mogami S;Ohnishi S;Takeda H
营养不良影响基本的日常活动，导致身体虚弱，与年轻人相比，老年人的情况更为严重。众所周知，老年人更容易受到代谢压力的影响。因此，在本研究中，我们使用限食（FR）小鼠，旨在评估衰老对运动活动和肝脏代谢功能的影响。此外，我们还研究了肝线粒体在衰老过程中肝脏代谢功能的参与，以及日本传统药物hochuekkito （HET）的治疗效果。我们的研究结果表明，在限制食物摄取量的30%并持续5天后，23 - 26月龄（老年）小鼠的运动活动低于9周龄（年轻）小鼠。此外，与年轻小鼠相比，老年小鼠表现出与尿素循环、线粒体功能和抗氧化应激相关的代谢物水平显著降低。老年小鼠的肝脏线粒体DNA拷贝数也比年轻小鼠减少得更多。此外，衰老小鼠sirtuin 1 （SIRT1）和线粒体生物发生相关调节因子的基因表达水平减弱。然而，HET治疗部分恢复了这些变化，也改善了运动活动，并且与丙氨酸联合治疗在这方面产生了更显著的效果。因此，我们的研究结果表明，老年FR小鼠运动活动的下降与肝脏线粒体代谢功能的下降有关，其途径是SIRT1表达的下降，而SIRT1表达的下降通过HET治疗得以恢复。这表明增强肝脏线粒体的代谢功能有助于缓解老年人的能量缺乏。
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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影响因子：
5.6
作者：
Kumar R;Reichert AS
通讯作者：
Reichert AS
影响因子：
25.7
作者：
Davuluri G;Krokowski D;Guan BJ;Kumar A;Thapaliya S;Singh D;Hatzoglou M;Dasarathy S
通讯作者：
Dasarathy S
影响因子：
6.3
作者：
Cederholm, T.;Barazzoni, R.;Singer, P.
通讯作者：
Singer, P.
影响因子：
11
作者：
Fujitsuka, N.;Asakawa, A.;Morinaga, A.;Amitani, M. S.;Amitani, H.;Katsuura, G.;Sawada, Y.;Sudo, Y.;Uezono, Y.;Mochiki, E.;Sakata, I.;Sakai, T.;Hanazaki, K.;Yada, T.;Yakabi, K.;Sakuma, E.;Ueki, T.;Niijima, A.;Nakagawa, K.;Okubo, N.;Takeda, H.;Asaka, M.;Inui, A.
通讯作者：
Inui, A.
影响因子：
5.9
作者：
Cai, Mudan;Yang, Eun Jin
通讯作者：
Yang, Eun Jin