Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling.
Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling.
复制标题
Sulforaphane通过NRF2信号传导可防止与年龄相关的心脏和肌肉功能障碍。
DOI：
10.1111/acel.13261
复制
发表时间：
2020-11
期刊：
影响因子：
7.8
通讯作者：
Singh SP
中科院分区：
文献类型：
--
作者：
Bose C;Alves I;Singh P;Palade PT;Carvalho E;Børsheim E;Jun SR;Cheema A;Boerma M;Awasthi S;Singh SP
Scheme depicts hypothesized decreases of heart and SKM function during aging via ROS and partial reversal by SFN activation of Nrf2 that results in significant restoration of function of both types of muscle. A decline in heart and skeletal muscle function was observed in aged mice, with altered mitochondrial structure and gene expression, accompnied by decreases in mitochondrial complex activity, Nrf2 binding to antioxidant‐responsive DNA elements and physical endurance. The addition of sulforaphane (SFN) to the diet improved these age‐related changes in older mice to levels observed in younger ones. We demonstrated in this paper that SFN alleviates age‐associated oxidative damage and improves mitochondrial and cardiac function as well as physical endurance in old mice. Age‐associated mitochondrial dysfunction and oxidative damage are primary causes for multiple health problems including sarcopenia and cardiovascular disease (CVD). Though the role of Nrf2, a transcription factor that regulates cytoprotective gene expression, in myopathy remains poorly defined, it has shown beneficial properties in both sarcopenia and CVD. Sulforaphane (SFN), a natural compound Nrf2‐related activator of cytoprotective genes, provides protection in several disease states including CVD and is in various stages of clinical trials, from cancer prevention to reducing insulin resistance. This study aimed to determine whether SFN may prevent age‐related loss of function in the heart and skeletal muscle. Cohorts of 2‐month‐old and 21‐ to 22‐month‐old mice were administered regular rodent diet or diet supplemented with SFN for 12 weeks. At the completion of the study, skeletal muscle and heart function, mitochondrial function, and Nrf2 activity were measured. Our studies revealed a significant drop in Nrf2 activity and mitochondrial functions, together with a loss of skeletal muscle and cardiac function in the old control mice compared to the younger age group. In the old mice, SFN restored Nrf2 activity, mitochondrial function, cardiac function, exercise capacity, glucose tolerance, and activation/differentiation of skeletal muscle satellite cells. Our results suggest that the age‐associated decline in Nrf2 signaling activity and the associated mitochondrial dysfunction might be implicated in the development of age‐related disease processes. Therefore, the restoration of Nrf2 activity and endogenous cytoprotective mechanisms by SFN may be a safe and effective strategy to protect against muscle and heart dysfunction due to aging.
Scheme depicts hypothesized decreases of heart and SKM function during aging via ROS and partial reversal by SFN activation of Nrf2 that results in significant restoration of function of both types of muscle. A decline in heart and skeletal muscle function was observed in aged mice, with altered mitochondrial structure and gene expression, accompnied by decreases in mitochondrial complex activity, Nrf2 binding to antioxidant‐responsive DNA elements and physical endurance. The addition of sulforaphane (SFN) to the diet improved these age‐related changes in older mice to levels observed in younger ones. We demonstrated in this paper that SFN alleviates age‐associated oxidative damage and improves mitochondrial and cardiac function as well as physical endurance in old mice. Age‐associated mitochondrial dysfunction and oxidative damage are primary causes for multiple health problems including sarcopenia and cardiovascular disease (CVD). Though the role of Nrf2, a transcription factor that regulates cytoprotective gene expression, in myopathy remains poorly defined, it has shown beneficial properties in both sarcopenia and CVD. Sulforaphane (SFN), a natural compound Nrf2‐related activator of cytoprotective genes, provides protection in several disease states including CVD and is in various stages of clinical trials, from cancer prevention to reducing insulin resistance. This study aimed to determine whether SFN may prevent age‐related loss of function in the heart and skeletal muscle. Cohorts of 2‐month‐old and 21‐ to 22‐month‐old mice were administered regular rodent diet or diet supplemented with SFN for 12 weeks. At the completion of the study, skeletal muscle and heart function, mitochondrial function, and Nrf2 activity were measured. Our studies revealed a significant drop in Nrf2 activity and mitochondrial functions, together with a loss of skeletal muscle and cardiac function in the old control mice compared to the younger age group. In the old mice, SFN restored Nrf2 activity, mitochondrial function, cardiac function, exercise capacity, glucose tolerance, and activation/differentiation of skeletal muscle satellite cells. Our results suggest that the age‐associated decline in Nrf2 signaling activity and the associated mitochondrial dysfunction might be implicated in the development of age‐related disease processes. Therefore, the restoration of Nrf2 activity and endogenous cytoprotective mechanisms by SFN may be a safe and effective strategy to protect against muscle and heart dysfunction due to aging.
登录
查看更多内容
DOI：
10.1093/gerona/gly139
发表时间：
2019-03-14
期刊：
The journals of gerontology. Series A, Biological sciences and medical sciences
影响因子：
--
作者：
de Lucia C;Wallner M;Eaton DM;Zhao H;Houser SR;Koch WJ
通讯作者：
Koch WJ
DOI：
10.1186/2046-2395-3-6
发表时间：
2014
期刊：
Longevity & healthspan
影响因子：
--
作者：
Dai DF;Chiao YA;Marcinek DJ;Szeto HH;Rabinovitch PS
通讯作者：
Rabinovitch PS
影响因子：
4.8
作者：
Handschin, Christoph;Chin, Sherry;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.1016/j.mrrev.2016.07.003
发表时间：
2016-10
期刊：
Mutation research. Reviews in mutation research
影响因子：
--
作者：
Boerma M;Sridharan V;Mao XW;Nelson GA;Cheema AK;Koturbash I;Singh SP;Tackett AJ;Hauer-Jensen M
通讯作者：
Hauer-Jensen M
DOI：
10.3390/antiox7080102
发表时间：
2018-07-30
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Barrera G;Pizzimenti S;Daga M;Dianzani C;Arcaro A;Cetrangolo GP;Giordano G;Cucci MA;Graf M;Gentile F
通讯作者：
Gentile F