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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #386626

Research Project: Impact of Maternal Influence and Early Dietary Factors on Child Growth, Development, and Metabolic Health

Location: Arkansas Children's Nutrition Center

Title: Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling

Author
item BOSE, CHHANDA - Texas Tech University Health Science Center
item ALVES, INES - University Of Coimbra
item SINGH, PREETI - University Arkansas For Medical Sciences (UAMS)
item PALADE, PHILIP - University Arkansas For Medical Sciences (UAMS)
item CARVALHO, EUGENIA - Arkansas Children'S Nutrition Research Center (ACNC)
item BORSHEIM, ELISABET - Arkansas Children'S Nutrition Research Center (ACNC)
item JUN, SE-RAN - University Arkansas For Medical Sciences (UAMS)
item CHEEMA, AMRITA - Georgetown University Medical Center
item BOERMA, MARJAN - University Arkansas For Medical Sciences (UAMS)
item AWASTHI, SANJAY - Texas Tech University Health Science Center
item SINGH, SHARDA - Texas Tech University Health Science Center

Submitted to: Aging Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/30/2020
Publication Date: 10/17/2020
Citation: Bose, C., Alves, I., Singh, P., Palade, P.T., Carvalho, E., Borsheim, E., Jun, S., Cheema, A., Boerma, M., Awasthi, S., Singh, S.P. 2020. Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling. Aging Cell. 19:e13261. https://doi.org/10.1111/acel.13261.
DOI: https://doi.org/10.1111/acel.13261

Interpretive Summary: During aging, gradual dysfunction of mitochondria (the powerhouses of the cells) and resulting oxidative damage are commonly observed. This may be related to multiple health problems including loss of muscle mass and cardiovascular disease. Nrf2 (nuclear factor erythroid 2–related factor 2) is an important molecule that regulate antioxidant and protective genes. Nrf2 is activated in response to oxidative stress. Sulforaphane (SFN) is a compound found in cruciferous vegetables like broccoli, bok choy, and cabbage. SFN can activate Nrf2 and several studies have shown promising effects of SFN on CVD risk factors. This study aimed to determine whether SFN can prevent age-related loss of function in the heart and skeletal muscle. Mice that were 2-month-old or 21-22 month-old were given regular rodent diet or diet supplemented with SFN for 12 weeks. At the end of the study, skeletal muscle and heart function, mitochondrial function, and Nrf2 activity were measured. The results showed that older had lower Nrf2 activity and mitochondrial function, together with a lower skeletal muscle mass and cardiac function compared to young mice. In the old mice, SFN restored Nrf2 activity, mitochondrial function, cardiac function, capacity to exercise, handling of sugar, and activation of skeletal muscle satellite cells (important for renewal of the muscle cells). Our results suggest that the age-associated decline in Nrf2 signaling activity and the associated mitochondrial dysfunction might be related to the development of age-related disease processes. Therefore, the restoration of Nrf2 activity by SFN may be a safe and effective strategy to protect against muscle and heart dysfunction due to aging.

Technical Abstract: 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 in-sulin 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.