Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling
| Autor: | Inês N Alves, Chhanda Bose, Elisabet Børsheim, Marjan Boerma, Eugenia Carvalho, Amrita K. Cheema, Sharda P Singh, Philip Palade, Se-Ran Jun, Preeti Singh, Sanjay Awasthi |
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| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cardiac function curve Male Aging medicine.medical_specialty Sarcopenia Sarcopenia / pathology NF-E2-Related Factor 2 cardiac functions Sulfoxides / pharmacology Isothiocyanates / therapeutic use Biology medicine.disease_cause Nrf2 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Insulin resistance Sulfoxides / therapeutic use Isothiocyanates Internal medicine mitochondrial dysfunction medicine Animals Myopathy Loss function Cardiac functions Original Paper Skeletal muscle Cell Biology Original Articles medicine.disease Oxidative Stress 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Sulfoxides NF-E2-Related Factor 2 / metabolism medicine.symptom Isothiocyanates / pharmacology Mitochondrial dysfunction Sulforaphane 030217 neurology & neurosurgery Oxidative stress Signal Transduction |
| Zdroj: | Aging Cell |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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