Tags

Type your tag names separated by a space and hit enter

Nobiletin fortifies mitochondrial respiration in skeletal muscle to promote healthy aging against metabolic challenge.
Nat Commun. 2019 08 28; 10(1):3923.NC

Abstract

Circadian disruption aggravates age-related decline and mortality. However, it remains unclear whether circadian enhancement can retard aging in mammals. We previously reported that the small molecule Nobiletin (NOB) activates ROR (retinoid acid receptor-related orphan receptor) nuclear receptors to potentiate circadian oscillation and protect against metabolic dysfunctions. Here we show that NOB significantly improves metabolic fitness in naturally aged mice fed with a regular diet (RD). Furthermore, NOB enhances healthy aging in mice fed with a high-fat diet (HF). In HF skeletal muscle, the NOB-ROR axis broadly activates genes for mitochondrial respiratory chain complexes (MRCs) and fortifies MRC activity and architecture, including Complex II activation and supercomplex formation. These mechanisms coordinately lead to a dichotomous mitochondrial optimization, namely increased ATP production and reduced ROS levels. Together, our study illustrates a focal mechanism by a clock-targeting pharmacological agent to optimize skeletal muscle mitochondrial respiration and promote healthy aging in metabolically stressed mammals.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, 80045, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, 77843, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida, 32610-0274, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, 80045, USA.Department of Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75390, USA.Department of Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75390, USA. Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA.Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, Texas, 77030, USA. Zheng.chen.1@uth.tmc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31462679

Citation

Nohara, Kazunari, et al. "Nobiletin Fortifies Mitochondrial Respiration in Skeletal Muscle to Promote Healthy Aging Against Metabolic Challenge." Nature Communications, vol. 10, no. 1, 2019, p. 3923.
Nohara K, Mallampalli V, Nemkov T, et al. Nobiletin fortifies mitochondrial respiration in skeletal muscle to promote healthy aging against metabolic challenge. Nat Commun. 2019;10(1):3923.
Nohara, K., Mallampalli, V., Nemkov, T., Wirianto, M., Yang, J., Ye, Y., Sun, Y., Han, L., Esser, K. A., Mileykovskaya, E., D'Alessandro, A., Green, C. B., Takahashi, J. S., Dowhan, W., Yoo, S. H., & Chen, Z. (2019). Nobiletin fortifies mitochondrial respiration in skeletal muscle to promote healthy aging against metabolic challenge. Nature Communications, 10(1), 3923. https://doi.org/10.1038/s41467-019-11926-y
Nohara K, et al. Nobiletin Fortifies Mitochondrial Respiration in Skeletal Muscle to Promote Healthy Aging Against Metabolic Challenge. Nat Commun. 2019 08 28;10(1):3923. PubMed PMID: 31462679.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nobiletin fortifies mitochondrial respiration in skeletal muscle to promote healthy aging against metabolic challenge. AU - Nohara,Kazunari, AU - Mallampalli,Venkata, AU - Nemkov,Travis, AU - Wirianto,Marvin, AU - Yang,Jiah, AU - Ye,Youqiong, AU - Sun,Yuxiang, AU - Han,Leng, AU - Esser,Karyn A, AU - Mileykovskaya,Eugenia, AU - D'Alessandro,Angelo, AU - Green,Carla B, AU - Takahashi,Joseph S, AU - Dowhan,William, AU - Yoo,Seung-Hee, AU - Chen,Zheng, Y1 - 2019/08/28/ PY - 2018/08/24/received PY - 2019/08/13/accepted PY - 2019/8/30/entrez PY - 2019/8/30/pubmed PY - 2019/12/25/medline SP - 3923 EP - 3923 JF - Nature communications JO - Nat Commun VL - 10 IS - 1 N2 - Circadian disruption aggravates age-related decline and mortality. However, it remains unclear whether circadian enhancement can retard aging in mammals. We previously reported that the small molecule Nobiletin (NOB) activates ROR (retinoid acid receptor-related orphan receptor) nuclear receptors to potentiate circadian oscillation and protect against metabolic dysfunctions. Here we show that NOB significantly improves metabolic fitness in naturally aged mice fed with a regular diet (RD). Furthermore, NOB enhances healthy aging in mice fed with a high-fat diet (HF). In HF skeletal muscle, the NOB-ROR axis broadly activates genes for mitochondrial respiratory chain complexes (MRCs) and fortifies MRC activity and architecture, including Complex II activation and supercomplex formation. These mechanisms coordinately lead to a dichotomous mitochondrial optimization, namely increased ATP production and reduced ROS levels. Together, our study illustrates a focal mechanism by a clock-targeting pharmacological agent to optimize skeletal muscle mitochondrial respiration and promote healthy aging in metabolically stressed mammals. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/31462679/Nobiletin_fortifies_mitochondrial_respiration_in_skeletal_muscle_to_promote_healthy_aging_against_metabolic_challenge_ L2 - http://dx.doi.org/10.1038/s41467-019-11926-y DB - PRIME DP - Unbound Medicine ER -