한빛사논문
- 조회537
Ju-Hyeon Bae 1 2 †, Areum Jo 3 †, Sung Chun Cho 4 †, Yun-Il Lee 4 5 †, Tae-In Kam 6 7 †, Chang-Lim You 1 2, Hyeon-Ju Jeong 1 2, Hyebeen Kim 1 2, Myong-Ho Jeong 1 2, Yideul Jeong 8, Young Wan Ha 9, Yu Seon Kim 4, Jiwoon Kim 4 10, Seung-Hwa Woo 4 10, Minseok S Kim 10, Eui Seok Shin 9, Sang Ok Song 11, Hojin Kang 2 3, Rin Khang 2 3, Soojeong Park 2 3, Joobae Park 1, Valina L. Dawson 6 7 12 13 14 15 16, Ted M. Dawson 5 7 13 14 15 16 *, Sang Chul Park 4 17 *, Joo-Ho Shin 2 3 18 *, Jong-Sun Kang 1 2 8 18 *
1Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
2Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
3Department of Pharmacology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
4Well Aging Research Center, Division of Biotechnology, DGIST, Daegu 42988, South Korea.
5Department of Interdisciplinary Studies, DGIST, Daegu 42988, South Korea.
6Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
7Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
8Research Institute of Aging-related Diseases, AniMusCure Inc., Suwon 440-746, South Korea.
9Well Aging Research Center, Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd., Suwon, Gyeonggi-do 446-712, South Korea.
10Department of New Biology, DGIST, Daegu 42988, South Korea.
11Standigm Inc., Seoul 06250, South Korea.
12Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
13Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
14Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
15Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA.
16Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685, USA.
17Future Life & Society Research Center, Chonnam National University, Gwangju 61469, South Korea.
18Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 06351, South Korea.
†These authors contributed equally to this work.
*Corresponding author: correspondence to Ted M Dawson, Sang Chul Park, Joo-Ho Shin or Jong-Sun Kang
Abstract
Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis. Reduced PGC-1α abundance is linked to skeletal muscle weakness in aging or pathological conditions, such as neurodegenerative diseases and diabetes; thus, elevating PGC-1α abundance might be a promising strategy to treat muscle aging. Here, we performed high-throughput screening and identified a natural compound, farnesol, as a potent inducer of PGC-1α. Farnesol administration enhanced oxidative muscle capacity and muscle strength, leading to metabolic rejuvenation in aged mice. Moreover, farnesol treatment accelerated the recovery of muscle injury associated with enhanced muscle stem cell function. The protein expression of Parkin-interacting substrate (PARIS/Zfp746), a transcriptional repressor of PGC-1α, was elevated in aged muscles, likely contributing to PGC-1α reduction. The beneficial effect of farnesol on aged muscle was mediated through enhanced PARIS farnesylation, thereby relieving PARIS-mediated PGC-1α suppression. Furthermore, short-term exercise increased PARIS farnesylation in the muscles of young and aged mice, whereas long-term exercise decreased PARIS expression in the muscles of aged mice, leading to the elevation of PGC-1α. Collectively, the current study demonstrated that the PARIS-PGC-1α pathway is linked to muscle aging and that farnesol treatment can restore muscle functionality in aged mice through increased farnesylation of PARIS.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-09-08)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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