{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:31:06Z","timestamp":1790857866261,"version":"4.1.0"},"reference-count":56,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"711","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,8,30]]},"abstract":"<jats:p>\n                    Peroxisome proliferator\u2013activated receptor-\u03b3 coactivator-1\u03b1 (PGC-1\u03b1) is a master regulator of mitochondrial biogenesis. Reduced PGC-1\u03b1 abundance is linked to skeletal muscle weakness in aging or pathological conditions, such as neurodegenerative diseases and diabetes; thus, elevating PGC-1\u03b1 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-1\u03b1. 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\/\n                    <jats:italic>Zfp746<\/jats:italic>\n                    ), a transcriptional repressor of PGC-1\u03b1, was elevated in aged muscles, likely contributing to PGC-1\u03b1 reduction. The beneficial effect of farnesol on aged muscle was mediated through enhanced PARIS farnesylation, thereby relieving PARIS-mediated PGC-1\u03b1 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-1\u03b1. Collectively, the current study demonstrated that the PARIS\u2013PGC-1\u03b1 pathway is linked to muscle aging and that farnesol treatment can restore muscle functionality in aged mice through increased farnesylation of PARIS.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abh3489","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T13:59:22Z","timestamp":1693403962000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":24,"title":["Farnesol prevents aging-related muscle weakness in mice through enhanced farnesylation of Parkin-interacting substrate"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-6820","authenticated-orcid":true,"given":"Ju-Hyeon","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."},{"name":"Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5187-0407","authenticated-orcid":true,"given":"Areum","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8678-2370","authenticated-orcid":true,"given":"Sung Chun","family":"Cho","sequence":"additional","affiliation":[{"name":"Well Aging Research Center, Division of Biotechnology, DGIST, Daegu 42988, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9203-2234","authenticated-orcid":true,"given":"Yun-Il","family":"Lee","sequence":"additional","affiliation":[{"name":"Well Aging Research Center, Division of Biotechnology, DGIST, Daegu 42988, South Korea."},{"name":"Department of Interdisciplinary Studies, DGIST, Daegu 42988, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7241-4902","authenticated-orcid":true,"given":"Tae-In","family":"Kam","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3224-7952","authenticated-orcid":true,"given":"Chang-Lim","family":"You","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."},{"name":"Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-2559","authenticated-orcid":true,"given":"Hyeon-Ju","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."},{"name":"Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3066-7098","authenticated-orcid":true,"given":"Hyebeen","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."},{"name":"Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-9869","authenticated-orcid":true,"given":"Myong-Ho","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."},{"name":"Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2667-9256","authenticated-orcid":true,"given":"Yideul","family":"Jeong","sequence":"additional","affiliation":[{"name":"Research Institute of Aging-related Diseases, AniMusCure Inc., Suwon 440-746, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2950-2000","authenticated-orcid":true,"given":"Young Wan","family":"Ha","sequence":"additional","affiliation":[{"name":"Well Aging Research Center, Samsung Advanced Institute of Technology, Samsung Electronics Co. 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