Exercise-induced signaling activation by Chrysanthemum zawadskii and its active compound, linarin, ameliorates age-related sarcopenia through Sestrin 1 regulation

Farida S Nirmala; Hyunjung Lee; Young-In Kim; Jeong-Hoon Hahm; Hyo-Deok Seo; Minjung Kim; Chang Hwa Jung; Jiyun Ahn

doi:10.1016/j.phymed.2024.155695

Exercise-induced signaling activation by Chrysanthemum zawadskii and its active compound, linarin, ameliorates age-related sarcopenia through Sestrin 1 regulation

Phytomedicine. 2024 Apr 30:129:155695. doi: 10.1016/j.phymed.2024.155695. Online ahead of print.

Authors

Farida S Nirmala¹, Hyunjung Lee², Young-In Kim², Jeong-Hoon Hahm², Hyo-Deok Seo², Minjung Kim³, Chang Hwa Jung¹, Jiyun Ahn⁴

Affiliations

¹ Department of Food Biotechnology, University of Science and Technology, Daejeon, South Korea; Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea.
² Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea.
³ Research Group of Personalized Diet, Korea Food Research Institute, Wanju-gun, South Korea.
⁴ Department of Food Biotechnology, University of Science and Technology, Daejeon, South Korea; Research Group of Aging and Metabolism, Korea Food Research Institute, Wanju-gun, South Korea. Electronic address: jyan@kfri.re.kr.

PMID: 38728922
DOI: 10.1016/j.phymed.2024.155695

Abstract

Background: Exercise is an effective strategy to prevent sarcopenia, but high physical inactivity in the elderly requires alternative therapeutic approaches. Exercise mimetics are therapeutic compounds that simulate the beneficial effects of exercise on skeletal muscles. However, the toxicity and adverse effects of exercise mimetics raise serious concerns.

Purpose: We aimed to search novel plant-based alternatives to activate exercise induced-signaling.

Methods: We used open databases and luciferase assays to identify plant-derived alternatives to activate exercise-induced signaling and compared its efficacy to mild intensity continuous training (MICT) in aged C57BL/6 mice. The nineteen-month-old mice were either fed an experimental diet supplemented with the isolated alternative or subjected to MICT for up to 21 mo of age.

Results: Our analysis revealed that Chrysanthemum zawadskii Herbich var latillobum (Maxim.) Kitamura (CZH), a medicinal plant rich in linarin, is a novel activator of peroxisome proliferator-activated receptor δ (PPARδ) and estrogen-related receptor γ (ERRγ), key regulators of exercise-induced positive effects on muscles. CZH supplementation ameliorated the loss of muscle function and mass, and increased PPARδ and ERRγ expression in mouse muscles. CZH also improved mitochondrial functions and proteostasis in aged mice, similar to MICT. Furthermore, CZH and linarin induced the activation of Sestrin 1, a key mediator of exercise benefits, in muscle. Silencing Sestrin 1 negated the increase in myogenesis and mitochondrial respiration by CZH and linarin in primary myoblasts from old mice.

Conclusion: Our findings suggest the potential of CZH as a novel plant-derived alternative to activate exercise-induced signaling for preventing sarcopenia in sedentary older adults. This could offer a safer therapeutic option for sarcopenia treatment.

Keywords: Aging; Exercise; Mitochondria; Muscle atrophy; Sarcopenia.