Background Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults.
Methods This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay.
Results After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012).
Conclusion These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.
Seong Hee Ahn, Hee-Won Jung, Eunju Lee, Ji Yeon Baek, Il-Young Jang, So Jeong Park, Jin Young Lee, Eunah Choi, Yun Sun Lee, Seongbin Hong, Beom-Jun Kim
Endocrinol Metab. 2022;37(3):487-496. Published online May 27, 2022
Background Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia.
Methods Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay.
Results The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P<0.001 to 0.025).
Conclusion Higher serum sclerostin levels were associated with a lower risk of sarcopenia, low muscle mass, and weak muscle strength in Korean older adults.
Citations
Citations to this article as recorded by
Mechanism and physical activities in bone-skeletal muscle crosstalk Zhonghan Zhao, Kai Yan, Qiao Guan, Qiang Guo, Can Zhao Frontiers in Endocrinology.2024;[Epub] CrossRef
Musculoskeletal disorders and coronary artery disease —promising molecular markers: literature review Viktoria N. Karetnikova, Anastasiya G. Neeshpapa, Evgenia I. Carpova, Olga L. Barbarash CardioSomatics.2024; 15(1): 55. CrossRef
Differences in Type 2 Fiber Composition in the Vastus Lateralis and Gluteus Maximus of Patients with Hip Fractures Jingwen Tian, Minchul Song, Kyu Jeong Cho, Ho Yeop Lee, Sang Hyeon Ju, Jung Ryul Lim, Ha Thi Nga, Thi Linh Nguyen, Ji Sun Moon, Hyo Ju Jang, Jung-Mo Hwang, Hyon-Seung Yi Endocrinology and Metabolism.2024; 39(3): 521. CrossRef
Determinants of bone mass in older adults with normal- and overweight derived from the crosstalk with muscle and adipose tissue Carina O. Walowski, Catrin Herpich, Janna Enderle, Wiebke Braun, Marcus Both, Mario Hasler, Manfred J. Müller, Kristina Norman, Anja Bosy-Westphal Scientific Reports.2023;[Epub] CrossRef
Role of the Osteocyte in Musculoskeletal Disease Anika Shimonty, Lynda F. Bonewald, Fabrizio Pin Current Osteoporosis Reports.2023; 21(3): 303. CrossRef
The role of sclerostin in lipid and glucose metabolism disorders Hewen Jiang, Dijie Li, Ying Han, Nanxi Li, Xiaohui Tao, Jin Liu, Zongkang Zhang, Yuanyuan Yu, Luyao Wang, Sifan Yu, Ning Zhang, Huan Xiao, Xin Yang, Yihao Zhang, Ge Zhang, Bao-Ting Zhang Biochemical Pharmacology.2023; 215: 115694. CrossRef
Cytokines and exosomal miRNAs in skeletal muscle–adipose crosstalk Liu Guo, Menchus Quan, Weijun Pang, Yulong Yin, Fengna Li Trends in Endocrinology & Metabolism.2023; 34(10): 666. CrossRef
Sclerostin: clinical insights in muscle–bone crosstalk Antimo Moretti, Giovanni Iolascon Journal of International Medical Research.2023;[Epub] CrossRef
Anti-sclerostin antibodies: a new frontier in fragility fractures treatment Giovanni Iolascon, Sara Liguori, Marco Paoletta, Giuseppe Toro, Antimo Moretti Therapeutic Advances in Musculoskeletal Disease.2023;[Epub] CrossRef
Sclerostin as a Putative Myokine in Sarcopenia Hyon-Seung Yi Endocrinology and Metabolism.2022; 37(3): 430. CrossRef
Organokines, Sarcopenia, and Metabolic Repercussions: The Vicious Cycle and the Interplay with Exercise Giulia Minniti, Letícia Maria Pescinini-Salzedas, Guilherme Almeida dos Santos Minniti, Lucas Fornari Laurindo, Sandra Maria Barbalho, Renata Vargas Sinatora, Lance Alan Sloan, Rafael Santos de Argollo Haber, Adriano Cressoni Araújo, Karina Quesada, Jesse International Journal of Molecular Sciences.2022; 23(21): 13452. CrossRef
Background Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it.
Methods Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research.
Results Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone.
Conclusion These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.
Citations
Citations to this article as recorded by
Molecular mechanisms underlying sarcopenia in heart failure Cody A. Rutledge The Journal of Cardiovascular Aging.2024;[Epub] CrossRef
Role of glucocorticoid and mineralocorticoid receptors in rainbow trout (Oncorhynchus mykiss) skeletal muscle: A transcriptomic perspective of cortisol action Jorge E. Aedo, Rodrigo Zuloaga, Daniela Aravena-Canales, Alfredo Molina, Juan Antonio Valdés Frontiers in Physiology.2023;[Epub] CrossRef
Effect of 11-Deoxycorticosterone in the Transcriptomic Response to Stress in Rainbow Trout Skeletal Muscle Rodrigo Zuloaga, Daniela Aravena-Canales, Jorge Eduardo Aedo, Cesar Osorio-Fuentealba, Alfredo Molina, Juan Antonio Valdés Genes.2023; 14(2): 512. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung Endocrinology and Metabolism.2023; 38(6): 597. CrossRef
Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults Sunghwan Ji, Kyunggon Kim, So Jeong Park, Jin Young Lee, Hee-Won Jung, Hyun Ju Yoo, Il-Young Jang, Eunju Lee, Ji Yeon Baek, Beom-Jun Kim Endocrinology and Metabolism.2023; 38(6): 701. CrossRef
The Role of Aldosterone in OSA and OSA-Related Hypertension Yi Wang, Chuan Xiang Li, Ying Ni Lin, Li Yue Zhang, Shi Qi Li, Liu Zhang, Ya Ru Yan, Fang Ying Lu, Ning Li, Qing Yun Li Frontiers in Endocrinology.2022;[Epub] CrossRef
Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease Daiji Kawanami, Yuichi Takashi, Yoshimi Muta, Naoki Oda, Dai Nagata, Hiroyuki Takahashi, Makito Tanabe Frontiers in Pharmacology.2021;[Epub] CrossRef
Background The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults.
Methods Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline.
Results Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index.
Conclusion Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.
Citations
Citations to this article as recorded by
Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization Mingchong Liu, Xiao Fu, Daqian Yu, Meng Li, Yutao Pan, Chensong Yang, Guixin Sun Journal of Cachexia, Sarcopenia and Muscle.2024; 15(3): 1121. CrossRef
Age-associated functional healing of musculoskeletal trauma through regenerative engineering and rehabilitation Krista M. Habing, Cynthia A. Alcazar, Victoria R. Duke, Yong How Tan, Nick J. Willett, Karina H. Nakayama Biomaterials Science.2024;[Epub] CrossRef
C-C motif chemokine CCL11 is a novel regulator and a potential therapeutic target in non-alcoholic fatty liver disease Zhiwen Fan, Xinyue Sun, Xuelian Chen, Huimin Liu, Xiulian Miao, Yan Guo, Yong Xu, Jie Li, Xiaoping Zou, Zilong Li JHEP Reports.2023; : 100754. CrossRef
C–C motif chemokine CCL11 is a novel regulator and a potential therapeutic target in non-alcoholic fatty liver disease Zhiwen Fan, Xinyue Sun, Xuelian Chen, Huimin Liu, Xiulian Miao, Yan Guo, Yong Xu, Jie Li, Xiaoping Zou, Zilong Li JHEP Reports.2023; 5(9): 100805. CrossRef
Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity Jin-Young Lee, Da-Ae Kim, Eun-Young Kim, Eun-Ju Chang, So-Jeong Park, Beom-Jun Kim International Journal of Molecular Sciences.2021; 22(9): 4717. CrossRef
Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor Jin Young Lee, Da Ae Kim, Eunah Choi, Yun Sun Lee, So Jeong Park, Beom-Jun Kim Endocrinology and Metabolism.2021; 36(4): 865. CrossRef