| Sarcopenia is an age-related syndrome characterized by decreased muscle mass and/or decreased muscle strength or physical function decline.This muscle loss is associated with increased risk of adverse health outcomes,including falls,morbidity,loss of independence,disability,and mortality.Since it proposed in 1989,the definition and diagnostic criteria of sarcopenia have made a lot of updates and progress(such as EWGSOP2010,EWGSOP2018,AWGS2014,AWGS2019).However,the current diagnostic criteria for sarcopenia are still not unified,and there is a lack of clinically effective diagnostic biomarkers.Therefore,the current research focus of sarcopenia is to use the pathophysiological mechanism to explore clinically implementable diagnosis and efficacy markers.The skeletal muscle of human,like other mammals,is mainly composed of multinucleated muscle,muscle fibers(or myotubes).As the functional cells of skeletal muscle,muscle fibers contain multiple nuclei,myofilaments,sarcoplasmic reticulum,and a large number of mitochondria.The mitochondrial of muscle fibers are not only the main source of energy for skeletal muscle movement.And several current studies have shown that mitochondria are also a key factor in the occurrence and development of sarcopenia.Hiona A et al.found that there is a large amount of mitochondrial DNA damage(mutations and deletions)in the muscle fibers of people with sarcopenia,which leads to abnormal synthesis of the electron transport chain complex,which not only causes insufficient ATP production,but also leads to excessive ROS production.Make the mitochondrial oxidative metabolism capacity decrease and oxidative stress increase,which in turn promotes the increase of skeletal muscle inflammation,the decrease of muscle protein synthesis,and the increase of hydrolysis,which makes skeletal muscle cell apoptosis and dysfunction and accelerates the development of sarcopenia.Therefore,the change of mitochondrial function is an important window to observe the occurrence and development of sarcopenia,and is a possible biomarker for the diagnosis of sarcopenia.Previous studies have mostly used muscle biopsy to obtain mitochondria in muscle tissues to detect the morphology and energy metabolism of mitochondria.Recent studies have shown that metabolic function testing of circulating cells can replace tissue biopsy to understand the bioenergetics of mitochondria in the body.Circulating cells include red blood cells,granulocytes,white blood cells,and mononuclear cells.Among them,peripheral blood mononuclear cells are rich in mitochondria and have become a common window for mitochondrial function testing and are widely used in cardiovascular diseases,cognitive dysfunction,etc.Research on aging-related diseases,but their relationship with sarcopenia is still very few.Therefore,we innovatively carried out research on the mitochondrial oxidative respiratory function of human peripheral blood mononuclear cells,analyzed its correlation with sarcopenia parameters,and explored possible biomarkers for the diagnosis of sarcopenia in the elderly.The study is divided into two parts:Part I: Muscle strength,muscle mass,physical function and mitochondrial oxidative respiratory function change with agePart II: Study on the correlation between age-related peripheral blood mitochondrial function and sarcopenia parametersPart I: Muscle strength,muscle mass,physical function and peripheral blood mitochondrial oxidative respiratory function change with ageOBJECTIVE: Sarcopenia is characterized by progressive and generalized degenerative loss of skeletal muscle mass,quality,and strength with normal aging.As a result,older adults are at greater risk for falls,bone fracture,disability and mortality.Mitochondria are widely believed to be the vital organelle that generates ATP for skeletal muscle,they are closely related to skeletal muscle strength and muscle mass.The oxidative respiratory function of mitochondria changes during aging,which promotes the occurrence and deterioration of sarcopenia.Due to the current changes in people’s lifestyles and unhealthy eating habits,some foreign studies have found that sarcopenia can occur as early as 30-40 years old,and with the increase of age,it not only endangers individual health,but also brings a huge economic burden to society.Therefore,we first investigated the changes with age of muscle strength,muscle mass,physical function and mitochondrial oxidative respiratory function,reflecting the agerelated changes of sarcopenia.Methods: A total of 65 patients admitted to Jiangsu Province Hospital from June 2019 to August 2020 were enrolled in this study.According to the AWGS2019,grip strength was measured using a hydraulic dynamometer.Measuring the time taken to walk 4 m at a normal pace as the recorded speed,and appendicular skeletal muscle mass(ASM)was estimated by dual-energy X-ray absorptiometry(DXA).Peripheral blood mononuclear cells(PBMCs)were extracted from subjects.Mitochondrial oxidative respiration function was assessed via the Seahorse XF24 analyzer.To evaluate the correlation between the diagnostic parameters of sarcopenia and the mitochondrial oxidative respiratory work and age.RESULTS: Linear correlation analysis showed that grip strength,ASM and age were significantly negatively correlated(P<0.001、0.004),4m gait speed was not correlated with age(P=0.143);and basal respiration,maximal respiration,ATP production and spare respiratory capacity of mitochondria in PBMCs were negatively correlated with age(P<0.001、<0.001、<0.001、<0.001、0.023).After adjustment for gender and BMI,partial correlation analysis showed that grip strength、ASM、4m speed gait were negatively correlated with age(r=-0.537,-0.390,-0.298,P=0.000、0.004、0.029).The mitochondrial oxidative respiratory function in PBMCs,including basal respiration,maximal respiration,ATP production and spare respiratory capacity were also negatively correlated with age(r=-0.558,-0.614,-0.526,-0.582,respectively,P<0.001).CONCLUSION: Muscle strength,ASM,physical function,and mitochondrial oxidative respiratory function all decrease significantly with age.Part II: The correlation of age-related peripheral blood mitochondrial oxidative function and diagnostic parameters of sarcopeniaOBJECTIVE: As we all know,Mitochondria are considered the cellular powerplants of skeletal muscle cells,it generates ATP to meet the energy required of humanskeletal muscle activity.Therefore,mitochondria have been indicated as the core actorsin the occurrence and development of sarcopenia.We detected mitochondrial oxidativerespiratory function of human PBMCs to analyze its correlation with the diagnosticparameters of sarcopenia,that is,the correlation between muscle strength,muscle massand physical function.To explore possible biomarker for the diagnosis of sarcopenia inthe elderly.Methods: A total of 65 patients admitted to Jiangsu Province Hospital from June 2019 to August 2020 were enrolled in this study.According to the AWGS2019,grip strength was measured using a hydraulic dynamometer.Measuring the time taken to walk 4 m at a normal pace as the recorded speed,and appendicular skeletal muscle mass(ASM)was estimated by dual-energy X-ray absorptiometry(DXA).Peripheral blood mononuclear cells(PBMCs)were extracted from subjects.Mitochondrial oxidative respiration function was assessed via the Seahorse XF24 analyzer.Multivariate analysis was conducted by using partial correlation analysis and multiple linear regression,to evaluate the correlation of mitochondrial oxidative respiration function with grip strength,ASM and 4m speed gait.RESULTS: After adjustment for gender and BMI,partial correlation analysis showed that grip strength 、 ASM 、 4m speed gait were positively correlated with mitochondrial oxidative respiratory function in PBMCs,including basal respiration,maximal respiration,ATP production,spare respiratory capacity and proton leak(Grip strength: r=0.414,0.451,0.362,0.420,0.425,P=0.002、0.001、0.008、0.002、0.002;ASM: r=0.319,0.368,0.299,0.352,0.279,P=0.019、0.006、0.028、0.009、0.041).Multiple linear regression analysis showed that grip strength and ASM were positively correlated with basal respiration,maximal respiration,ATP production,spare respiratory capacity and proton leak of mitochondria in PBMCs(grip:β=0.503,0.548,0.452,0.519 and 0.532,t=3.248,3.604,2.774,3.301 and 3.350,P =0.002,0.001,0.008,0.002 and 0.002;ASM:β=0.302,0.355,0.289,0.346 and 0.271,t=2.427,2.856,2.263,2.716 and 2.091,P=0.019,0.006,0.028,0.009 and 0.041).Age was negatively correlated with basal respiration,maximal respiration,ATP production and spare respiratory capacity of mitochondria in PBMCs(β=-0.581,-0.654,-0.558 and-0.640,t=-4.285,-5.157,-3.938 and-4.863,P <0.001).Multiple linear regression model 3 analysis showed that ASM and grip strength had no significant correlation with basal respiration,maximal respiration,ATP production,spare respiratory capacity or proton leak of mitochondria in PBMCs.In addition,the results of multiple linear regression analysis of 4m gait speed and mitochondrial oxidative respiratory function showed no correlation.CONCLUSION: Age-related mitochondrial oxidative respiration in PBMCs can reflect the changes in muscle strength and muscle mass,and combined with grip strength and ASM,may be considered as a biomarker for the evaluation of sarcopenia in the elderly. |
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