Role of the Extracellular Matrix in Age-Associated Strength Loss: Combining Imaging and Biochemistry to create a Multi-Scale Mesh-free Model
细胞外基质在与年龄相关的力量损失中的作用:结合成像和生物化学创建多尺度无网格模型
基本信息
- 批准号:10398870
- 负责人:
- 金额:$ 54.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdipose tissueAdultAffectAgeAged, 80 and overAgingAmericanAnimalsArchitectureAreaBiochemicalBiochemistryBiological MarkersBiologyBiopsy SpecimenClinicalComputer ModelsConnective TissueContractile ProteinsCross-Sectional StudiesDataDevelopmentDiffusionDiffusion Magnetic Resonance ImagingDiseaseElderlyElectromyographyEquilibriumExtracellular MatrixFatty acid glycerol estersFiberFrail ElderlyFutureGoalsGrantHealthcare SystemsHumanHydroxyprolineImageImmunochemistryImmunohistochemistryImmunoprecipitationImpairmentIndependent LivingLateralLife ExpectancyLinkLongevityMagnetic Resonance ImagingMapsMeasuresMetabolismMethodsModelingModificationMorphologyMusMuscleMuscle ContractionMuscle FibersMuscle WeaknessMuscle functionMuscular AtrophyMusculoskeletalNervePatientsPatternPersonsPhasePopulationPost-Translational Protein ProcessingProcessPropertyProteinsRehabilitation therapyRodentRoleRyanodine Receptor Calcium Release ChannelSirius Red F3BStatistical ModelsSurfaceTestingTimeWaterWorkage relatedaging populationbasebioimagingclinical applicationcohortcrosslinkexhaustionfrailtygel electrophoresisin vivoindexingmulti-scale modelingmuscle formmuscle strengthmuscular structurenovelpreventrehabilitation paradigmrelating to nervous systemsarcopeniaskeletal muscle wastingtooltransmission processyoung adult
项目摘要
The overall goal of these studies is to elucidate the roles of different musculoskeletal factors in the loss
of muscle quality with aging, with specific focus on the extracellular matrix (ECM). Sarcopenia, defined as age-
associated loss of skeletal muscle mass, currently affects 50 million in the US with the number expected to rise
to 200 million by 2050. The concomitant, disproportionately larger loss of muscle strength compared to size,
termed dynopenia, cannot be accounted for completely by the widely believed primary causes, of neural and
muscle contractility origin. Recent evidence from animal studies suggest that the ECM may be an important
cause of loss of muscle quality since the more than 80% of force transmission occurring laterally through the
ECM in young mice is significantly reduced in aging animals. The ECM remodels considerably with aging, in
content, regional distribution, collagenous composition and cross-linking. However, the contribution of changes
in the ECM to the loss of muscle quality in humans has never been investigated comprehensively. We hy-
pothesize that altered lateral force transmission due to ECM remodeling contributes to dynopenia.
A highly integrated array of MR imaging, neural activation, and biochemical and immuno-histochemical
analysis on muscle biopsy samples, will be used to characterize the human plantar and dorsiflexor muscles in
a cross-sectional study (N=30 each) of: (i) young (21-30 years) adults, (ii) active seniors (> 75 years) with min-
imal dynopenia, and (iii) frail seniors (> 75 years) with significant dynopenia. To test the Hypothesis that dy-
nopenia cannot be totally accounted for by decreases in muscle contractile quality, mass and neural drive,
Specific Aim (SA)-1 will estimate the contributions of muscle and nerve to dynopenia by assessing age and
frailty induced changes in (1) muscle mass, architecture using diffusion tensor MRI, material properties from
dynamic MRI; (2) contractile quality based on ryanodine receptor modification, (3) fiber size using immu-
nochemistry, and (4) muscle activation. To test the Hypothesis that ECM remodeling will account for the dis-
crepancy identified in the SA-1, the contribution of ECM remodeling will be determined in SA-2 via quantifica-
tion of (1) indices related to lateral transmission of force (shear strain, angle between the axis of shortening
and muscle fiber from dynamic MRI), and (2) the content, orientation and composition of the ECM determined
from MRI and cellular analysis. SA-3 will develop and validate a mesh-free multiscale (multi-cellular, compo-
nent, and structural level) computational model, to establish mechanistic and causal links between subject-
specific data from SA-1 and SA-2 to dynopenia with a focus on changes in lateral transmission of force.
Such exhaustive characterization that targets all the major determinants of age-related force loss will
enable us to (i) elucidate the role of ECM remodeling in dynopenia, (ii) identify surrogate imaging bio-markers
for potential clinical applications, and (iii) assess the predictive power of the computational model to potentially
inform the translational development of subject/ cohort-specific rehabilitative paradigms for a future RO1 grant.
这些研究的总体目标是阐明不同的肌肉骨骼因素在损失中的作用
项目成果
期刊论文数量(25)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Myofibrillar protein synthesis rates are increased in chronically exercised skeletal muscle despite decreased anabolic signaling.
- DOI:10.1038/s41598-022-11621-x
- 发表时间:2022-05-09
- 期刊:
- 影响因子:4.6
- 作者:
- 通讯作者:
Magnetic resonance imaging based muscle strain rate mapping during eccentric contraction to study effects of unloading induced by unilateral limb suspension.
基于磁共振成像的偏心收缩期间的肌肉应变率图,以研究单侧肢体悬挂引起的卸载效果。
- DOI:10.4081/ejtm.2019.8935
- 发表时间:2020
- 期刊:
- 影响因子:2.2
- 作者:Sinha,Usha;Malis,Vadim;Csapo,Robert;Narici,Marco;Sinha,Shantanu
- 通讯作者:Sinha,Shantanu
Investigating the Correlation between Force Output, Strains, and Pressure for Active Skeletal Muscle Contractions.
研究主动骨骼肌收缩的力输出、应变和压力之间的相关性。
- DOI:
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Taneja,Karan;He,Xiaolong;Hodgson,John;Sinha,Usha;Sinha,Shantanu;Chen,JS
- 通讯作者:Chen,JS
A Feature-Encoded Physics-Informed Parameter Identification Neural Network for Musculoskeletal Systems.
- DOI:10.1115/1.4055238
- 发表时间:2022-12-01
- 期刊:
- 影响因子:1.7
- 作者:Taneja, Karan;He, Xiaolong;He, QiZhi;Zhao, Xinlun;Lin, Yun-An;Loh, Kenneth J.;Chen, Jiun-Shyan
- 通讯作者:Chen, Jiun-Shyan
Microstructural analysis of skeletal muscle force generation during aging.
- DOI:10.1002/cnm.3295
- 发表时间:2020-01
- 期刊:
- 影响因子:2.1
- 作者:Zhang Y;Chen JS;He Q;He X;Basava RR;Hodgson J;Sinha U;Sinha S
- 通讯作者:Sinha S
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{{ truncateString('Shantanu Sinha', 18)}}的其他基金
Role of the Extracellular Matrix in Age-Associated Strength Loss: Combining Imaging and Biochemistry to create a Multi-Scale Mesh-free Model
细胞外基质在与年龄相关的力量损失中的作用:结合成像和生物化学创建多尺度无网格模型
- 批准号:
9920653 - 财政年份:2018
- 资助金额:
$ 54.94万 - 项目类别:
Role of the Extracellular Matrix in Age-Associated Strength Loss: Combining Imaging and Biochemistry to create a Multi-Scale Mesh-free Model
细胞外基质在与年龄相关的力量损失中的作用:结合成像和生物化学创建多尺度无网格模型
- 批准号:
9751138 - 财政年份:2018
- 资助金额:
$ 54.94万 - 项目类别:
In Vivo Imaging-Based Multiscale Modeling of Normal and Atrophied Human Lower Leg
基于体内成像的正常和萎缩人类小腿的多尺度建模
- 批准号:
8513915 - 财政年份:2006
- 资助金额:
$ 54.94万 - 项目类别:
In Vivo Imaging-Based Multiscale Modeling of Normal and Atrophied Human Lower Leg
基于体内成像的正常和萎缩人类小腿的多尺度建模
- 批准号:
8296008 - 财政年份:2006
- 资助金额:
$ 54.94万 - 项目类别:
In-vivo MR Tractography and FEM Study of Human Lower Leg
人体小腿的体内 MR 纤维束成像和 FEM 研究
- 批准号:
7026189 - 财政年份:2006
- 资助金额:
$ 54.94万 - 项目类别:
In-vivo MR Tractography and FEM Study of Human Lower Leg
人体小腿的体内 MR 纤维束成像和 FEM 研究
- 批准号:
7458022 - 财政年份:2006
- 资助金额:
$ 54.94万 - 项目类别:
In-vivo MR Tractography and FEM Study of Human Lower Leg
人体小腿的体内 MR 纤维束成像和 FEM 研究
- 批准号:
7260544 - 财政年份:2006
- 资助金额:
$ 54.94万 - 项目类别:
In Vivo Imaging-Based Multiscale Modeling of Normal and Atrophied Human Lower Leg
基于体内成像的正常和萎缩人类小腿的多尺度建模
- 批准号:
8188321 - 财政年份:2006
- 资助金额:
$ 54.94万 - 项目类别:
In Vivo Imaging-Based Multiscale Modeling of Normal and Atrophied Human Lower Leg
基于体内成像的正常和萎缩人类小腿的多尺度建模
- 批准号:
8693925 - 财政年份:2006
- 资助金额:
$ 54.94万 - 项目类别:
In-vivo MR Tractography and FEM Study of Human Lower Leg
人体小腿的体内 MR 纤维束成像和 FEM 研究
- 批准号:
7638559 - 财政年份:2006
- 资助金额:
$ 54.94万 - 项目类别:
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