Study of Muscle, Mobility and Aging (SOMMA)
肌肉、活动能力和衰老研究 (SOMMA)
基本信息
- 批准号:10652212
- 负责人:
- 金额:$ 24.55万
- 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:2018-06-15 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:Adipose tissueAdministrative SupplementAgeAgingAncillary StudyAutophagocytosisAwardBioenergeticsBiologicalBiopsyBloodCOVID-19 pandemicClinicalCohort StudiesCommunitiesComplexContractile ProteinsCreatineDataData SetDenervationDependenceDevelopmentElderlyEnrollmentEnsureFresh TissueFundingGait speedGene ClusterGene ExpressionGene Expression ProfileGenetic TranscriptionGoalsHealth Care CostsHuman ResourcesImageImpairmentIndividualInterruptionInterventionJusticeK-Series Research Career ProgramsKnee OsteoarthritisLaboratoriesLaboratory StudyLongitudinal StudiesMagnetic Resonance ImagingMeasuresMethodsMitochondriaMuscleMuscular AtrophyNeighborhoodsOutcomeParticipantPathway interactionsPeripheralPeripheral Blood Mononuclear CellPersonsPhysical activityPlayPrincipal InvestigatorPropertyQuality ControlQuality of lifeRecordsResearch PersonnelResolutionRiskRoleScienceSkeletal MuscleStatistical Data InterpretationSymptomsTechnologyTestingTimeTissue BanksTissuesUpdateWalkingWomanX-Ray Computed Tomographyage relatedagedbasebuilt environmentclinical phenotypecohortcostdisabilityexercise regimenfecal microbiomefitnessfollow-upforestindividual variationinnovationinterestmenmetermuscle agingmuscle formnew therapeutic targetnoveloxidative damageparticipant enrollmentpreventprimary outcomeprospectivequadriceps musclerecruitreduced muscle masstissue archivetissue processingtranscriptometranscriptome sequencingtranscriptomicsurinarywalking speed
项目摘要
Mobility inevitably declines with age, more in some than other people, often leading to mobility disability
with dependency, decreased quality of life, and enormous health care costs. The role of age-related biological
changes in skeletal muscle on the decline in mobility is poorly understood. We hypothesize that muscle mass
and the capacity to produce ATP are strong determinants of the mobility disability in older adults. Based on
advances from laboratory studies of muscle aging, we also hypothesize that denervation, oxidative damage,
and decreased autophagic flux interact and contribute to declines in fitness, endurance and an increased risk
of mobility disability. We will also use transcriptomic profiling by RNAseq to discover patterns of gene
expression that play important roles in the loss of mobility with aging.
In the Study of Muscle Mobility and Aging (SOMMA), a prospective, longitudinal study of men and
women age 70 to 90, our team of experts in clinical and laboratory sciences will use innovative and state-of-
the-art technologies with rigorous quality control to test these hypotheses and discover new pathways for the
loss of mobility with aging. We will measure quadriceps contractile volume by MRI and total muscle mass by
d3 creatine dilution. We will use 31PMRS to assess the capacity of the quadriceps to generate ATP (ATPmax).
In tissue form, muscle biopsies quantify denervation and oxidative damage to contractile proteins. SOMMA will
be the first to quantify autophagic flux to assess the role of autophagy in the loss of mobility with aging. We use
respirometry on fresh tissue to quantify the contribution of mitochondria to ATPmax and mobility disability.
These properties interact: for example, decreased autophagic flux promotes the accumulation of oxidative
damage and denervation, and understanding these relationships will guide the analysis and interpretation of
our results. Furthermore, we will use unbiased RNA-sequencing (RNA-seq) to profile the entire transcriptome
to discover new associations between clusters of genes and individual variation in rates of loss of fitness (peak
VO2), muscle mass, and risk of mobility disability.
Field centers at Wake Forest and Pittsburgh, with exceptional track records for recruiting and retaining
older adults in complex studies, will enroll 875 women and men age 70–89 with a gait speed ≤ 1.0 m/s,
providing sufficient power to identify important relationships between individual and combinations of properties
and the risk of mobility disability.
SOMMA may identify and prioritize targets for new therapeutics and tailored exercise regimens. We
also will create a unique archive of tissue, blood, with longitudinal data about important clinical outcomes that
the scientific community can use to efficiently test new hypotheses about muscle and loss of mobility with
aging.
随着年龄的增长,行动能力不可避免地下降,某些人比其他人更严重,常常导致行动障碍
依赖、生活质量下降以及与年龄相关的生物学的巨大医疗费用。
我们对骨骼肌变化对活动能力下降的影响知之甚少。
和产生 ATP 的能力是老年人行动障碍的重要决定因素。
随着肌肉老化实验室研究的进展,我们还研究了去神经作用、氧化损伤、
和自噬流减少相互作用,导致健康、耐力下降和风险增加
我们还将使用 RNAseq 进行转录组分析来发现基因模式。
表达在随着衰老而丧失活动能力方面发挥重要作用。
在肌肉活动性和衰老研究 (SOMMA) 中,一项针对男性和女性的前瞻性纵向研究
针对 70 至 90 岁的女性,我们的临床和实验室科学专家团队将使用创新和最先进的技术
最先进的技术和严格的质量控制来测试这些假设并发现新的途径
我们将通过 MRI 测量股四头肌收缩量,并通过以下方法测量总肌肉质量。
d3 肌酸稀释液我们将使用 31PMRS 来评估股四头肌产生 ATP (ATPmax) 的能力。
在组织形式中,肌肉活检可量化 SOMMA 的去神经支配和氧化损伤。
成为第一个量化自噬通量以评估自噬在衰老过程中活动能力丧失中的作用的人。
对新鲜组织进行呼吸测量,以量化线粒体对 ATPmax 和活动障碍的贡献。
这些特性相互作用:例如,自噬通量减少会促进氧化物质的积累
损伤和去神经支配,理解这些关系将指导分析和解释
此外,我们将使用无偏 RNA 测序 (RNA-seq) 来分析整个转录组。
发现基因簇与体能丧失率个体差异之间的新关联(峰值
VO2)、肌肉质量和行动障碍的风险。
位于维克森林和匹兹堡的实地中心,在招募和保留方面拥有出色的记录
复杂研究中的老年人将招募 875 名 70-89 岁的女性和男性,步态速度 ≤ 1.0 m/s,
提供足够的能力来识别个体和属性组合之间的重要关系
以及行动不便的风险。
SOMMA 可以确定新疗法和定制锻炼方案的目标并确定优先顺序。
还将创建一个独特的组织、血液档案,其中包含重要临床结果的纵向数据,
科学界可以用来有效地测试关于肌肉和活动能力丧失的新假设
老化。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the Study of Muscle, Mobility and Aging (SOMMA).
在肌肉、活动性和衰老研究 (SOMMA) 中,老年人骨骼肌中的自噬基因表达与身体表现、肌肉体积和线粒体功能相关。
- DOI:10.1101/2023.11.04.23297979
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Coen,PaulM;Huo,Zhiguang;Tranah,GregoryJ;Barnes,HaleyN;Cawthon,PeggyM;Hepple,RussellT;Toledo,FredericoGS;Evans,DanielS;Fernández,OlayaSantiago;Cuervo,AnaMaria;Kritchevsky,StevenB;Newman,AnneB;Cummings,StevenR;Esser,K
- 通讯作者:Esser,K
The cellular bases of mobility from the Study of Muscle, Mobility and Aging (SOMMA).
来自肌肉、活动性和衰老研究 (SOMMA) 的活动性细胞基础。
- DOI:10.1111/acel.14129
- 发表时间:2024
- 期刊:
- 影响因子:7.8
- 作者:Cummings,StevenR;Coen,PaulM;Ferrucci,Luigi
- 通讯作者:Ferrucci,Luigi
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STEVEN RON CUMMINGS其他文献
STEVEN RON CUMMINGS的其他文献
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{{ truncateString('STEVEN RON CUMMINGS', 18)}}的其他基金
Study of Muscle, Mobility and Aging (SOMMA)
肌肉、活动能力和衰老研究 (SOMMA)
- 批准号:
10170192 - 财政年份:2018
- 资助金额:
$ 24.55万 - 项目类别:
Prevention of Fractures in Patients with Parkinson's Disease
帕金森病患者骨折的预防
- 批准号:
10617169 - 财政年份:2018
- 资助金额:
$ 24.55万 - 项目类别:
Study of Muscle, Mobility and Aging: SOMMA2
肌肉、活动能力和衰老研究:SOMMA2
- 批准号:
10913728 - 财政年份:2018
- 资助金额:
$ 24.55万 - 项目类别:
Study of Muscle, Mobility and Aging (SOMMA)
肌肉、活动能力和衰老研究 (SOMMA)
- 批准号:
10441623 - 财政年份:2018
- 资助金额:
$ 24.55万 - 项目类别:
Study of Muscle, Mobility and Aging (SOMMA)
肌肉、活动能力和衰老研究 (SOMMA)
- 批准号:
10015194 - 财政年份:2018
- 资助金额:
$ 24.55万 - 项目类别:
Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins
衰老相关临床结果和Gero蛋白的综合评价
- 批准号:
9519838 - 财政年份:2016
- 资助金额:
$ 24.55万 - 项目类别:
Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins
衰老相关临床结果和Gero蛋白的综合评价
- 批准号:
9279037 - 财政年份:2016
- 资助金额:
$ 24.55万 - 项目类别:
Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins - SUPPLEMENT
衰老相关临床结果和老年蛋白的综合评估 - 补充材料
- 批准号:
9445352 - 财政年份:2016
- 资助金额:
$ 24.55万 - 项目类别:
Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins
衰老相关临床结果和Gero蛋白的综合评价
- 批准号:
9119555 - 财政年份:2016
- 资助金额:
$ 24.55万 - 项目类别:
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