Investigating the role of adipose tissue in mobility and aging (SOMMA-AT)
研究脂肪组织在活动能力和衰老中的作用 (SOMMA-AT)
基本信息
- 批准号:10263254
- 负责人:
- 金额:$ 80.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-15 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdipose tissueAffectAgingAncillary StudyArchivesAtrophicBiologicalBiopsyBloodBlood CirculationBlood specimenCD4 Positive T LymphocytesCDKN2A geneCaliberCell AgingCellsCessation of lifeCollaborationsContractile ProteinsDataDenervationDental crownsElderlyEnzyme-Linked Immunosorbent AssayEtiologyFelis catusFundingFutureGenerationsGlycerolGoalsHumanHydrogen PeroxideImmunoassayIn VitroInflammationInsulinInsulin ResistanceIsoproterenolKnowledgeLinkLongevityLongitudinal StudiesMetabolicMissionMitochondriaMorbidity - disease rateMuscleMuscle CellsMuscle FibersMuscle functionNecrosisOutcomeOxidative StressParentsPhysiological ProcessesPopulationPrevention strategyProcessProductionPropertyProteinsProteomicsPublishingQuality of lifeReportingResearch PersonnelResourcesRespirationRoleSkeletal MuscleStructureTweensUnited States National Institutes of HealthVO2maxWalkingWorkaging populationbasebiobankdisabilityexperimental studyfitnessflexibilityfunctional outcomesglycemic controlimprovedin vivoinsulin sensitivitylipid biosynthesismanmortalitymouse modelmuscle formnoveloxidative damagepreservationpreventprotein expressionself-renewalsenescenceskeletal muscle wastingstem cell proliferationtargeted treatmenttranslational impacttrial designwalking speed
项目摘要
Project Summary/Abstract
Targeted therapies for aging-related mobility disability are urgently needed to preserve quality of life and pre-
vent morbidity/mortality in the rapidly expanding aging population. Progressive decline in mobility with aging
has been partially attributed to loss of skeletal muscle (SM) mass and function, as well as an increase in the
quantity of adipose tissue (AT). The quality of AT and AT-secreted factors are also likely to influence this pro-
cess, yet meager evidence exists for this notion. Cellular senescence, a phenomenon by which normal healthy
cells cease to divide and therefore become programmed for cellular death, occurs in adipose tissue and is as-
sociated with poorer mobility. Furthermore, secreted factors from AT, potentially from senescent or dying cells,
induces insulin resistance and atrophy in human skeletal muscle cells. Collectively, these data demonstrate
that AT quality (i.e., structure and function) can directly impact skeletal muscle function. This adipose-skeletal
muscle crosstalk has been increasingly implicated in poor functional and metabolic outcomes in younger hu-
man populations. The unique contributions of AT structure and function and AT-secreted factors to mobility de-
cline and skeletal muscle function in the context of human aging have not been addressed. The proposed stud-
ies will fill a critical knowledge gap by directly assessing structural and functional components of AT in aging
and using their associations with mobility to identify AT-secreted proteins that negatively impact skeletal mus-
cle function. The long-term goal of this ancillary study is to leverage and add to the outstanding resources of
the parent SOMMA project to understand the contribution of AT quality, AT-secreted factors and AT-skeletal
muscle crosstalk to mobility disability and other complications of aging in humans. Our overall objective is to
identify key structural and functional components of AT quality - including necrosis, senescence, inflammation,
self-renewal and metabolic flexibility - and AT-secreted proteins that influence mobility via direct effects on
skeletal muscle. We hypothesize that AT structure and function influences AT-secreted proteins that contribute
to aging-related mobility outcomes by directly impacting skeletal muscle function. The stated purpose of Aim 1
is to determine which structural and functional components of AT are associated with slower walking speed.
We posit that increased cellular senescence, increased necrosis, increased inflammation, decreased capacity
for self-renewal and metabolic inflexibility will be associated with slower walking speed. For Aim 2, we antici-
pate that incubation of human muscle cells with known and novel secreted proteins - identified through stand-
ard immunoassay panels and unbiased proteomics and shown to be associated with aberrations in AT struc-
ture and/or function - will worsen mitochondrial respiration, increase oxidative stress, decrease contractility and
muscle cell diameter. This work will have a positive translational impact by improving strategies for prevention
and/or treatment of aging-related mobility disability and by promoting knowledge and facilitating future studies
to understanding AT-skeletal muscle crosstalk across the lifespan.
Project Summary/Abstract
Targeted therapies for aging-related mobility disability are urgently needed to preserve quality of life and pre-
vent morbidity/mortality in the rapidly expanding aging population. Progressive decline in mobility with aging
has been partially attributed to loss of skeletal muscle (SM) mass and function, as well as an increase in the
quantity of adipose tissue (AT). The quality of AT and AT-secreted factors are also likely to influence this pro-
cess, yet meager evidence exists for this notion. Cellular senescence, a phenomenon by which normal healthy
cells cease to divide and therefore become programmed for cellular death, occurs in adipose tissue and is as-
sociated with poorer mobility. Furthermore, secreted factors from AT, potentially from senescent or dying cells,
induces insulin resistance and atrophy in human skeletal muscle cells. Collectively, these data demonstrate
that AT quality (i.e., structure and function) can directly impact skeletal muscle function. This adipose-skeletal
muscle crosstalk has been increasingly implicated in poor functional and metabolic outcomes in younger hu-
man populations. The unique contributions of AT structure and function and AT-secreted factors to mobility de-
cline and skeletal muscle function in the context of human aging have not been addressed. The proposed stud-
ies will fill a critical knowledge gap by directly assessing structural and functional components of AT in aging
and using their associations with mobility to identify AT-secreted proteins that negatively impact skeletal mus-
cle function. The long-term goal of this ancillary study is to leverage and add to the outstanding resources of
the parent SOMMA project to understand the contribution of AT quality, AT-secreted factors and AT-skeletal
muscle crosstalk to mobility disability and other complications of aging in humans. Our overall objective is to
identify key structural and functional components of AT quality - including necrosis, senescence, inflammation,
self-renewal and metabolic flexibility - and AT-secreted proteins that influence mobility via direct effects on
skeletal muscle. We hypothesize that AT structure and function influences AT-secreted proteins that contribute
to aging-related mobility outcomes by directly impacting skeletal muscle function. The stated purpose of Aim 1
is to determine which structural and functional components of AT are associated with slower walking speed.
We posit that increased cellular senescence, increased necrosis, increased inflammation, decreased capacity
for self-renewal and metabolic inflexibility will be associated with slower walking speed. For Aim 2, we antici-
pate that incubation of human muscle cells with known and novel secreted proteins - identified through stand-
ard immunoassay panels and unbiased proteomics and shown to be associated with aberrations in AT struc-
ture and/or function - will worsen mitochondrial respiration, increase oxidative stress, decrease contractility and
muscle cell diameter. This work will have a positive translational impact by improving strategies for prevention
and/or treatment of aging-related mobility disability and by promoting knowledge and facilitating future studies
to understanding AT-skeletal muscle crosstalk across the lifespan.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ERIN E. KERSHAW其他文献
ERIN E. KERSHAW的其他文献
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{{ truncateString('ERIN E. KERSHAW', 18)}}的其他基金
Investigating the role of adipose tissue in mobility and aging (SOMMA-AT)
研究脂肪组织在活动能力和衰老中的作用 (SOMMA-AT)
- 批准号:
10083347 - 财政年份:2020
- 资助金额:
$ 80.35万 - 项目类别:
Investigating the role of adipose tissue in mobility and aging (SOMMA-AT)
研究脂肪组织在活动能力和衰老中的作用 (SOMMA-AT)
- 批准号:
10453682 - 财政年份:2020
- 资助金额:
$ 80.35万 - 项目类别:
Investigating the role of adipose tissue in mobility and aging (SOMMA-AT)
研究脂肪组织在活动能力和衰老中的作用 (SOMMA-AT)
- 批准号:
10665695 - 财政年份:2020
- 资助金额:
$ 80.35万 - 项目类别:
Adipose Triglyceride Lipase (ATGL) in Lipotoxicity and The Metabolic Syndrome
脂肪甘油三酯脂肪酶 (ATGL) 在脂毒性和代谢综合征中的作用
- 批准号:
8016482 - 财政年份:2011
- 资助金额:
$ 80.35万 - 项目类别:
Adipose Triglyceride Lipase (ATGL) in Lipotoxicity and The Metabolic Syndrome
脂肪甘油三酯脂肪酶 (ATGL) 在脂毒性和代谢综合征中的作用
- 批准号:
8445405 - 财政年份:2011
- 资助金额:
$ 80.35万 - 项目类别:
Adipocyte lipolysis, adipose tissue function, and lipodystrophy
脂肪细胞脂肪分解、脂肪组织功能和脂肪营养不良
- 批准号:
9211580 - 财政年份:2011
- 资助金额:
$ 80.35万 - 项目类别:
Adipose Triglyceride Lipase (ATGL) in Lipotoxicity and The Metabolic Syndrome
脂肪甘油三酯脂肪酶 (ATGL) 在脂毒性和代谢综合征中的作用
- 批准号:
8214539 - 财政年份:2011
- 资助金额:
$ 80.35万 - 项目类别:
Contribution of ATGL in skeletal muscle to lipid metabolism and insulin action
骨骼肌中 ATGL 对脂质代谢和胰岛素作用的贡献
- 批准号:
7383915 - 财政年份:2007
- 资助金额:
$ 80.35万 - 项目类别:
Contribution of ATGL in skeletal muscle to lipid metabolism and insulin action
骨骼肌中 ATGL 对脂质代谢和胰岛素作用的贡献
- 批准号:
7240376 - 财政年份:2007
- 资助金额:
$ 80.35万 - 项目类别:
Contribution of ATGL in skeletal muscle to lipid metabolism and insulin action
骨骼肌中 ATGL 对脂质代谢和胰岛素作用的贡献
- 批准号:
7649793 - 财政年份:2007
- 资助金额:
$ 80.35万 - 项目类别:
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