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皮下脂肪组织分泌蛋白作为老年人身体和认知功能的内分泌调节因子

Subcutaneous Adipose Tissue-Secreted Proteins as Endocrine Regulators of Physical and Cognitive Function in Older Adults.

作者信息

Sparks Lauren, Ahn Cheehoon, Tamburini Ian, Sanford James, Zhou Mingqi, Gamie Farah, Yeo Reichelle, Viesi Carlos, Pino Maria, Whytock Katie, Oberlin Lauren, Mau Theresa, Adkins Joshua, Justice Jamie, Wood Ashlee, Ross Zana, Piehowski Paul, Bunch Chelsea Hutchinson, Erickson Kirk I, Toledo Frederico, Lane Nancy, Cawthon Peggy, Newman Anne, Kritchevsky Stephen, Cummings Steven, Goodpaster Bret, Kershaw Erin, Seldin Marcus

机构信息

Translational Research Institute, AdventHealth.

Advent Health.

出版信息

Res Sq. 2025 Jun 3:rs.3.rs-6498803. doi: 10.21203/rs.3.rs-6498803/v1.

DOI:10.21203/rs.3.rs-6498803/v1
PMID:40502786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12155204/
Abstract

Declines in skeletal muscle and cognitive function in older adults have been linked to abnormalities in abdominal subcutaneous adipose tissue (ASAT), yet the underlying molecular mediators remain poorly understood. Here, leveraging ASAT transcriptomics and explant-conditioned media proteomics from participants in the Study of Muscle, Mobility and Aging (SOMMA; age ≥70 years, n = 229), we identified ASAT gene clusters and secreted proteins strongly associated with comprehensive assessments of physical and cognitive function in older adults. ASAT inflammation and secreted immunoglobulins were identified as key signatures of aging-associated physical and cognitive performance limitations. Systems genetics analysis confirmed secreted-SERPINF1 as a negative regulator of skeletal muscle contraction and highlighted its potential role in inducing inflammation in the heart . Additionally, novel ASAT-secreted proteins such as NID2 and APOA4 were implicated in mediating ASAT crosstalk with skeletal muscle and brain . Our framework provides insights into ASAT-driven tissue crosstalk underlying physical and cognitive performance in older adults and offers a valuable resource for understanding the role of ASAT in human aging.

摘要

老年人骨骼肌和认知功能的下降与腹部皮下脂肪组织（ASAT）异常有关，但潜在的分子介质仍知之甚少。在此，我们利用肌肉、运动与衰老研究（SOMMA；年龄≥70岁，n = 229）参与者的ASAT转录组学和外植体条件培养基蛋白质组学，确定了与老年人身体和认知功能综合评估密切相关的ASAT基因簇和分泌蛋白。ASAT炎症和分泌的免疫球蛋白被确定为与衰老相关的身体和认知表现限制的关键特征。系统遗传学分析证实分泌型丝氨酸蛋白酶抑制剂F1（SERPINF1）是骨骼肌收缩的负调节因子，并突出了其在诱导心脏炎症中的潜在作用。此外，新型ASAT分泌蛋白如NID2和APOA4参与介导ASAT与骨骼肌和大脑的相互作用。我们的框架为ASAT驱动的组织相互作用提供了见解，这种相互作用是老年人身体和认知表现的基础，并为理解ASAT在人类衰老中的作用提供了宝贵资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/c8a2e5bbb054/nihpp-rs6498803v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/4194c86f4e45/nihpp-rs6498803v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/794b895cc3e4/nihpp-rs6498803v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/35e554a5a02a/nihpp-rs6498803v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/b41e3fbc652d/nihpp-rs6498803v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/a6ed9a2286e7/nihpp-rs6498803v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/c8a2e5bbb054/nihpp-rs6498803v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/4194c86f4e45/nihpp-rs6498803v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/794b895cc3e4/nihpp-rs6498803v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/35e554a5a02a/nihpp-rs6498803v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/b41e3fbc652d/nihpp-rs6498803v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/a6ed9a2286e7/nihpp-rs6498803v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fa/12155204/c8a2e5bbb054/nihpp-rs6498803v1-f0006.jpg

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本文引用的文献

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Plasma proteomics identify biomarkers and undulating changes of brain aging.血浆蛋白质组学可识别脑衰老的生物标志物及波动变化。
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Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.
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