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

IF 7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Molecular Metabolism Pub Date : 2025-07-15 DOI:10.1016/j.molmet.2025.102213

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

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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 in silico. Additionally, novel ASAT-secreted proteins such as NID2 and APOA4 were implicated in mediating ASAT crosstalk with skeletal muscle and brain in silico. 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.

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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。

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然知之甚少。在这里，利用ASAT转录组学和外植体条件培养基蛋白质组学，来自肌肉、运动和衰老研究(SOMMA；年龄≥70岁，n=229)，我们发现ASAT基因簇和分泌蛋白与老年人身体和认知功能的综合评估密切相关。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能力限制的关键标志。系统遗传学分析证实了分泌- serinf1是骨骼肌收缩的负调节因子，并强调了其在心脏炎症诱导中的潜在作用。此外，新的ASAT分泌蛋白如NID2和APOA4在硅中介导骨骼肌和脑的ASAT串扰。我们的框架提供了对老年人身体和认知表现背后的ASAT驱动的组织串扰的见解，并为理解ASAT在人类衰老中的作用提供了宝贵的资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

14.50

自引率

2.50%

发文量

219

审稿时长

43 days

期刊介绍： Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction. We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.