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

TL;DR

This study explores how proteins secreted by abdominal fat in older adults influence muscle and cognitive function, revealing new molecular links to aging-related decline.

Contribution

The study identifies novel ASAT-secreted proteins and gene clusters associated with physical and cognitive performance in older adults.

Findings

ASAT inflammation and secreted immunoglobulins are linked to physical and cognitive performance limitations in aging.

Secreted SERPINF1 negatively regulates skeletal muscle contraction and may induce heart inflammation.

Proteins like NID2 and APOA4 mediate ASAT crosstalk with muscle and brain in silico.

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.

Figures