Research Paper|Volume 17, Issue 5|pp 1206—1220

Changes in metabolism-related RNA expression in circulating white blood cells of aged individual with physical frailty

Yuka Okinaka¹, Yoshihito Suda^1,², Tomoyuki Matsumoto², Ryosuke Kuroda², Yoshiyuki Shinagawa^1,³, Sheraz Gul^4,⁵, Carsten Claussen^4,⁵, Ikuko Matsui⁶, Yutaka Matsui⁶, Akihiko Taguchi¹

¹Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo 650-0047, Japan
²Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0019, Japan
³Global Planning Group, Kaneka corporation, Osaka-shi, Osaka 530-8288, Japan
⁴Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Hamburg 22525, Germany
⁵Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Hamburg 22525, Germany
⁶Matsui Dietary and Dementia Clinic, Akashi-shi, Hyogo 673-0891, Japan

Received: November 26, 2024Accepted: May 7, 2025Published: May 28, 2025

https://doi.org/10.18632/aging.206256

Copyright: © 2025 Okinaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Physical frailty is an age-related clinical condition associated with deterioration of physiological capacity. In aged mice, increased RNA expression of metabolism-related genes in circulating white blood cells (WBC) correlates with impaired physical function.

Methods: Twenty elderly volunteers were enrolled in this exploratory analysis and the possible link between RNA expression of metabolism-related genes in WBC and impairment of their physical function was investigated (jRCT1050210166. Feb. 02, 2022). In mechanism of action studies, cellular interactions between WBC and cells in muscle tissue were investigated in mice.

Results: RNA expression of metabolism-related genes, such as glucose transporter 1 (Glut1), Glut3, AMP-activated protein kinase A, and prolyl hydroxylase 3, was significantly increased in aged individuals with swallowing dysfunction and masticatory disturbance compared to those without these symptoms. The level of metabolism-related RNA expression significantly decreased with walking habits compared to no walking habits. Studies in mice have revealed a direct link between circulating WBC and endothelium/satellite cells via gap junction.

Conclusions: Our results indicate that the level of metabolism-related RNA expression in WBC can serve as a marker of impaired physical function in the elderly and that circulating WBC may have a previously unknown physiological role in maintaining physical function.