Long-lived proteins and DNA as candidate predictive biomarkers for tissue associated diseases

Xiaosong Liu; Bozidar Novak; Christian Namendorf; Barbara Steigenberger; Yaoyang Zhang; Christoph W Turck

doi:10.1016/j.isci.2024.109642

Long-lived proteins and DNA as candidate predictive biomarkers for tissue associated diseases

iScience. 2024 Mar 28;27(4):109642. doi: 10.1016/j.isci.2024.109642. eCollection 2024 Apr 19.

Authors

Xiaosong Liu^{1

2}, Bozidar Novak³, Christian Namendorf⁴, Barbara Steigenberger⁵, Yaoyang Zhang¹, Christoph W Turck^{3

6

7}

Affiliations

¹ Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Road, Shanghai 201210, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Max Planck Institute of Psychiatry, Proteomics and Biomarkers, Kraepelinstr. 2-10, 80804 Munich, Germany.
⁴ Max Planck Institute of Psychiatry, Clinical Laboratory, Core Unit Analytics and Mass Spectrometry, Kraepelinstr. 2-10, 80804 Munich, Germany.
⁵ Mass Spectrometry Core Facility, Max Planck Institute of Biochemistry, D-82152 Martinsried/Munich, Germany.
⁶ Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
⁷ National Resource Center for Non-human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, China.

Abstract

Protein turnover is an important mechanism to maintain proteostasis. Long-lived proteins (LLPs) are vulnerable to lose their function due to time-accumulated damages. In this study we employed in vivo stable isotope labeling in mice from birth to postnatal day 89. Quantitative proteomics analysis of ten tissues and plasma identified 2113 LLPs, including widespread and tissue-specific ones. Interestingly, a significant percentage of LLPs was detected in plasma, implying a potential link to age-related cardiovascular diseases. LLPs identified in brains were related to neurodegenerative diseases. In addition, the relative quantification of DNA-derived deoxynucleosides from the same tissues provided information about cellular DNA renewal and showed good correlation with LLPs in the brain. The combined data reveal tissue-specific maps of mouse LLPs that may be involved in pathology due to a low renewal rate and an increased risk of damage. Tissue-derived peripheral LLPs hold promise as biomarkers for aging and age-related diseases.

Keywords: Disease; Protein; Proteomics; Systems biology.