Blood Proteomic Biomarkers indicate reduced system and tissue level inflammation responses to The GOTO Lifestyle Intervention in Older Adults

The effects of lifestyle interventions on the blood metabolome and transcriptome are well studied, but the interplay between tissues is not well understood. In a multi-omics multi-tissue design we study how the serum proteome reflects health improvements in age-related deficits such as body composition, fat and glucose metabolism and low-grade inflammation in older adults undergoing a 13-week lifestyle intervention (GOTO trial). Significant intervention effects on the fasting blood proteome were observed in both sexes, with downregulated immune-related pathways, including the complement system, inflammation, cholesterol transport and coagulation. These findings associated with improved body composition and immune-metabolic health markers. In addition, we found that the intervention-induced changes in the transcriptome of muscle and subcutaneous adipose tissue (SAT) biopsies were correlated with changes of the corresponding circulating proteins. The most notable correlations were observed for proteins involved in inflammatory processes and corresponding gene expression in the SAT. Our findings emphasize the broad beneficial effects of moderate lifestyle interventions in older adults and how circulating proteins such as FN1, LGALS3BP and PRG4 reflect the immune-metabolic health benefits.