GDF15 as a biomarker of ageing

Abstract

The ageing process is accompanied by the gradual development of chronic systemic inflammation (inflamm-ageing). Growth differentiation factor 15 (GDF15) is associated with inflammation and known to be a stress-induced factor. The present study aimed to explore the association of GDF15 with ageing. In this cross-sectional study, serum GDF15, hematological parameters, and biomedical parameters were determined in 120 healthy individuals (23-83 years old, males). Three telomere related parameters, including telomere length, telomerase activity, and the expression of human telomerase reverse transcriptase (hTERT) mRNA were also quantified. Our results showed that the older group has a higher levels of GDF15 and lower expression of hTERT mRNA, and PBMC telomerase activity (p < 0.001). In individuals with high GDF15 levels, they were older, and presented with the lower level of hTERT mRNA and T/S ratio (p < 0.01). Spearman correlation analysis shows that GDF15 positively correlated with age (r = 0.664, p < 0.001), and negatively correlated with telomere length (r = -0.434, p < 0.001), telomerase activity (r = -0.231, p = 0.012), and hTERT mRNA (r = -0.206, p = 0.024). Furthermore, in multivariate regression analysis, GDF15 levels showed a statistically significant linear and negative relationship with PBMC telomerase activity (β-coefficient = -0.583, 95% CI -1.044 to -0.122, p = 0.014), telomere length (β-coefficient = -0.200, 95% CI -0.305 to -0.094, p < 0.001), and hTERT mRNA (β-coefficient = -0.207, 95% CI -0.312 to -0.102, p < 0.001) after adjusting for confounders. These results support that circulating GDF15 is the potential biomarker of ageing that may influence the risk and progression of multiple ageing conditions.

Keywords: Ageing; Growth differentiation factor 15; Telomerase activity; Telomere length; hTERT.