Metabolomic Profiling of Telomere Length: Associations with Aging-related Phenotypes and Modifiable Lifestyle Factors in Chinese Older Adults

BACKGROUND: Telomere length (TL) is a well-established biomarker of cellular senescence, yet the metabolic profile of TL and its associations with aging-related phenotypes and responses to modifiable lifestyle factors remain unclear. METHODS: TL was measured using quantitative real-time polymerase chain reaction (qPCR) in 282 participants from the West China Health and Aging Cohort (WCHAC). Plasma metabolites were analyzed using Liquid Chromatography-tandem Mass Spectrometry. TL-associated metabolic signatures (Met-TL) were identified through elastic net regression models. Associations between Met-TL and aging-related phenotypes and modifiable lifestyle factors were evaluated using linear and logistic regression models in a larger, non-overlapping sample of 5,957 WCHAC participants. Furthermore, we employed mediation analysis to explore the mediating effects of Met-TL between lifestyle factors and aging-related diseases. RESULTS: We identified a plasma metabolite signature comprising 26 metabolites explaining 17.5% of TL variance. Met-TL significantly associated with aging-related phenotypes (44 Bonferroni-corrected associations) and modifiable lifestyle factors (4 associations). Notably, Met-TL showed robust associations with steatohepatitis and hepatic biomarkers. Mediation analysis revealed that Met-TL partially explained the protective association between healthy lifestyle and steatohepatitis, with a mediation proportion of 8.2%. CONCLUSION: These findings provide novel insights into the metabolic profile of TL in older adults. The Met-TL may serve as a promising biomarker of cellular aging, particularly in identifying liver dysfunction, facilitating the development of personalized aging monitoring and anti-aging intervention strategies.