The journals of gerontology. Series A, Biological sciences and medical sciences · 2026
Metabolomic profiling of telomere length: associations with aging-related phenotypes and modifiable lifestyle factors in Chinese older adults.
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Ma Tianpei, Zhao Xunying, Jiang Ke, Lin Lei, Xu Lanjin, Yang Nan, Chen Xin, Zhao Qingwen, Zhang Xingyu, Yan Haiyu, Dui Xinyang, Xiao Jinyu, Fan Mengyu, Long Lu, Liao Jiaqiang, Zhang Tao, Jiang Xia, Li Jiayuan
Аннотация
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 5957 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.
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 5957 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.