A plasma metabolite signature (Met-TL) comprising 26 metabolites explaining 17.5% of telomere length variance was identified and found to significantly associate with aging-related phenotypes and modifiable lifestyle factors, with particularly robust associations with steatohepatitis and hepatic biomarkers, partially mediating the protective association between healthy lifestyle and steatohepatitis.
Key Findings
Results
A plasma metabolite signature (Met-TL) comprising 26 metabolites was identified that explains 17.5% of telomere length variance.
Telomere length 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 were identified through elastic net regression models.
The 26-metabolite signature collectively explained 17.5% of TL variance.
Results
Met-TL was significantly associated with aging-related phenotypes, yielding 44 Bonferroni-corrected associations.
Associations between Met-TL and aging-related phenotypes were evaluated using linear and logistic regression models in a larger, non-overlapping sample of 5,957 WCHAC participants.
A total of 44 Bonferroni-corrected significant associations were found between Met-TL and aging-related phenotypes.
Associations were evaluated using both linear and logistic regression models.
Results
Met-TL was significantly associated with 4 modifiable lifestyle factors.
Modifiable lifestyle factor associations were evaluated in the larger non-overlapping sample of 5,957 WCHAC participants.
Four statistically significant associations were identified between Met-TL and modifiable lifestyle factors.
Associations were evaluated using linear and logistic regression models.
Results
Met-TL showed robust associations with steatohepatitis and hepatic biomarkers.
The associations with steatohepatitis and hepatic biomarkers were described as 'notably' robust among all aging-related phenotype associations.
This finding suggests Met-TL may be particularly useful for identifying liver dysfunction.
The association was evaluated in the non-overlapping sample of 5,957 participants using logistic regression.
Results
Met-TL partially mediated the protective association between healthy lifestyle and steatohepatitis, with a mediation proportion of 8.2%.
Mediation analysis was employed to explore the mediating effects of Met-TL between lifestyle factors and aging-related diseases.
The mediation proportion of Met-TL between healthy lifestyle and steatohepatitis was 8.2%.
The mediation was described as 'partial,' indicating that Met-TL explains part but not all of the lifestyle-steatohepatitis relationship.
Methods
The study population consisted of Chinese older adults from the West China Health and Aging Cohort (WCHAC), with metabolomic profiling conducted in a subsample and validation in a larger non-overlapping sample.
Metabolomic profiling and TL measurement were conducted in 282 participants.
Associations with aging-related phenotypes and lifestyle factors were evaluated in a separate, non-overlapping sample of 5,957 WCHAC participants.
The two-sample design allowed for discovery and validation-like assessment without sample overlap.
What This Means
This research suggests that a specific pattern of 26 molecules found in the blood (called a metabolite signature, or Met-TL) is linked to telomere length — the protective caps on chromosomes that shorten as cells age. Researchers measured telomeres and blood metabolites in 282 older Chinese adults, then tested whether this metabolite pattern was associated with health conditions and lifestyle habits in nearly 6,000 additional older adults. They found that the Met-TL signature was significantly associated with 44 aging-related health measures and 4 lifestyle factors, with particularly strong connections to liver disease (steatohepatitis) and liver health markers.
One notable finding is that this metabolite signature partially explains why people with healthier lifestyles are less likely to develop steatohepatitis (fatty liver disease with inflammation) — accounting for about 8.2% of that protective relationship. This means that part of the benefit of a healthy lifestyle for liver health may work through changes in these blood metabolites that are also connected to cellular aging processes.
This research suggests that measuring this metabolite pattern in the blood could potentially serve as a practical indicator of biological aging, especially for detecting early liver problems, without the need to directly measure telomere length. The findings open the door to personalized monitoring of aging and development of targeted interventions, though further research in diverse populations would be needed to confirm and extend these results.
Ma T, Zhao X, Jiang K, Lin L, Xu L, Yang N, et al.. (2026). Metabolomic profiling of telomere length: associations with aging-related phenotypes and modifiable lifestyle factors in Chinese older adults.. The journals of gerontology. Series A, Biological sciences and medical sciences. https://doi.org/10.1093/gerona/glag209