A blood aging clock defines disease-induced deviation from healthy molecular aging.
- 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, Jiangsu, China.
- 2Department of Computer Science, RWTH Aachen University, Ahornstr. 55, Aachen 52074, Germany.
- 3School of Pharmacy, The University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
Abstract
Aging shapes disease susceptibility and recovery, yet it remains unclear whether disease-induced molecular perturbations can be quantitatively mapped onto healthy aging trajectories. Here, we integrated 10 753 whole-blood transcriptomic profiles from 23 cohorts and developed a blood aging predictor (BAP) using 5808 healthy individuals to define a reference trajectory of blood molecular aging. Applying BAP to COVID-19 revealed marked transcriptomic age acceleration (AgeAccel), with patients showing an average AgeAccel of 9.34 years after cohort-specific baseline correction. This aging-referenced deviation occurred across age groups and was associated with interferon signaling, immune-inflammatory activation, cytokine and neutrophil-related programs, DNA damage responses, proteostasis stress, and impaired cellular quality-control pathways. Longitudinal analysis showed that AgeAccel increased during acute infection but declined during recovery, indicating a potentially reversible aging-like molecular state at the cohort level rather than irreversible aging. Extension to sepsis, influenza, and major depressive disorder further demonstrated that elevated AgeAccel captures disease-associated molecular burden across distinct pathological contexts. Together, our study redefines transcriptomic AgeAccel as an interpretable measure of disease-induced deviation from healthy molecular homeostasis and provides a quantitative framework for assessing systemic disease burden and recovery dynamics from peripheral blood transcriptomes.
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BibTeX
@article{li2026blood,
title = {{A blood aging clock defines disease-induced deviation from healthy molecular aging.}},
author = {Haotian Li and Sai Liu and Zheng Zhou and Qiulun Lu and Guangji Wang and Zheying Zhu and Xinuo Li},
journal = {Briefings in bioinformatics},
year = {2026},
month = sep,
doi = {10.1093/bib/bbag605},
url = {https://europepmc.org/article/MED/42960996},
note = {CC BY},
}
RIS
TY - JOUR
TI - A blood aging clock defines disease-induced deviation from healthy molecular aging.
AU - Haotian Li
AU - Sai Liu
AU - Zheng Zhou
AU - Qiulun Lu
AU - Guangji Wang
AU - Zheying Zhu
AU - Xinuo Li
PY - 2026
DA - 2026/09/01
JO - Briefings in bioinformatics
DO - 10.1093/bib/bbag605
UR - https://europepmc.org/article/MED/42960996
AB - Aging shapes disease susceptibility and recovery, yet it remains unclear whether disease-induced molecular perturbations can be quantitatively mapped onto healthy aging trajectories. Here, we integrated 10 753 whole-blood transcriptomic profiles from 23 cohorts and developed a blood aging predictor (BAP) using 5808 healthy individuals to define a reference trajectory of blood molecular aging. Applying BAP to COVID-19 revealed marked transcriptomic age acceleration (AgeAccel), with patients showing an average AgeAccel of 9.34 years after cohort-specific baseline correction. This aging-referenced deviation occurred across age groups and was associated with interferon signaling, immune-inflammatory activation, cytokine and neutrophil-related programs, DNA damage responses, proteostasis stress, and impaired cellular quality-control pathways. Longitudinal analysis showed that AgeAccel increased during acute infection but declined during recovery, indicating a potentially reversible aging-like molecular state at the cohort level rather than irreversible aging. Extension to sepsis, influenza, and major depressive disorder further demonstrated that elevated AgeAccel captures disease-associated molecular burden across distinct pathological contexts. Together, our study redefines transcriptomic AgeAccel as an interpretable measure of disease-induced deviation from healthy molecular homeostasis and provides a quantitative framework for assessing systemic disease burden and recovery dynamics from peripheral blood transcriptomes.
SN - 1467-5463
SN - 1477-4054
ER -