Plasma microRNA signatures of aging and their links to health outcomes and mortality: findings from a population-based cohort study
Abstract Background MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomar...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Genome Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13073-025-01437-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849432691929251840 |
|---|---|
| author | Lieke M. Kuiper Michelle M. J. Mens Julia W. Wu Jaap Goudsmit Yuan Ma Liming Liang Albert Hofman Trudy Voortman M. Arfan Ikram Jeroen G. J. van Rooij Joyce B. J. van Meurs Mohsen Ghanbari |
| author_facet | Lieke M. Kuiper Michelle M. J. Mens Julia W. Wu Jaap Goudsmit Yuan Ma Liming Liang Albert Hofman Trudy Voortman M. Arfan Ikram Jeroen G. J. van Rooij Joyce B. J. van Meurs Mohsen Ghanbari |
| author_sort | Lieke M. Kuiper |
| collection | DOAJ |
| description | Abstract Background MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomarkers for healthy aging and age-related diseases. This study aimed to explore plasma extracellular microRNAs as a biological aging indicator and their associations with health outcomes using population-level data. Methods We quantified plasma expression levels of 2083 extracellular microRNAs using targeted RNA-sequencing in 2684 participants from the population-based Rotterdam Study cohort. The training and test sets included 1930 participants from the advanced-aged initial and second subcohort (RS-I/RS-II; median age: 70.6), while the validation set comprised 754 participants from the middle-aged fourth subcohort (RS-IV; median age: 53.5). Based on 591 microRNAs well-expressed in plasma, we examined differential expression of microRNAs with chronological age, PhenoAge—a composite score of age and nine multi-system blood biomarkers—the frailty index, and mortality. Next, elastic net models were employed to construct composite microRNA-based aging biomarkers predicting chronological age (mirAge), PhenoAge (mirPA), frailty index (mirFI), and mortality (mirMort). The association of these aging biomarkers with different age-related health outcomes was assessed using Cox Proportional Hazard, linear regression, and logistic regression models in the test and validation sets. Results We identified 188 microRNAs differentially expressed with chronological age within the RS-I/RS-II advanced-aged population (n training = 1158, n test = 772), of which 177 microRNAs (94.1%) were replicated in the middle-aged RS-IV subcohort (n validation = 754). Moreover, 227 miRNAs showed robust associations with PhenoAge, 61 with FI, and 16 with 10-year mortality independent of chronological age. Subsequently, we constructed four plasma microRNA-based aging biomarkers: mirAge with 108, mirPA with 153, mirFI with 81, and mirMort with 50 miRNAs. Elevated scores on these microRNA-based aging biomarkers were associated with unfavorable health outcomes, including lower subjective physical functioning and self-reported health and increased mortality and frailty risk, but not with first- or multi-morbidity. Overall, larger effect estimates were observed for mirPA, mirFI, and mirMort compared to mirAge. Conclusions This study describes distinct plasma microRNA-aging signatures and introduces four microRNA-based aging biomarkers with the potential to identify accelerated aging and age-related decline, providing insights into the intricate process of human aging. |
| format | Article |
| id | doaj-art-cadcaf74e95949a6bbddf3b3690890ec |
| institution | Kabale University |
| issn | 1756-994X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj-art-cadcaf74e95949a6bbddf3b3690890ec2025-08-20T03:27:18ZengBMCGenome Medicine1756-994X2025-06-0117111410.1186/s13073-025-01437-5Plasma microRNA signatures of aging and their links to health outcomes and mortality: findings from a population-based cohort studyLieke M. Kuiper0Michelle M. J. Mens1Julia W. Wu2Jaap Goudsmit3Yuan Ma4Liming Liang5Albert Hofman6Trudy Voortman7M. Arfan Ikram8Jeroen G. J. van Rooij9Joyce B. J. van Meurs10Mohsen Ghanbari11Department of Internal Medicine, Erasmus MC University Medical CenterDepartment of Epidemiology, Erasmus MC University Medical CenterDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthDepartment of Epidemiology, Erasmus MC University Medical CenterDepartment of Epidemiology, Erasmus MC University Medical CenterDepartment of Internal Medicine, Erasmus MC University Medical CenterDepartment of Internal Medicine, Erasmus MC University Medical CenterDepartment of Epidemiology, Erasmus MC University Medical CenterAbstract Background MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomarkers for healthy aging and age-related diseases. This study aimed to explore plasma extracellular microRNAs as a biological aging indicator and their associations with health outcomes using population-level data. Methods We quantified plasma expression levels of 2083 extracellular microRNAs using targeted RNA-sequencing in 2684 participants from the population-based Rotterdam Study cohort. The training and test sets included 1930 participants from the advanced-aged initial and second subcohort (RS-I/RS-II; median age: 70.6), while the validation set comprised 754 participants from the middle-aged fourth subcohort (RS-IV; median age: 53.5). Based on 591 microRNAs well-expressed in plasma, we examined differential expression of microRNAs with chronological age, PhenoAge—a composite score of age and nine multi-system blood biomarkers—the frailty index, and mortality. Next, elastic net models were employed to construct composite microRNA-based aging biomarkers predicting chronological age (mirAge), PhenoAge (mirPA), frailty index (mirFI), and mortality (mirMort). The association of these aging biomarkers with different age-related health outcomes was assessed using Cox Proportional Hazard, linear regression, and logistic regression models in the test and validation sets. Results We identified 188 microRNAs differentially expressed with chronological age within the RS-I/RS-II advanced-aged population (n training = 1158, n test = 772), of which 177 microRNAs (94.1%) were replicated in the middle-aged RS-IV subcohort (n validation = 754). Moreover, 227 miRNAs showed robust associations with PhenoAge, 61 with FI, and 16 with 10-year mortality independent of chronological age. Subsequently, we constructed four plasma microRNA-based aging biomarkers: mirAge with 108, mirPA with 153, mirFI with 81, and mirMort with 50 miRNAs. Elevated scores on these microRNA-based aging biomarkers were associated with unfavorable health outcomes, including lower subjective physical functioning and self-reported health and increased mortality and frailty risk, but not with first- or multi-morbidity. Overall, larger effect estimates were observed for mirPA, mirFI, and mirMort compared to mirAge. Conclusions This study describes distinct plasma microRNA-aging signatures and introduces four microRNA-based aging biomarkers with the potential to identify accelerated aging and age-related decline, providing insights into the intricate process of human aging.https://doi.org/10.1186/s13073-025-01437-5MicroRNAAgingBiomarkerBiological ageMortalityFrailty |
| spellingShingle | Lieke M. Kuiper Michelle M. J. Mens Julia W. Wu Jaap Goudsmit Yuan Ma Liming Liang Albert Hofman Trudy Voortman M. Arfan Ikram Jeroen G. J. van Rooij Joyce B. J. van Meurs Mohsen Ghanbari Plasma microRNA signatures of aging and their links to health outcomes and mortality: findings from a population-based cohort study Genome Medicine MicroRNA Aging Biomarker Biological age Mortality Frailty |
| title | Plasma microRNA signatures of aging and their links to health outcomes and mortality: findings from a population-based cohort study |
| title_full | Plasma microRNA signatures of aging and their links to health outcomes and mortality: findings from a population-based cohort study |
| title_fullStr | Plasma microRNA signatures of aging and their links to health outcomes and mortality: findings from a population-based cohort study |
| title_full_unstemmed | Plasma microRNA signatures of aging and their links to health outcomes and mortality: findings from a population-based cohort study |
| title_short | Plasma microRNA signatures of aging and their links to health outcomes and mortality: findings from a population-based cohort study |
| title_sort | plasma microrna signatures of aging and their links to health outcomes and mortality findings from a population based cohort study |
| topic | MicroRNA Aging Biomarker Biological age Mortality Frailty |
| url | https://doi.org/10.1186/s13073-025-01437-5 |
| work_keys_str_mv | AT liekemkuiper plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT michellemjmens plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT juliawwu plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT jaapgoudsmit plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT yuanma plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT limingliang plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT alberthofman plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT trudyvoortman plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT marfanikram plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT jeroengjvanrooij plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT joycebjvanmeurs plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy AT mohsenghanbari plasmamicrornasignaturesofagingandtheirlinkstohealthoutcomesandmortalityfindingsfromapopulationbasedcohortstudy |