Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia
Abstract Background: Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk. Methods: We used t...
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Nature Portfolio
2025-08-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-01096-y |
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| author | Sanaz Sedaghat Saeun Park Rob F. Walker Shuo Wang Jialing Liu Timothy M. Hughes Behnam Sabayan Weihong Tang Josef Coresh James S. Pankow Keenan A. Walker Ramon Casanova Ruth Dubin Rajat Deo Jerome I. Rotter Alexis C. Wood Peter Ganz Pamela L. Lutsey Weihua Guan Anna Prizment |
| author_facet | Sanaz Sedaghat Saeun Park Rob F. Walker Shuo Wang Jialing Liu Timothy M. Hughes Behnam Sabayan Weihong Tang Josef Coresh James S. Pankow Keenan A. Walker Ramon Casanova Ruth Dubin Rajat Deo Jerome I. Rotter Alexis C. Wood Peter Ganz Pamela L. Lutsey Weihua Guan Anna Prizment |
| author_sort | Sanaz Sedaghat |
| collection | DOAJ |
| description | Abstract Background: Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk. Methods: We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, n = 11,758) and late-life (mean age: 77 years, 56% female, n = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third of participants. Proteomics-based age acceleration (PAA) was calculated as residuals after regressing PACs on chronological age. We validated the midlife PAC in the MESA cohort (mean age: 62 years, 52% female, n = 5829). We used multivariable linear and Cox proportional hazards regression to assess the association of PAA with cognitive function and dementia incidence, respectively. Results: In ARIC, every five years, PAA is associated with lower global cognition: difference: −0.11, 95% confidence interval[CI]: −0.16, −0.06) using midlife PAA and difference: −0.17, CI: −0.23, −0.12 using late-life PAA. Midlife PAA is associated with higher dementia risk (hazard ratio[HR]: 1.20 [CI: 1.04, 1.36]) and more prominently when using late-life PAA (HR: 2.14 [CI:1.67, 2.73]). Similar findings are observed in MESA: PAA is associated with lower global cognitive function (difference: −0.08 [CI: −0.14, −0.03]) and higher dementia risk (HR:1.23 [CI: 1.04, 1.46]). Conclusions Accelerated biological age is associated with lower cognition and a higher risk of dementia in midlife and more prominently in late life. |
| format | Article |
| id | doaj-art-91c0c4792ceb40f9a834f95603535c81 |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Communications Medicine |
| spelling | doaj-art-91c0c4792ceb40f9a834f95603535c812025-08-20T03:46:29ZengNature PortfolioCommunications Medicine2730-664X2025-08-015111010.1038/s43856-025-01096-yProteomics-based aging clocks in midlife or late-life and their associated risk of dementiaSanaz Sedaghat0Saeun Park1Rob F. Walker2Shuo Wang3Jialing Liu4Timothy M. Hughes5Behnam Sabayan6Weihong Tang7Josef Coresh8James S. Pankow9Keenan A. Walker10Ramon Casanova11Ruth Dubin12Rajat Deo13Jerome I. Rotter14Alexis C. Wood15Peter Ganz16Pamela L. Lutsey17Weihua Guan18Anna Prizment19Division of Epidemiology and Community Health, School of Public Health, University of MinnesotaDivision of Epidemiology and Community Health, School of Public Health, University of MinnesotaDivision of Epidemiology and Community Health, School of Public Health, University of MinnesotaDepartment of Laboratory Medicine and Pathology, Medical School, University of MinnesotaDivision of Biostatistics and Health Data Science, School of Public Health, University of MinnesotaWake Forest University School of MedicineDivision of Epidemiology and Community Health, School of Public Health, University of MinnesotaDivision of Epidemiology and Community Health, School of Public Health, University of MinnesotaDepartments of Population Health and Medicine, NYU Glossman School of MedicineDivision of Epidemiology and Community Health, School of Public Health, University of MinnesotaLaboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on AgingDepartment of Biostatistics and Data Science, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Division of Nephrology, University of Texas Southwestern Medical CenterDivision of Cardiovascular Medicine, Perelman School of Medicine, University of PennsylvaniaInstitute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation; Department of Pediatrics, Harbor-UCLA Medical CenterUS Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center, Baylor College of MedicineDivision of Cardiology, Zuckerberg San Francisco General Hospital and Department of Medicine, University of CaliforniaDivision of Epidemiology and Community Health, School of Public Health, University of MinnesotaDivision of Biostatistics and Health Data Science, School of Public Health, University of MinnesotaDepartment of Laboratory Medicine and Pathology, Medical School, University of MinnesotaAbstract Background: Biological age can be quantified by composite proteomic scores, called proteomics-based aging clocks (PACs). We investigated whether a discrepancy between chronological and biological age in midlife and late-life is associated with cognition and dementia risk. Methods: We used two longitudinal population-based studies: the Atherosclerosis Risk in Communities (ARIC) Study and the Multi-Ethnic Study of Atherosclerosis (MESA). PACs were created in ARIC at midlife (mean age: 58 years, 57% female, n = 11,758) and late-life (mean age: 77 years, 56% female, n = 4934) using elastic net regression models in two-thirds of dementia-free participants and validated in the remaining one-third of participants. Proteomics-based age acceleration (PAA) was calculated as residuals after regressing PACs on chronological age. We validated the midlife PAC in the MESA cohort (mean age: 62 years, 52% female, n = 5829). We used multivariable linear and Cox proportional hazards regression to assess the association of PAA with cognitive function and dementia incidence, respectively. Results: In ARIC, every five years, PAA is associated with lower global cognition: difference: −0.11, 95% confidence interval[CI]: −0.16, −0.06) using midlife PAA and difference: −0.17, CI: −0.23, −0.12 using late-life PAA. Midlife PAA is associated with higher dementia risk (hazard ratio[HR]: 1.20 [CI: 1.04, 1.36]) and more prominently when using late-life PAA (HR: 2.14 [CI:1.67, 2.73]). Similar findings are observed in MESA: PAA is associated with lower global cognitive function (difference: −0.08 [CI: −0.14, −0.03]) and higher dementia risk (HR:1.23 [CI: 1.04, 1.46]). Conclusions Accelerated biological age is associated with lower cognition and a higher risk of dementia in midlife and more prominently in late life.https://doi.org/10.1038/s43856-025-01096-y |
| spellingShingle | Sanaz Sedaghat Saeun Park Rob F. Walker Shuo Wang Jialing Liu Timothy M. Hughes Behnam Sabayan Weihong Tang Josef Coresh James S. Pankow Keenan A. Walker Ramon Casanova Ruth Dubin Rajat Deo Jerome I. Rotter Alexis C. Wood Peter Ganz Pamela L. Lutsey Weihua Guan Anna Prizment Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia Communications Medicine |
| title | Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia |
| title_full | Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia |
| title_fullStr | Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia |
| title_full_unstemmed | Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia |
| title_short | Proteomics-based aging clocks in midlife or late-life and their associated risk of dementia |
| title_sort | proteomics based aging clocks in midlife or late life and their associated risk of dementia |
| url | https://doi.org/10.1038/s43856-025-01096-y |
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