Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adults
Background: The impact of healthy lifestyles on epigenetic age acceleration (EAA) and mortality in middle-aged/ senior populations remains unclear. This study investigates associations between lifestyle factors, EAA biomarkers, and mortality risk. Method: The 2532 adults of 50 years or older that re...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | The Journal of Nutrition, Health and Aging |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1279770725001277 |
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| author | Xing-Ling Chen Qiang-Qiang Zhao Sheng-Rong Lin Xing-Ling He Xiao-Jiao Zhang Si-Jing Li Zi-Ru Li Jia-Hui Chen Hua Zhang Xiao-Fang Li Yue-Hui Zhou Hui-Li Liao Shu-Ning Sun Zhong-Qi Yang Shi-Hao Ni Lu Lu |
| author_facet | Xing-Ling Chen Qiang-Qiang Zhao Sheng-Rong Lin Xing-Ling He Xiao-Jiao Zhang Si-Jing Li Zi-Ru Li Jia-Hui Chen Hua Zhang Xiao-Fang Li Yue-Hui Zhou Hui-Li Liao Shu-Ning Sun Zhong-Qi Yang Shi-Hao Ni Lu Lu |
| author_sort | Xing-Ling Chen |
| collection | DOAJ |
| description | Background: The impact of healthy lifestyles on epigenetic age acceleration (EAA) and mortality in middle-aged/ senior populations remains unclear. This study investigates associations between lifestyle factors, EAA biomarkers, and mortality risk. Method: The 2532 adults of 50 years or older that registered in NHANES between 1999–2002.This study evaluated compares first- to third-generation epigenetic clocks (HannumAge, HorvathAge, PhenoAge, GrimAge2, DunedinPoAm) in predicting mortality risk associations between five lifestyle domains (diet, abdominal adiposity, physical activity, smoking, alcohol) and EAA were analyzed via multivariable regression, with mediation models testing EAA’s role in lifestyle-mortality relationships. Results: Survival curves results identified DunedinPoAm, GrimAge2AA, and PhenoAgeAA as robust biomarkers of accelerated biological aging, independent of chronological age. In multivariable linear regression models, full adherence to healthy behaviors reduced GrimAge2AA by β = −5.55 years, PhenoAgeAA by β = −2.64 years, and DunedinPoAm by β = −0.06 SD, with smoking cessation demonstrating the strongest GrimAge2AA attenuation (10.17 years). Stratified analyses revealed pronounced benefits: cancer patients adhering to healthy diets (β = −0.04 SD, P for interaction = 0.01) and hypertensive individuals reducing smoking (β = −0.05 SD, P for interaction = 0.04) showed significant EAA mitigation. The sensitivity analysis is consistent with the original results. Mediation analyses indicated GrimAge2AA accounted for 63.58% of lifestyle-survival associations, DunedinPoAm (44.63%) and PhenoAgeAA (28.45%). Conclusions: These findings suggest that comprehensive adherence to healthy lifestyle behaviors is associated with reduced epigenetic aging, supporting their potential utility as targets for mortality risk mitigation. And emphasize the utility of epigenetic clocks in precision gerontology. |
| format | Article |
| id | doaj-art-3dfef040d1c24c3f8b10c3e13857b093 |
| institution | Matheson Library |
| issn | 1760-4788 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Journal of Nutrition, Health and Aging |
| spelling | doaj-art-3dfef040d1c24c3f8b10c3e13857b0932025-07-12T04:45:58ZengElsevierThe Journal of Nutrition, Health and Aging1760-47882025-07-01297100602Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adultsXing-Ling Chen0Qiang-Qiang Zhao1Sheng-Rong Lin2Xing-Ling He3Xiao-Jiao Zhang4Si-Jing Li5Zi-Ru Li6Jia-Hui Chen7Hua Zhang8Xiao-Fang Li9Yue-Hui Zhou10Hui-Li Liao11Shu-Ning Sun12Zhong-Qi Yang13Shi-Hao Ni14Lu Lu15The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, ChinaThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, China; Corresponding authors.The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, China; Corresponding authors.The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, China; Corresponding authors.The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Guangdong Clinical Research Institute of Chinese Medicine, Guangzhou 510407, China; Corresponding authors.Background: The impact of healthy lifestyles on epigenetic age acceleration (EAA) and mortality in middle-aged/ senior populations remains unclear. This study investigates associations between lifestyle factors, EAA biomarkers, and mortality risk. Method: The 2532 adults of 50 years or older that registered in NHANES between 1999–2002.This study evaluated compares first- to third-generation epigenetic clocks (HannumAge, HorvathAge, PhenoAge, GrimAge2, DunedinPoAm) in predicting mortality risk associations between five lifestyle domains (diet, abdominal adiposity, physical activity, smoking, alcohol) and EAA were analyzed via multivariable regression, with mediation models testing EAA’s role in lifestyle-mortality relationships. Results: Survival curves results identified DunedinPoAm, GrimAge2AA, and PhenoAgeAA as robust biomarkers of accelerated biological aging, independent of chronological age. In multivariable linear regression models, full adherence to healthy behaviors reduced GrimAge2AA by β = −5.55 years, PhenoAgeAA by β = −2.64 years, and DunedinPoAm by β = −0.06 SD, with smoking cessation demonstrating the strongest GrimAge2AA attenuation (10.17 years). Stratified analyses revealed pronounced benefits: cancer patients adhering to healthy diets (β = −0.04 SD, P for interaction = 0.01) and hypertensive individuals reducing smoking (β = −0.05 SD, P for interaction = 0.04) showed significant EAA mitigation. The sensitivity analysis is consistent with the original results. Mediation analyses indicated GrimAge2AA accounted for 63.58% of lifestyle-survival associations, DunedinPoAm (44.63%) and PhenoAgeAA (28.45%). Conclusions: These findings suggest that comprehensive adherence to healthy lifestyle behaviors is associated with reduced epigenetic aging, supporting their potential utility as targets for mortality risk mitigation. And emphasize the utility of epigenetic clocks in precision gerontology.http://www.sciencedirect.com/science/article/pii/S1279770725001277Biological agingEpigenetic age accelerationHealthy dietSmokingDrinking |
| spellingShingle | Xing-Ling Chen Qiang-Qiang Zhao Sheng-Rong Lin Xing-Ling He Xiao-Jiao Zhang Si-Jing Li Zi-Ru Li Jia-Hui Chen Hua Zhang Xiao-Fang Li Yue-Hui Zhou Hui-Li Liao Shu-Ning Sun Zhong-Qi Yang Shi-Hao Ni Lu Lu Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adults The Journal of Nutrition, Health and Aging Biological aging Epigenetic age acceleration Healthy diet Smoking Drinking |
| title | Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adults |
| title_full | Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adults |
| title_fullStr | Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adults |
| title_full_unstemmed | Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adults |
| title_short | Epigenetic clocks as mediators of health behaviors and mortality in middle-aged and older adults |
| title_sort | epigenetic clocks as mediators of health behaviors and mortality in middle aged and older adults |
| topic | Biological aging Epigenetic age acceleration Healthy diet Smoking Drinking |
| url | http://www.sciencedirect.com/science/article/pii/S1279770725001277 |
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