Relationship of healthy lifestyle with healthy aging and the mediation by plasma proteins: a prospective cohort study
The American Journal of Clinical Nutrition, 2025
Fang F., Liu Z., Lyu J., Miao M., Gu J., Qian Y., Shao X., Wan Z., Qin L., Yang J., Cai X., Fang Q., Chen G.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Aging | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Background
Lifestyle factors have been widely associated with various major chronic diseases (MCDs) and life expectancy.
Objectives
Our study aimed to investigate the relationship of healthy lifestyle with the odds of healthy aging and the mediating role of plasma proteins.
Methods
We included 26,774 participants from UK Biobank aged 64 years or older who were free of 15 MCDs at baseline. Healthy aging was defined as survival to age 80 without developing MCDs at the end of follow-up. According to a composite score of seven lifestyle factors, the participants were grouped as having healthy (6 or 7 healthy lifestyle factors), intermediate (3-5 healthy lifestyle factors), or unhealthy (0-2 healthy lifestyle factors) lifestyles. Multivariable logistic regression models were used to evaluate the association of lifestyle categories with the odds of healthy aging. In a subsample (n = 3231), proteomic signatures of healthy lifestyle were identified and their potential mediation on the relationship of healthy lifestyle with healthy aging were assessed.
Results
A total of 16,269 participants achieved healthy aging. Compared to an unhealthy lifestyle, a healthy lifestyle was associated with 117% (95% CI: 95%-141%) higher odds of healthy aging, as well as lower risks of all-cause mortality and various MCDs. There were 879 plasma proteins associated with healthy lifestyle, largely involving the pathways associated with immune-inflammatory responses and lipid metabolism and atherosclerosis. There were 26 proteins which had the strongest correlations with healthy lifestyle (absolute value of effect size >0.15), among which 13 proteins were found to significantly explain 10.9% to 30.7% of the relationship between healthy lifestyle and healthy aging. Fatty acid-binding protein 4, adrenomedullin, and hepatocyte growth factor were the leading mediators.
Conclusions
A healthy lifestyle is associated with substantially higher odds of healthy aging, potentially through the regulation of specific circulating proteins.