Relationship of healthy lifestyle with healthy aging and the mediation by plasma proteins: a prospective cohort study

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 a 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 y 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 7 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 was assessed.

Results: A total of 16,269 participants achieved healthy aging. Compared with 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 a healthy lifestyle, largely involving the pathways associated with immune-inflammatory responses and lipid metabolism and atherosclerosis. There were 26 proteins that 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%-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.

Keywords: UK Biobank; cohort study; healthy aging; healthy lifestyle; proteomics.