Research Question: How does proteomic age acceleration (PAA) mediate the relationship between a healthy lifestyle and the development of multimorbidity, and what is its role in mortality outcomes following multimorbidity?
Aims: (1)To build and validate a plasma proteomic age clock. (2)To examine the association between a Healthy Lifestyle Index (HLI) and multimorbidity. (3)To investigate the effect of PAA on multimorbidity and mortality. (4)To assess the incremental predictive value of PAA.
Scientific Rationale:Multimorbidity, the coexistence of multiple chronic conditions in an individual, is a growing public health issue worldwide. While the impact of adherence to healthy behaviors on reducing the burden of disease and mortality is well-established, the biological mechanisms linking lifestyle factors to clinical outcomes remain poorly understood. The circulating proteome, a complex collection of proteins found in blood plasma, reflects various biological processes, including inflammation, metabolism, immune responses, and extracellular matrix remodeling, all of which contribute to aging and disease progression. Proteomic age acceleration (PAA) represents the deviation of an individual’s biological age from their chronological age. This deviation can offer insight into the accelerated biological aging process and multisystem wear-and-tear that often underpins the development of multimorbidity. PAA has the potential to serve as a more sensitive biomarker of aging than chronological age alone, providing a clearer picture of biological vulnerability that may predispose individuals to chronic diseases and poor health outcomes. Leveraging UK Biobank data available, this study aims to unravel the role of PAA in mediating the impact of healthy lifestyle behaviors on the development of multimorbidity and mortality.
