Profiling lgG N-glycans as biomarkers of the ageing process: The Busselton Healthy Ageing Study

Project Outline:

A global rise in life expectancy comes with an increased burden of serious life-long health issues and the need for useful real-time indicators of the ageing process. We propose to investigate the value of biochemical profiles of lgG N-glycosylation in blood as clinically relevant biomarkers to differentiate healthy from accelerated ageing over a 25-year period in the well-characterised existing Australian cohort of the Busselton Healthy Ageing Study (B HAS). Most human biological processes rely on N-glycosylation of proteins to regulate their function, but these events appear sensitive to environmental changes, age and the presence of disease. Specifically, variations in N-glycosylation of lgG can adversely affect inflammatory pathways underpinning unhealthy ageing and chronic disease pathogenesis. We have previously shown in several European and Chinese population cohorts that lgG N-glycan profiles can serve as dynamic indicators of ageing, able to discriminate between normal and accelerated ageing by highlighting a discrepancy between a body's age in years of life (chronological age) and its age in terms of health status (biological age). We have also revealed that selective combinations of lgG N-glycan structures associate with biological hallmarks of pre-chronic disease states when biological age precedes chronological age, and we have verified the validity of these lgG N-glycan combinations as predictive risk profiles of unhealthy biological ageing in these international cohorts. This study will now address the usefulness of lgG N-glycan profiles as real-time indicators of ageing among Australians by (i) studying lgG N-glycosylation retro- and prospectively in BHAS, (ii) capturing the influences of genetics, environment and time on lgG N-glycosylation in BHAS, and (ii) validating newly discovered lgG N-glycan risk profiles by comparing them to available findings from African, Chinese and European cohorts previously established for a similar   purpose.

Research Questions:

lgG N- glycan profiles present as real-time indicators of the interaction between genetic predisposition and the environment. lgG N- glycans serve as predictive biomarkers when health is evaluated in the context of age, based on the proposition that specific lgG N-glycans:

1. Identify variations in responses to maturation, ageing, and environment across the life course at a population level
2. Facilitate early risk prediction of chronic disease development
3. Serve as prognostic indicators for the benefit of targeted preventative and disease treatment interventions.

Project Area: Medical Science

School / Research Centre / Institute: Centre for Precision Health

Supervisor:  Professor Wei Wang