Approved Research

Metabolomic aging in the UK Biobank and CALERIE

Lay summary

Work in animal models, including non-human primates, has shown extensive evidence for increases in lifespan and healthspan following caloric restriction (CR) initiated in adulthood or midlife. The foremost data for the effects of CR in humans comes from the National Institute on Aging sponsored Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy (CALERIE) study. Using data from CALERIE, researchers have provided evidence for significant improvements to cardiometabolic health, liver functioning, and immune health following moderate CR (~12%) over a span of two years.

The mechanisms for how CR improves health remain unclear, with suggested impacts spanning cellular repair, metabolic, and immune processes. One appealing avenue to explore these processes simultaneously is metabolomics, the comprehensive profiling of metabolites in biological material. Metabolomics has been applied to study the biological processes implicated in cancer, cardiovascular disease, and diabetes. Furthermore, the technique has been used to explore changes in the rate of biological aging in the form of a metabolomic age score, interpreted as the chronological age at which an individual's metabolomic index would be approximately normal.

The goal of this data-driven proposal is three-fold. First, we will utilize UK Biobank data to describe trends in metabolomic aging across sociodemographic strata using three different metabolomic age scores. Next, we will investigate the impact of caloric restriction on metabolomic aging by applying each metabolomic age score in the CALERIE study. Lastly, we will scrutinize the metabolites that make up each age score to identify possible biological pathways and mechanisms responsible for the beneficial impacts of caloric restriction on health. In doing so we can reveal novel targets for diagnosis, prevention, and/or treatment for the general population.

The expected duration of the project is two years from data acquisition to publication. The first three months are allotted to organize and clean the UK Biobank data, followed by another three months to construct all measures in the UK Biobank and CALERIE samples. The remainder of the first year will be used to conduct analyses, and the second year will be used to write up and publish results with consultation from co-authors.