Biological Age Estimation Using Circulating Blood Biomarkers

ABSTRACT

Biological Age (BA) captures physiological deterioration better than chronological age and is amenable to interventions. Blood-based biomarkers have been identified as suitable candidates for BA estimation. This study aims to improve BA estimation using machine learning models and a feature-set of 60 circulating biomarkers available from the UK Biobank (UKBB) (n = 307,000). We implement an Elastic-Net derived Cox model with 25 selected biomarkers to predict mortality risk, which outperforms the well-known blood-biomarker based PhenoAge model, providing a 9.2% relative increase in predictive value. Importantly, we then show that using common clinical assay panels, with few biomarkers, alongside imputation and the model derived on the full set of biomarkers, does not substantially degrade predictive accuracy from the theoretical maximum achievable for the available biomarkers. BA is estimated as the equivalent age within the same-sex population which corresponds to an individual’s mortality risk. Values ranged between 20-years younger and 20-years older than individuals’ chronological age, exposing the magnitude of ageing signals contained in blood markers. Thus, we demonstrate a practical and cost-efficient method of estimating an improved measure of BA, available to the general population.

Competing Interest Statement

PKJ and JB are paid consultants to Humanity Inc, a company focussed on measuring and developing interventions for Biological Age. LK is an employee of Humanity Inc. AG was formerly a paid consultant of Humanity Inc. MG and PW are founders of Humanity Inc and are employees and hold ordinary shares. PKJ, LK, MG and PW are partly remunerated under a Humanity Inc share option scheme. PKJ is founder of Geromica, a consultancy providing advice on measurement of health and aging. MC-H holds shares in the O-SMOSE company and has no conflict of interest to disclose. Consulting activities conducted by the company are independent of the present work.

Funding Statement

This study was partly funded by Humanity Inc, a company dedicated to measuring and improving biological age. JB was supported by a Commonwealth Scholarship at Imperial College London, funded by the UK Foreign, Commonwealth & Development Office (FCDO). DV and MC-H are members of the Health Protection Research Unit in Chemical and Radiation Threats and Hazards, a partnership between Public Health England and Imperial College London which is funded by the National Institute for Health Research (NIHR). Neither the FCDO nor the NIHR had a role in the study design, data analysis, preparation of manuscript or decision to publish.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

UK Biobank has approval from the North West Multi-centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB) approval. This approval means that researchers do not require separate ethical clearance and can operate under the RTB approval. UK Biobank gave ethical approval for this work under application number 69634.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

The data used for this study is available to all qualified researchers via the UK Biobank data access process.

https://www.ukbiobank.ac.uk/

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