Combining blood biochemistry and glycan ages for an even more prognostic biological age

Abstract Glycan- and blood marker–based biological ages are prognostic of health and survival. However, glycans and haematology measures (as opposed to blood biochemistry) are rarely available together in outcome-based studies. Consequently, no dataset available to us could unify these biological age estimates. We therefore developed a new measure, PlasmaAge, using only biochemistry markers measured in ORCADES but trained within UK Biobank. In ORCADES, PlasmaAge, a glycan-based age, and their composite all predicted mortality, improving AUC over chronological age alone by 0.026, 0.032, and 0.041 respectively. We confirmed these effects on mortality in Croatian cohorts. PlasmaAge provides a new estimate of biological ageing for studies where only biochemistry data are available. Moreover, we show that PlasmaAge and glycan-based age can be combined into a more prognostic composite biological age, suitable for use in both research and commercial settings. Competing Interest Statement The authors declare the following competing interests: during preparation of this manuscript, PKJ and JB were paid consultants to Humanity Inc, a company focussed on measuring and developing interventions for Biological Age. MG and PW are founders of Humanity Inc and are employees and hold ordinary shares. PKJ, 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 ageing. GL is the cofounder and CSO of GlycanAge Ltd. The company that offers the glycan-based test for biological age. All other authors declare no competing interests. Funding Statement This study did not receive any funding. 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: This work used existing datasets (UK Biobank), for which ethical approval (including informed consent) had been obtained by UK Biobank for health investigation at the time of collection. This project was approved under UK biobank project 69634. All participants in Croatian island cohorts signed an informed consent and study was approved by the Ethics Committee of the University of Split Medical School. For ORCADES, all participants gave written informed consent and the study holds favourable opinions from Research Ethics Committees in Orkney, Aberdeen (North of Scotland REC), and South East Scotland REC, NHS Lothian (reference: 12/SS/0151). ORCADES is now part of Viking Genes (https://viking.ed.ac.uk/), under South East Scotland REC, NHS Lothian (reference 19/SS/0104; IRAS 264868). 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). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available from UK Biobank or are available upon reasonable request to the authors