Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

From Immunosenescence to Aging Types – Establishing Reference Intervals for Immune Age Biomarkers by Centile Estimation

Peter Bröde
* ORCID logo ,
Maren Claus
,
Patrick D Gajewski
ORCID logo ,
Stephan Getzmann
ORCID logo ,
Edmund Wascher
ORCID logo ,
Carsten Watzl
ORCID logo
Version 1 : Received: 3 August 2023 / Approved: 4 August 2023 / Online: 7 August 2023 (10:05:00 CEST)

A peer-reviewed article of this Preprint also exists.

Bröde, P.; Claus, M.; Gajewski, P.D.; Getzmann, S.; Wascher, E.; Watzl, C. From Immunosenescence to Aging Types—Establishing Reference Intervals for Immune Age Biomarkers by Centile Estimation. Int. J. Mol. Sci. 2023, 24, 13186. Bröde, P.; Claus, M.; Gajewski, P.D.; Getzmann, S.; Wascher, E.; Watzl, C. From Immunosenescence to Aging Types—Establishing Reference Intervals for Immune Age Biomarkers by Centile Estimation. Int. J. Mol. Sci. 2023, 24, 13186.

Abstract

Immunological aging type definition requires establishing reference intervals from the distribution of immunosenescence biomarkers conditional on age. For 1,605 individuals (18–97 years), we determined the comprehensive IMMmune Age indeX IMMAX from flow cytometry-based blood cell sub-populations, and identified age-specific centiles by fitting generalized additive models for location, scale and shape. The centiles were uncorrelated with age, and facilitated the categorization of individuals as immunologically slow or fast aging types. Using its 50th percentile as reference, we rescaled IMMAX to equivalent years-of-life (EYOL), and computed the immunological age gap as difference between EYOL and chronological age. Applied to preliminary baseline and follow-up measurements from 53 participants of the Dortmund Vital Study (Clinical-Trials.gov Identifier: NCT05155397), the averaged changes in IMMAX and EYOL conformed to the 5-year follow-up period, whereas no significant changes occurred concerning IMMAX centiles and age gap. This suggested that the participants immunologically adapted to aging, and kept their relative positions within the cohort. Sex was non-significant. Methodical comparisons indicated that future confirmatory analyses with the completed follow-up examinations could rely on percentile curves estimated by simple linear quantile regression, while the selection of the immunosenescence biomarker will greatly influence the outcome, with IMMAX representing the preferable choice.

Keywords

immunosenescence; biological age; biomarker; flow cytometry; longitudinal study

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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