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Age estimation based on different molecular clocks in several tissues and a multivariate approach: an explorative study

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Abstract

Several molecular modifications accumulate in the human organism with increasing age. Some of these “molecular clocks” in DNA and in proteins open up promising approaches for the development of methods for forensic age estimation. A natural limitation of these methods arises from the fact that the chronological age is determined only indirectly by analyzing defined molecular changes that occur during aging. These changes are not linked exclusively to the expired life span but may be influenced significantly by intrinsic and extrinsic factors in the complex process of individual aging. We tested the hypothesis that a combined use of different molecular clocks in different tissues results in more precise age estimates because this approach addresses the complex aging processes in a more comprehensive way. Two molecular clocks (accumulation of d-aspartic acid (d-Asp), accumulation of pentosidine (PEN)) in two different tissues (annulus fibrosus of intervertebral discs and elastic cartilage of the epiglottis) were analyzed in 95 cases, and uni- and multivariate models for age estimation were generated. The more parameters were included in the models for age estimation, the smaller the mean absolute errors (MAE) became. While the MAEs were 7.5–11.0 years in univariate models, a multivariate model based on the two protein clocks in the two tissues resulted in a MAE of 4.0 years. These results support our hypothesis. The tested approach of a combined analysis of different molecular clocks analyzed in different tissues opens up new possibilities in postmortem age estimation. In a next step, we will add the epigenetic clock (DNA methylation) to our protein clocks (PEN, d-Asp) and expand our set of tissues.

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  1. Julia Becker and Nina Mahlke contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Institute of Legal Medicine, University Hospital Düsseldorf, 40225, Dusseldorf, Germany

    Julia Becker, Nina Sophia Mahlke, A. Reckert & S. Ritz-Timme

  2. Institute for Systems Neuroscience, University Hospital Düsseldorf, 40225, Dusseldorf, Germany

    S. B. Eickhoff

  3. Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, 52428, Julich, Germany

    S. B. Eickhoff

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  1. Julia Becker
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Correspondence to Nina Sophia Mahlke.

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All procedures performed in studies involving human tissue were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (approved by Ethics Committee at the Medical Faculty of Heinrich-Heine University: 6191R, 3667). This article does not contain any studies with animals performed by any of the authors.

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Becker, J., Mahlke, N.S., Reckert, A. et al. Age estimation based on different molecular clocks in several tissues and a multivariate approach: an explorative study. Int J Legal Med 134, 721–733 (2020). https://doi.org/10.1007/s00414-019-02054-9

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