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


Maximus Peto’s Commentary

These two biomarkers–pentosidine and D-aspartic acid–were able to predict chronological age with a mean absolute error of 4.0 years in this study. This seems interesting (I had never heard until now that D-aspartate accumulates during the lifespan), but these seem like biomarkers that might be “gamed” or “fooled” relatively easily by interventions that would affect the biomarker, but not the level of system-wide biological damage in the organism. The same idea holds true for other “aging biomarkers” such as testosterone, IGF-1, and DHEA-S. I wonder what others think of this report.


Age estimation based on different molecular clocks in several tissues and a multivariate approach: an explorative study.
Int J Legal Med. 2020 Mar;134(2):721-733.
Becker J, Mahlke NS, Reckert A, Eickhoff SB, Ritz-Timme S
DOI: 10.1007/s00414-019-02054-9
PubMed publication date (edat): 4/13/2019

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.

PMID: 30976985
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Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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