The mouse metallomic landscape of aging and metabolism

Jean-David Morel, Lucie Sauzéat, Ludger J. E. Goeminne, Pooja Jha, Evan Williams, Riekelt H. Houtkooper, Ruedi Aebersold, Johan Auwerx () and Vincent Balter ()
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Jean-David Morel: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne
Lucie Sauzéat: Université de Lyon, Ecole Normale Supérieure de Lyon, Université de Lyon 1, CNRS, LGL-TPE
Ludger J. E. Goeminne: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne
Pooja Jha: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne
Evan Williams: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne
Riekelt H. Houtkooper: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne
Ruedi Aebersold: Institute of Molecular Systems Biology, ETH Zürich
Johan Auwerx: Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne
Vincent Balter: Université de Lyon, Ecole Normale Supérieure de Lyon, Université de Lyon 1, CNRS, LGL-TPE

Nature Communications, 2022, vol. 13, issue 1, 1-8

Abstract: Abstract Organic elements make up 99% of an organism but without the remaining inorganic bioessential elements, termed the metallome, no life could be possible. The metallome is involved in all aspects of life, including charge balance and electrolytic activity, structure and conformation, signaling, acid-base buffering, electron and chemical group transfer, redox catalysis energy storage and biomineralization. Here, we report the evolution with age of the metallome and copper and zinc isotope compositions in five mouse organs. The aging metallome shows a conserved and reproducible fingerprint. By analyzing the metallome in tandem with the phenome, metabolome and proteome, we show networks of interactions that are organ-specific, age-dependent, isotopically-typified and that are associated with a wealth of clinical and molecular traits. We report that the copper isotope composition in liver is age-dependent, extending the existence of aging isotopic clocks beyond bulk organic elements. Furthermore, iron concentration and copper isotope composition relate to predictors of metabolic health, such as body fat percentage and maximum running capacity at the physiological level, and adipogenesis and OXPHOS at the biochemical level. Our results shed light on the metallome as an overlooked omic layer and open perspectives for potentially modulating cellular processes using careful and selective metallome manipulation.

Date: 2022
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DOI: 10.1038/s41467-022-28060-x

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