The mouse metallomic landscape of aging and metabolism

The metallome is crucial for normal cell functioning but remains largely overlooked in mammals. Here the authors analyze the metallome and copper and zinc isotope compositions in aging mice and show networks of interactions that are organ-specific, age-dependent, isotopically-typified and associated with a wealth of clinical and molecular traits. 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.

Automated summary

The metallome is often overlooked in mammals, but it plays a crucial role in cell functioning. In this study, the authors analyze the metallome and copper and zinc isotope compositions in aging mice and identify organ-specific, age-dependent, and isotopically-typified networks of interactions that are associated with clinical and molecular traits. The findings shed light on the importance of the metallome as an overlooked omic layer and provide insights into potential manipulation of cellular processes.